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Sample records for site antibody b12

  1. A radioisotope dilution assay for unlabelled vitamin B12-intrinsic factor complex employing the binding intrinsic factor antibody: probable evidence for two types of binding antibody

    International Nuclear Information System (INIS)

    Jacob, E.; O'Brien, H.A.W.; Mollin, D.L.

    1977-01-01

    A new radioisotope dilution assay for vitamin B 12 -intrinsic factor complex is described. The method is based on the use of the binding type intrinsic antibody (the binding reagent), which when combined with the intrinsic factor-vitamin B 12 complex (labelled ligand), is quantitatively adsorbed onto zirconium phosphate gel pH 6.25. The new assay has been shown to provide a measure of intrinsic factor comparable with other intrinsic factor assays, but it has the important advantage of being able to measure the unlabelled vitamin B 12 -intrinsic factor complex (unlabelled ligand), and will, therefore, be valuable in the study of physiological events in the gastrointestinal tract. During the study, it was found that there is some evidence for at least two types of binding intrinsic factor antibody: One which combines preferentially with the intrinsic factor-vitamin B 12 complex and one which combines equally well with this complex or with free intrinsic factor. (author)

  2. An assay for serum vitamin-B12 and for intrinsic factor antibody type I by means of hog intrinsic factor

    International Nuclear Information System (INIS)

    Hudak, J.; Berger, Z.; Varga, L.

    1980-01-01

    A new radioassay method was elaborated for the determination of the plasma level of vitamin B 12 and of the intrinsic factor antibody type I. The assay applies vitamin-B 12 labelled with 58 Co, but replaces human intrinsic factor by hog intrinsic factor. 124 cases were investigated by both the original and this modified method, and the results were in very good agreement. (L.E.)

  3. Binding site for the adenosyl group of coenzyme B12 in diol dehydrase

    International Nuclear Information System (INIS)

    Toraya, T.

    1985-01-01

    The binding of cob(II)alamin (CblII) and 5'-deoxyadenosine to diol dehydrase was studied spectroscopically and with [U- 14 C]5'-deoxyadenosine. CblII was bound to this enzyme forming a tight 1:1 complex which was resistant to oxidation by O 2 even in the presence of CN-. An irreversible 1:1:1 ternary complex was formed between enzyme, CblII, and 5'-deoxyadenosine, when the enzyme was incubated first with the nucleoside and then with CblII. When this order of addition of the constituents was reversed, no 5'-deoxyadenosine was bound to the enzyme-CblII complex. Hydroxocobalamin could also bind to the enzyme together with the nucleoside, while other cob(III)alamins bearing a bulkier Co beta ligand displaced the nucleoside upon binding to the enzyme. The binding of [U- 14 C]5'-deoxyadenosine was strongly inhibited by unlabeled 5'-deoxy-ara-adenosine, 4',5'-anhydroadenosine, adenosine, adenine, and 5',8-cyclic adenosine, in this order, but not by 5'-deoxyuridine. These results constitute direct evidence for the presence of the binding site for the adenosyl group of adenosylcobalamin, which is spatially limited to and highly specific for adenine nucleosides. The binding of 5'-deoxyadenosine to the apoenzyme was reversible

  4. Vitamin B12

    Science.gov (United States)

    ... Consumer Datos en español Health Professional Other Resources Vitamin B12 Fact Sheet for Consumers Have a question? ... out more about vitamin B12? Disclaimer What is vitamin B12 and what does it do? Vitamin B12 ...

  5. Vitamin B12 deficiency

    Science.gov (United States)

    Vitamin B12 (B12; also known as cobalamin) is a B vitamin that has an important role in cellular metabolism, especially in DNA synthesis, methylation and mitochondrial metabolism. Clinical B12 deficiency with classic haematological and neurological manifestations is relatively uncommon. However, sub...

  6. Vitamin B-12

    Science.gov (United States)

    Vitamin B-12 is a cofactor for 2 enzymes. In the cytoplasm, methionine synthase requires vitamin B-12 in the form of methylcobalamin and catalyzes the conversion of homocysteine to methionine by transfer of a methyl group from methyltetrahydrofolate.This enzyme links the methylation pathway through ...

  7. Vitamin B12 deficiency

    DEFF Research Database (Denmark)

    Green, Ralph; Allen, Lindsay H; Bjørke-Monsen, Anne-Lise

    2017-01-01

    , subclinical deficiency affects between 2.5% and 26% of the general population depending on the definition used, although the clinical relevance is unclear. B12 deficiency can affect individuals at all ages, but most particularly elderly individuals. Infants, children, adolescents and women of reproductive age...... remain debated. Management depends on B12 supplementation, either via high-dose oral routes or via parenteral administration. This Primer describes the current knowledge surrounding B12 deficiency, and highlights improvements in diagnostic methods as well as shifting concepts about the prevalence, causes...

  8. Vitamin B12

    Science.gov (United States)

    Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academies Press. Washington, DC, 1998. PMID: 23193625 ...

  9. Radioactively labelled vitamin B12

    International Nuclear Information System (INIS)

    Charlton, J.C.; Hamilton, A.L.

    1978-01-01

    The application concerns the manufacture of radioactive forms of vitamin B-12 in which the cobalt atom present in the vitamin B-12 molecule is replaced with a radioactive isotope of cobalt, usually cobalt-57 or cobalt-58. Such radioactive forms of B-12 are used extensively in the diagnosis of B-12 deficiency states

  10. Polyvalent immunoglobulins with vitamin D3 and vitamin B12 in the treatment of Sjogren's syndrome in a vegetarian with stomatitis, glossodynia, xerostomia, and elevated antinuclear antibodies: Case report
.

    Science.gov (United States)

    Cuny, Clemens; Vaerst, Barbara; Gabrielpillai, Jennis; Tahtali, Aykut; Balster, Sven; Lissner, Reinhard; Woodcock, Barry G

    2018-01-01

    Sjogren's syndrome, involving sicca symptoms with xerostomia, stomatitis, and considerable pain is a difficult-to-treat autoimmune disease where the treatment options are limited and, as in the case of methotrexate, have a low therapeutic index. This case report concerns a male patient, aged 75 years and vegetarian, with Sjogren's syndrome subsequently confirmed by salivary gland biopsy. Serum antinuclear antibodies (ANA) were elevated (1 : 320). Low serum vitamin B12 and iron levels could be improved after 20 days using vitamin B12 and iron oral supplements. Despite symptomatic treatment, xerostomia, glossitis, and glossodynia were still present, at times marked, after 12 months when the ANA titer was unchanged. Following treatment with an anti-inflammatory polyvalent immunoglobulin formulation (Lactobin®N, 7 g daily), a bovine colostrum concentrate given orally in combination with oral vitamin D3 (2,000 IU daily), sicca symptoms and xerostomia progressively decreased and at day 750 were confined to occasional and minor glossitis of the upper lip. This case report demonstrates the satisfactory control of Sjogren's syndrome using oral polyvalent immunoglobulins with vitamin D3. In contrast to treatment options involving antimalarial drugs and methotrexate, there are no safety issues in patients tolerant to milk products.
.

  11. Organometallic B12-DNA conjugate

    DEFF Research Database (Denmark)

    Hunger, Miriam; Mutti, Elena; Rieder, Alexander

    2014-01-01

    Design, synthesis, and structural characterization of a B12-octadecanucleotide are presented herein, a new organometallic B12-DNA conjugate. In such covalent conjugates, the natural B12 moiety may be a versatile vector for controlled in vivo delivery of oligonucleotides to cellular targets in hum...

  12. Genetic and non-genetic influences during pregnancy on infant global and site specific DNA methylation: role for folate gene variants and vitamin B12.

    Directory of Open Access Journals (Sweden)

    Jill A McKay

    Full Text Available Inter-individual variation in patterns of DNA methylation at birth can be explained by the influence of environmental, genetic and stochastic factors. This study investigates the genetic and non-genetic determinants of variation in DNA methylation in human infants. Given its central role in provision of methyl groups for DNA methylation, this study focuses on aspects of folate metabolism. Global (LUMA and gene specific (IGF2, ZNT5, IGFBP3 DNA methylation were quantified in 430 infants by Pyrosequencing®. Seven polymorphisms in 6 genes (MTHFR, MTRR, FOLH1, CβS, RFC1, SHMT involved in folate absorption and metabolism were analysed in DNA from both infants and mothers. Red blood cell folate and serum vitamin B(12 concentrations were measured as indices of vitamin status. Relationships between DNA methylation patterns and several covariates viz. sex, gestation length, maternal and infant red cell folate, maternal and infant serum vitamin B(12, maternal age, smoking and genotype were tested. Length of gestation correlated positively with IGF2 methylation (rho = 0.11, p = 0.032 and inversely with ZNT5 methylation (rho = -0.13, p = 0.017. Methylation of the IGFBP3 locus correlated inversely with infant vitamin B(12 concentration (rho = -0.16, p = 0.007, whilst global DNA methylation correlated inversely with maternal vitamin B(12 concentrations (rho = 0.18, p = 0.044. Analysis of common genetic variants in folate pathway genes highlighted several associations including infant MTRR 66G>A genotype with DNA methylation (χ(2 = 8.82, p = 0.003 and maternal MTHFR 677C>T genotype with IGF2 methylation (χ(2 = 2.77, p = 0.006. These data support the hypothesis that both environmental and genetic factors involved in one-carbon metabolism influence DNA methylation in infants. Specifically, the findings highlight the importance of vitamin B(12 status, infant MTRR genotype and maternal MTHFR genotype, all of which may influence the supply of methyl groups for

  13. S100A4-neutralizing antibody suppresses spontaneous tumor progression, pre-metastatic niche formation and alters T-cell polarization balance

    DEFF Research Database (Denmark)

    Grum-Schwensen, Birgitte; Klingelhöfer, Jörg; Beck, Mette

    2015-01-01

    , decreased vessel density and inhibition of metastases. CONCLUSION: The S100A4 blocking antibody (6B12) reduces tumor growth and metastasis in a model of spontaneous breast cancer. The 6B12 antibody treatment inhibits T cell accumulation at the primary and pre-metastatic tumor sites. The 6B12 antibody acts...

  14. Vitamin B12 deficiency anemia

    Science.gov (United States)

    ... diet Poor diet in infants Poor nutrition during pregnancy Certain health conditions can make it difficult for your body to absorb enough vitamin B12. They include: Chronic alcoholism Crohn disease, celiac disease, infection with the fish ...

  15. Assay of vitamin B12

    International Nuclear Information System (INIS)

    Tovey, K.C.; Carrick, D.T.

    1982-01-01

    A radioassay is described for vitamin B12 which involves denaturing serum protein binding proteins with alkali. In the denaturation step a dithiopolyol and cyanide are used and in the intrinsic factor assay step a vitamin B12 analogue such as cobinamide is used to bind with any remaining serum proteins. The invention also includes a kit in which the dithiopolyol is provided in admixture with the alkali. The dithiopolyol may be dithiothreitol or dithioerythritol. (author)

  16. Distance between two binding sites of the same antibody molecule

    International Nuclear Information System (INIS)

    Cser, L.; Gladkikh, I.A.; Ostanevich, Y.M.; Franek, F.; Novotny, J.; Nezlin, R.S.

    1978-01-01

    Neutron small-angle scattering experiments are reported, aimed at determining the distance between the two binding sites of the same antibody molecule employing complexes of anti-Dnp antibody with an antigenically univalent, high molecular weight ligand. Although the distance values could be determined only with a large statistical error, the data allowed the conclusion that the geometrical parameters of the complexes formed with the early (i.e., precipitating) antibody are significantly different from those of the complexes formed with the late (i.e, non-precipitating) antibody. The data suggest that the precipitating antibody complexed with a high molecular weight antigen assumes an extended shape with an antigen to antigen distance of 35.8 +- 1.3 nm. (Auth.)

  17. Radioactively labelled vitamin B12

    Energy Technology Data Exchange (ETDEWEB)

    Charlton, J C; Lewis, A

    1976-12-01

    A method is described for preparing radioactively labelled vitamin B 12 (cyanocobalamin) by reacting ..cap alpha..-(5,6-dimethylbenzimidazolyl) hydrogenobamide with active (sup(57,58)Co) cobaltous ion. The latter may be in the form of cobaltous chloride or sulphate in aqueous or aqueous alcoholic medium. The reaction is effected by heating the reactants in darkness at pH 4 to 8. An excess of cyanide is added to convert the hydroxocobalamin formed to cyanocobalamin.

  18. Radioactively labelled vitamin B12

    International Nuclear Information System (INIS)

    Charlton, J.C.; Lewis, A.

    1976-01-01

    A method is described for preparing radioactively labelled vitamin B 12 (cyanocobalamin) by reacting α-(5,6-dimethylbenzimidazolyl) hydrogenobamide with active (sup(57,58)Co) cobaltous ion. The latter may be in the form of cobaltous chloride or sulphate in aqueous or aqueous alcoholic medium. The reaction is effected by heating the reactants in darkness at pH 4 to 8. An excess of cyanide is added to convert the hydroxocobalamin formed to cyanocobalamin. (U.K.)

  19. B-12 vitamin metabolism disorders

    International Nuclear Information System (INIS)

    Fabriciova, K.; Bzduch, V.; Behulova, D.; Skodova, J.; Holesova, D.; Ostrozlikova, M.; Schmidtova, K.; Kozich, V.

    2012-01-01

    Vitamin B-12 – cobalamin (Cbl) is a water soluble vitamin, which is synthesized by lower organisms. It cannot be synthesized by plants and higher organisms. Problem in the metabolic pathway of Cbl can be caused by its deficiency or by the deficiency of its last metabolites – adenosylcobalamin and methylcobalamin. Both reasons are presented by errors in the homocysteine and methylmalonyl-coenzyme A metabolism. Clinical symptoms of the Cbl metabolism disorders are: different neurological disorders, changes in haematological status (megaloblastic anemia, pancytopenia), symptoms of gastrointestinal tract (glossitis, loss of appetite, diarrhea) and changes in the immune system. In the article the authors describe the causes of Cbl metabolism disorders, its different diagnosis and treatment. They introduce the group of patients with these disorders, who were taken care of in the I st Paediatric Department of University Children Hospital for the last 5 years. (author)

  20. Vitamin B-12 and Perinatal Health.

    Science.gov (United States)

    Finkelstein, Julia L; Layden, Alexander J; Stover, Patrick J

    2015-09-01

    Vitamin B-12 deficiency (importance of adequate vitamin B-12 status periconceptionally and during pregnancy cannot be overemphasized, given its fundamental role in neural myelination, brain development, and growth. Infants born to vitamin B-12-deficient women may be at increased risk of neural tube closure defects, and maternal vitamin B-12 insufficiency (pregnancy complications, few prospective studies and, to our knowledge, only 1 randomized trial have examined the effects of vitamin B-12 supplementation during pregnancy. The role of vitamin B-12 in the etiology of adverse perinatal outcomes needs to be elucidated to inform public health interventions. © 2015 American Society for Nutrition.

  1. Site-Specific Antibody Functionalization Using Tetrazine-Styrene Cycloaddition.

    Science.gov (United States)

    Umlauf, Benjamin J; Mix, Kalie A; Grosskopf, Vanessa A; Raines, Ronald T; Shusta, Eric V

    2018-05-03

    Biologics, such as antibody-drug conjugates, are becoming mainstream therapeutics. Consequently, methods to functionalize biologics without disrupting their native properties are essential for identifying, characterizing, and translating candidate biologics from the bench to clinical practice. Here, we present a method for site-specific, carboxy-terminal modification of single-chain antibody fragments (scFvs). ScFvs displayed on the surface of yeast were isolated and functionalized by combining intein-mediated expressed protein ligation (EPL) with inverse electron-demand Diels-Alder (IEDDA) cycloaddition using a styrene-tetrazine pair. The high thiol concentration required to trigger EPL can hinder the subsequent chemoselective ligation reactions; therefore, the EPL reaction was used to append styrene to the scFv, limiting tetrazine exposure to damaging thiols. Subsequently, the styrene-functionalized scFv was reacted with tetrazine-conjugated compounds in an IEDDA cycloaddition to generate functionalized scFvs that retain their native binding activity. Rapid functionalization of yeast surface-derived scFv in a site-directed manner could find utility in many downstream laboratory and preclinical applications.

  2. 7 CFR 15b.12 - Discrimination prohibited.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Discrimination prohibited. 15b.12 Section 15b.12... ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Employment Practices § 15b.12 Discrimination prohibited. (a... discrimination in employment under any program or activity receiving assistance from this Department. (2) A...

  3. Fuzzy modeling for Vitamin B12 deficiency

    NARCIS (Netherlands)

    Wilbik, A.M.; van Loon, S.L.M.; Boer, A.K.; Kaymak, U.; Scharnhorst, V.; Carvalho, J.; Lesot, M.J.; Kaymak, U.; Vieira, S.; Bouchon-Meunier, B.; Yager, R.

    2016-01-01

    Blood vitamin B12 levels are not representative for actual vitamin B12 status in tissue. Instead plasma methylmalonic acid (MMA) levels can be measured because MMA concentrations increase relatively early in the course of vitamin B12 deficiency. However, MMA levels in plasma may also be increased

  4. Radioassay of vitamin B-12 employing bentonite

    International Nuclear Information System (INIS)

    Lewin, N.; Fries, J.E.; Richards, C.S.

    1976-01-01

    Radioassay for vitamin B-12 using the unknown quantity of non-radioactive vitamin B-12 released from serum mixed with the radioactivity of a known quantity of radioactive vitamin B-12 tracer. A solution of intrinsic factor having a binding capacity less than the quantity of serum vitamin B-12 and radioactive vitamin B-12 is used to bind a portion of the vitamin B-12 mixture. The vitamin B-12 not bound to intrinsic factor is removed by addition of a bentonite-containing tablet. The quantity of radioactive vitamin B-12 bound to intrinsic factor is compared with standard values and the unknown serum vitamin B-12 obtained. In the steps of the procedure the acid assay medium is pre-combined with the radioactive tracer so that the radioactive vitamin B-12 tracer receives the same treatment as serum vitamin B-12. Certain of the other reagent solutions are pre-combined and the concentration of the components adjusted so that the volume used of each of these other reagent solutions is the same in different assay steps. Thus, fewer pipetting steps are necessary. 7 claims, 1 drawing figure

  5. The EGG 57-CO B-12 absorption test, in the evaluation of patients with low serum B-12

    International Nuclear Information System (INIS)

    Sinow, R.M.; Carmel, R.; Siegel, M.E.

    1985-01-01

    The Schilling Test (ST) is the standard test for diagnosing vitamin B-12 malabsorption (MA). However, patients with subtle gastric dysfunction may have normal ST, but impaired absorption of B-12 given with food. The authors have adapted an Egg B-12 Absorption Test (EBAT) in which 57-Co cyanocobalamin (57-Co B-12) is mixed with scrambled egg to evaluate this phenomenon in patients with low serum B-12, normal ST and possible subtle MA. Lyophilized egg yolk is reconstituted and mixed with 57-Co- B-12 of equal dose to that of ST. The authors studied 46 individuals: 13 controls, 5 patients with known pernicious anemia (PA), in addition to 28 patients with low serum B-12 levels and normal ST. ST/EBAT ratios were calculated. Twenty-eight test patients excreted 13.3% on ST and 3.5% on EBAT. Mean ST/EBAT ratio was 8.2 (1.4-35.9). Five had EBAT results in the PA range (<1%) and ST/EBAT ratios (14.4-35.9) that were significantly elevated. This group is also evaluated with pepsinogen I/II ratios, gastric analysis, deoxyuridine suppression tests, anti intrinsic factor, and antiparietal cell antibodies. The authors' results indicate that the EBAT can differentiate between PA and non PA patients, and that some patients with low serum B-12 levels and normal ST may, in fact, have subtle MA. The EBAT, combined with ST/EBAT ratio, may provide a means for identifying this group of patients

  6. Vitamin B12 absorption from eggs.

    Science.gov (United States)

    Doscherholmen, A; McMahon, J; Ripley, D

    1975-09-01

    The assimilation of 57Co B12 from in vivo labeled eggs was much inferior to that of a comparable amount of crystalline 57Co B12. Furthermore, the absorption varied with the form in which the eggs were served. Judged by the urinary excretion test and the plasma absorption of radioactivity the average absorption from boiled and fried eggs was more than twice that from scrambled whole eggs, but less than half that absorbed from crystalline 57Co B12.

  7. Atypical B12 Deficiency with Nonresolving Paraesthesia

    Directory of Open Access Journals (Sweden)

    S. Haider

    2013-01-01

    Full Text Available Vitamin B12 deficiency can present with various hematological, gastrointestinal and neurological manifestations. We report a case of elderly female who presented with neuropathy and vitamin B12 deficiency where the final work-up revealed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS. This case suggests that, although POEMS syndrome is a rare entity, it can present with vitamin-B12 deficiency and thus specific work up for early diagnosis of POEMS should be considered in patients with B12 deficiency unresponsive to therapy.

  8. How common is vitamin B-12 deficiency?

    Science.gov (United States)

    Allen, Lindsay H

    2009-02-01

    In considering the vitamin B-12 fortification of flour, it is important to know who is at risk of vitamin B-12 deficiency and whether those individuals would benefit from flour fortification. This article reviews current knowledge of the prevalence and causes of vitamin B-12 deficiency and considers whether fortification would improve the status of deficient subgroups of the population. In large surveys in the United States and the United Kingdom, approximately 6% of those aged > or =60 y are vitamin B-12 deficient (plasma vitamin B-12 life. In developing countries, deficiency is much more common, starting in early life and persisting across the life span. Inadequate intake, due to low consumption of animal-source foods, is the main cause of low serum vitamin B-12 in younger adults and likely the main cause in poor populations worldwide; in most studies, serum vitamin B-12 concentration is correlated with intake of this vitamin. In older persons, food-bound cobalamin malabsorption becomes the predominant cause of deficiency, at least in part due to gastric atrophy, but it is likely that most elderly can absorb the vitamin from fortified food. Fortification of flour with vitamin B-12 is likely to improve the status of most persons with low stores of this vitamin. However, intervention studies are still needed to assess efficacy and functional benefits of increasing intake of the amounts likely to be consumed in flour, including in elderly persons with varying degrees of gastric atrophy.

  9. Vitamin B12 and Folate Test

    Science.gov (United States)

    ... offer the folate test. Can taking too many vitamin B12 and folic acid supplements hurt me? Not usually. Since B12 and folic acid are water-soluble, the body will rid itself of any excess by excreting it in the urine. However, taking ...

  10. [Vitamin B12 deficiency: what's new?].

    Science.gov (United States)

    Braillard, O; Casini, A; Samii, K; Rufenacht, P; Junod, Perron N

    2012-09-26

    Vitamin B12 screening is only recommended among symptomatic patients or in those with risk factors. The main cause of vitamin B12 deficiency is the food cobalamin malabsorption syndrom. Holotranscobalamin is a more reliable marker than cyanocobalamin to confirm vitamin B12 deficiency, but it has not been validated yet in complex situations. An autoimmune gastritis must be excluded in the absence of risk factors but in the presence of a probable deficiency. Oral substitution treatment is effective but requires excellent therapeutic compliance and close follow-up to monitor the response to treatment. It has not yet been studied among patients suffering from severe symptoms, inflammatory bowel disease and ileal resection.

  11. Assay for vitamin B12 absorption and method of making labeled vitamin B12

    Science.gov (United States)

    Anderson, Peter J [Davis, CA; Dueker, Stephen [Davis, CA; Miller, Joshua [Davis, CA; Green, Ralph [Elmacero, CA; Roth, John [Davis, CA; Carkeet, Colleen [Silver Spring, MD; Buchholz,; Bruce, A [Orinda, CA

    2012-06-19

    The invention provides methods for labeling vitamin B12 with .sup.14C, .sup.13C, tritium, and deuterium. When radioisotopes are used, the invention provides for methods of labeling B12 with high specific activity. The invention also provides labeled vitamin B12 compositions made in accordance with the invention.

  12. Monoclonal antibodies to human chorionic gonadotropin and their application to two-site sandwich radioimmunoassay

    International Nuclear Information System (INIS)

    Mizuchi, A.; Iio, M.; Miyachi, Y.

    1984-01-01

    Monoclonal antibodies were prepared against human chorionic gonadotropin (HCG). One monoclonal antibody recognized a conformational determinant expressed only on native HCG molecule and another monoclonal antibody had the specificity for the epitopes located on the β-subunit of HCG. Monoclonal antibodies reacting with different antigenic determinants on the HCG molecule were used to develop a simplified 2-site sandwich radioimmunoassay in which one monoclonal antibody was immobilized and another labeled with 125 iodine. This assay was highly specific for HCG and there was no cross-reactivity with α,β-subunit of HCG, luteinizing hormone and follicle stimulating hormone. (Auth.)

  13. Malabsorption of protein bound vitamin B12.

    OpenAIRE

    Dawson, D W; Sawers, A H; Sharma, R K

    1984-01-01

    Patients with subnormal serum vitamin B12 concentrations were tested for absorption of protein bound vitamin B12 and compared with controls. Absorption of the protein bound vitamin appeared to decrease with increasing age in healthy subjects. Differences between the result of this test and the result of the Schilling test in patients who had undergone gastric surgery were confirmed; such differences were also seen in some patients who had iron deficiency anaemia, an excessive alcohol intake, ...

  14. Vitamin B12 and Semen Quality.

    Science.gov (United States)

    Banihani, Saleem Ali

    2017-06-09

    Various studies have revealed the effects of vitamin B12, also named cobalamin, on semen quality and sperm physiology; however, these studies collectively are still unsummarized. Here, we systematically discuss and summarize the currently understood role of vitamin B12 on semen quality and sperm physiology. We searched the Web of Science, PubMed, and Scopus databases for only English language articles or abstracts from September 1961 to March 2017 (inclusive) using the key words "vitamin B12" and "cobalamin" versus "sperm". Certain relevant references were included to support the empirical as well as the mechanistic discussions. In conclusion, the mainstream published work demonstrates the positive effects of vitamin B12 on semen quality: first, by increasing sperm count, and by enhancing sperm motility and reducing sperm DNA damage, though there are a few in vivo system studies that have deliberated some adverse effects. The beneficial effects of vitamin B12 on semen quality may be due to increased functionality of reproductive organs, decreased homocysteine toxicity, reduced amounts of generated nitric oxide, decreased levels of oxidative damage to sperm, reduced amount of energy produced by spermatozoa, decreased inflammation-induced semen impairment, and control of nuclear factor-κB activation. However, additional research, mainly clinical, is still needed to confirm these positive effects.

  15. Vitamin B12 and Semen Quality

    Directory of Open Access Journals (Sweden)

    Saleem Ali Banihani

    2017-06-01

    Full Text Available Various studies have revealed the effects of vitamin B12, also named cobalamin, on semen quality and sperm physiology; however, these studies collectively are still unsummarized. Here, we systematically discuss and summarize the currently understood role of vitamin B12 on semen quality and sperm physiology. We searched the Web of Science, PubMed, and Scopus databases for only English language articles or abstracts from September 1961 to March 2017 (inclusive using the key words “vitamin B12” and “cobalamin” versus “sperm”. Certain relevant references were included to support the empirical as well as the mechanistic discussions. In conclusion, the mainstream published work demonstrates the positive effects of vitamin B12 on semen quality: first, by increasing sperm count, and by enhancing sperm motility and reducing sperm DNA damage, though there are a few in vivo system studies that have deliberated some adverse effects. The beneficial effects of vitamin B12 on semen quality may be due to increased functionality of reproductive organs, decreased homocysteine toxicity, reduced amounts of generated nitric oxide, decreased levels of oxidative damage to sperm, reduced amount of energy produced by spermatozoa, decreased inflammation-induced semen impairment, and control of nuclear factor-κB activation. However, additional research, mainly clinical, is still needed to confirm these positive effects.

  16. Woodward's Synthesis of Vitamin B12

    Indian Academy of Sciences (India)

    consistently demonstrating the powerful use of logical reason- ing where it was customary to abandon such approaches. Barton further says, "We were taught to think that mechanism had nothing to do with 'real' Chemistry. With one lecture, Wood- ward showed us the contrary." Vitamin B12 is a large and complex molecule ...

  17. Binding-site analysis of opioid receptors using monoclonal anti-idiotypic antibodies

    International Nuclear Information System (INIS)

    Conroy, W.G.

    1988-01-01

    Structural relatedness between the variable region of anti-ligand antibodies and opioid binding sites allowed the generation of anti-idiotypic antibodies which recognized opioid receptors. The IgG 3 k antibodies which bound to opioid receptors were obtained when an anti-morphine antiserum was the idiotype. Both antibodies bound to opioid receptors, but only one of these blocked the binding of [ 3 H]naloxone. The antibody which did not inhibit the binding of [ 3 H]naloxone was itself displaced from the receptor by opioid ligands. The unique binding properties displayed by this antibody indicated that anti-idiotypic antibodies are not always a perfect image of the original ligand, and therefore may be more useful than typical ligands as probes for the receptor. An auto-anti-idiotypic technique was successfully used to obtain anti-opioid receptor antibodies. Another IgG 3 k antibody that blocked the binding of [ 3 H]naloxone to rat brain opioid receptors was obtained when a mouse was immunized with naloxone conjugated to bovine serum albumin. These data confirmed that an idiotype-anti-idiotype network which can generate an anti-receptor antibody normally functions when an opioid ligand is introduced into an animal in an immunogenic form

  18. [Folate, vitamin B12 and human health].

    Science.gov (United States)

    Brito, Alex; Hertrampf, Eva; Olivares, Manuel; Gaitán, Diego; Sánchez, Hugo; Allen, Lindsay H; Uauy, Ricardo

    2012-11-01

    During the past decade the role of folate and vitamin B12 in human nutrition have been under constant re-examination. Basic knowledge on the metabolism and interactions between these essential nutrients has expanded and multiple complexities have been unraveled. These micronutrients have shared functions and intertwined metabolic pathways that define the size of the "methyl donor" pool utilized in multiple metabolic pathways; these include DNA methylation and synthesis of nucleic acids. In Chile, folate deficiency is virtually nonexistent, while vitamin B12 deficiency affects approximately 8.5-51% depending on the cut-off value used to define deficiency. Folate is found naturally mainly in vegetables or added as folic acid to staple foods. Vitamin B12 in its natural form is present only in foods of animal origin, which is why deficit is more common among strict vegetarians and populations with a low intake of animal foods. Poor folate status in vulnerable women of childbearing age increases the risk of neural tube birth defects, so the critical time for the contribution of folic acid is several months before conception since neural tube closure occurs during the first weeks of life. The absorption of vitamin B12 from food is lower in older adults, who are considered to have higher risk of gastric mucosa atrophy, altered production of intrinsic factor and acid secretion. Deficiency of these vitamins is associated with hematological disorders. Vitamin B12 deficiency can also induce clinical and sub-clinical neurological and of other disorders. The purpose of this review is to provide an update on recent advances in the basic and applied knowledge of these vitamins relative to human health.

  19. Production of vitamin B12 and labeled vitamin B12 by Streptomyces griseus

    International Nuclear Information System (INIS)

    Mazaheri Tehrani, M.; Ghorbanzadeh Mashkani, S.; Tajer Mohammad Ghazvini, P.; Nazari, A.; Aflakee, F.

    2009-01-01

    In this study, the production of labeled vitamin B 12 with one strain of actinomycet in a novel synthetic medium by batch fermentation method was investigated. After releasing vitamin B 12 from microbial cells, the solution containing cobalamin analogues was fixed on amberlite XAD-4 exchanger and eluted by various solutions. Vitamin B 12 in the collected fractions were measured by HPLC method and also in order to confirm the existence of cobalamin compounds in the samples, TLC technique was used. In the optimal conditions, production of vitamin B 12 by this microorganism was 1456μg/1. The best recoveries of vitamin B 12 from the column were obtained when the column was eluted by ethanol followed by acetone. The R f , values for cyanocobalamin and methylcobalamin, produced by this microorganism were the same as the standard values of R f . The desorption of labeled vitamine B 12 was carried out by different eluants, including acetone, ethanol (absolute), ethanol 25% and deionized water. The activity of labeled vitamin B 12 was 8.55, 6.90, 0.79, 5.75 Bq/ml, respectively. Therefore, the total specific activity of 21.99 Bq/ml was obtained for labeled vitamin B 12 .

  20. Maximal load of the vitamin B12 transport system

    DEFF Research Database (Denmark)

    Lildballe, Dorte L; Mutti, Elena; Birn, Henrik

    2012-01-01

    Several studies suggest that the vitamin B12 (B12) transport system can be used for the cellular delivery of B12-conjugated drugs, also in long-term treatment Whether this strategy will affect the endogenous metabolism of B12 is not known. To study the effect of treatment with excess B12...

  1. Vitamin B12 and eicosanoids in insects

    International Nuclear Information System (INIS)

    Wakayama, J.E.

    1985-01-01

    Vitamin B 12 was not detected in the house fly, Musca domestica, which apparently cannot interconvert propionate and succinate. In contrast, the termite readily interconverts succinate and methylmalonate, and contains high amounts of vitamin B 12 . The intestinal bacteria were the major source of vitamin B 12 in the termite, Coptotermes formosanus. The presence of arachidonic acid (20:4) and eicosatrienoic acid (20:3,n-6) at low levels in adult male and female house flies was demonstrated by chemical ionization-gas chromatography-mass spectrometry. After injection, over 80% of 20:4 was rapidly incorporated into the phospholipid (PL) fraction. Over 80% of the sequestered 20:4 was in the 2-position of PLs. The 20:4 was injected into the insect or was included in the diet prior to administration of [ 3 H] 20:4; large amounts of radioactivity were recovered in the triacylglycerol and free fatty acid fractions. Arachidonic acid (20:4) injected into house flies was rapidly converted to prostaglandins, and was also catabolized rapidly. Radiolabeled 20:4 injected into the hemolymph was incorporated into the reproductive tissues of male insects. About 2.1% of the total radioactivity from [ 3 H] 20:4 injected into males just prior to mating was transferred to females during mating

  2. Site-Selective Orientated Immobilization of Antibodies and Conjugates for Immunodiagnostics Development

    Science.gov (United States)

    Rusling, James

    2016-01-01

    Immobilized antibody systems are the key to develop efficient diagnostics and separations tools. In the last decade, developments in the field of biomolecular engineering and crosslinker chemistry have greatly influenced the development of this field. With all these new approaches at our disposal, several new immobilization methods have been created to address the main challenges associated with immobilized antibodies. Few of these challenges that we have discussed in this review are mainly associated to the site-specific immobilization, appropriate orientation, and activity retention. We have discussed the effect of antibody immobilization approaches on the parameters on the performance of an immunoassay. PMID:27876681

  3. Inhibition of the vitamin B12 binding capacity of proteins by the hydrolysis product of cyclophosphamide

    International Nuclear Information System (INIS)

    Fenrych, W.; Ignatowicz, E.; Szczodrowska, E.

    1993-01-01

    The inhibitory effect of cyclophosphamide hydrolysis product (CPHP) on vitamin B 12 binding ability to proteins has been established. The ester N-(2-chloroethyl)-N'-(3-phosphopropyl)-etheylenediamine hydrochloride is probably responsible, in vitro, for blocking the protein binding sites. Preincubation of proteins with vitamin B 12 prevents the inhibitory effect of CPHP. (au)

  4. White centered retinal hemorrhages in vitamin b(12) deficiency anemia.

    Science.gov (United States)

    Zehetner, Claus; Bechrakis, Nikolaos E

    2011-05-01

    To report a case of severe vitamin B(12) deficiency anemia presenting with white centered retinal hemorrhages. Interventional case report. A 40-year-old man, general practitioner himself, presented with a 1-day history of diminished left visual acuity and a drop-shaped central scotoma. The corrected visual acuities were 20/20, OD and 20/100, OS. Ophthalmic examination revealed bilaterally pale tarsal conjunctiva, discretely icteric bulbar conjunctiva and disseminated white centered intraretinal hemorrhages with foveal involvement. OCT imaging through these lesions revealed a retinal thickening caused by a sub-ILM accumulation of hyperreflective and inhomogeneous deposits within the nerve fiber layer. Immediate laboratory work-up showed severe megaloblastic anemia caused by vitamin B(12) deficiency requiring erythrocyte transfusions. Most reports of white centered retinal hemorrhages have been described in patients with leukemic retinopathy and bacterial endocarditis. It is interesting that this case of vitamin B(12) deficiency anemia retinopathy has a clinically indistinguishable fundus appearance. This is probably due to the common pathology of capillary disruption and subsequent hemostatic fibrin plug formation. In megaloblastic anemia, direct anoxia results in endothelial dysfunction. The loss of impermeability allows extrusion of whole blood and subsequent diffusion from the disrupted site throughout and above the nerve fiber layer. Therefore the biomicroscopic pattern of white centered hemorrhages observed in anemic retinopathy is most likely due to the clot formation as the reparative sequence after capillary rupture.

  5. White Centered Retinal Hemorrhages in Vitamin B12 Deficiency Anemia

    Directory of Open Access Journals (Sweden)

    Claus Zehetner

    2011-05-01

    Full Text Available Background: To report a case of severe vitamin B12 deficiency anemia presenting with white centered retinal hemorrhages. Methods: Interventional case report. Results: A 40-year-old man, general practitioner himself, presented with a 1-day history of diminished left visual acuity and a drop-shaped central scotoma. The corrected visual acuities were 20/20, OD and 20/100, OS. Ophthalmic examination revealed bilaterally pale tarsal conjunctiva, discretely icteric bulbar conjunctiva and disseminated white centered intraretinal hemorrhages with foveal involvement. OCT imaging through these lesions revealed a retinal thickening caused by a sub-ILM accumulation of hyperreflective and inhomogeneous deposits within the nerve fiber layer. Immediate laboratory work-up showed severe megaloblastic anemia caused by vitamin B12 deficiency requiring erythrocyte transfusions. Discussion: Most reports of white centered retinal hemorrhages have been described in patients with leukemic retinopathy and bacterial endocarditis. It is interesting that this case of vitamin B12 deficiency anemia retinopathy has a clinically indistinguishable fundus appearance. This is probably due to the common pathology of capillary disruption and subsequent hemostatic fibrin plug formation. In megaloblastic anemia, direct anoxia results in endothelial dysfunction. The loss of impermeability allows extrusion of whole blood and subsequent diffusion from the disrupted site throughout and above the nerve fiber layer. Therefore the biomicroscopic pattern of white centered hemorrhages observed in anemic retinopathy is most likely due to the clot formation as the reparative sequence after capillary rupture.

  6. Avidity of anti-malarial antibodies inversely related to transmission intensity at three sites in Uganda.

    Science.gov (United States)

    Ssewanyana, Isaac; Arinaitwe, Emmanuel; Nankabirwa, Joaniter I; Yeka, Adoke; Sullivan, Richard; Kamya, Moses R; Rosenthal, Philip J; Dorsey, Grant; Mayanja-Kizza, Harriet; Drakeley, Chris; Greenhouse, Bryan; Tetteh, Kevin K A

    2017-02-10

    People living in malaria endemic areas acquire protection from severe malaria quickly, but protection from clinical disease and control of parasitaemia is acquired only after many years of repeated infections. Antibodies play a central role in protection from clinical disease; however, protective antibodies are slow to develop. This study sought to investigate the influence of Plasmodium falciparum exposure on the acquisition of high-avidity antibodies to P. falciparum antigens, which may be associated with protection. Cross-sectional surveys were performed in children and adults at three sites in Uganda with varied P. falciparum transmission intensity (entomological inoculation rates; 3.8, 26.6, and 125 infectious bites per person per year). Sandwich ELISA was used to measure antibody responses to two P. falciparum merozoite surface antigens: merozoite surface protein 1-19 (MSP1-19) and apical membrane antigen 1 (AMA1). In individuals with detectable antibody levels, guanidine hydrochloride (GuHCl) was added to measure the relative avidity of antibody responses by ELISA. Within a site, there were no significant differences in median antibody levels between the three age groups. Between sites, median antibody levels were generally higher in the higher transmission sites, with differences more apparent for AMA-1 and in ≥5 year group. Similarly, median avidity index (proportion of high avidity antibodies) showed no significant increase with increasing age but was significantly lower at sites of higher transmission amongst participants ≥5 years of age. Using 5 M GuHCl, the median avidity indices in the ≥5 year group at the highest and lowest transmission sites were 19.9 and 26.8, respectively (p = 0.0002) for MSP1-19 and 12.2 and 17.2 (p = 0.0007) for AMA1. Avidity to two different P. falciparum antigens was lower in areas of high transmission intensity compared to areas with lower transmission. Appreciation of the mechanisms behind these findings as

  7. 21 CFR 862.1810 - Vitamin B12 test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Vitamin B12 test system. 862.1810 Section 862.1810....1810 Vitamin B12 test system. (a) Identification. A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in the...

  8. New method for the radioactive determination of vitamin B12

    International Nuclear Information System (INIS)

    Lewin, Nathan; Fries, J.E.; Richards, C.S.

    1975-01-01

    A description is given of a method for the radioactive determination of vitamin B12 in a sample solution of serum in which a radioactive tracer of vitamin B12 and the vitamin B12 of the serum compete with respect to an intrinsic factor of limited linking capacity. The free radioactive vitamin B12 and the free vitamin B12 of the serum are separated from the intrinsic factor and from the radioactive vitamin B12 and from the serum vitamin B12 linked to this factor, before the radioactivity is measured against standard values. The method consists in separating the free radioactive vitamin B12 and the free serum vitamin B12 of the intrinsic factor and portions of radioactive and serum vitamin B12 linked to this factor, by adding an adequate quantity of bentonite to adsorb the free radioactive vitamin B12 and free serum vitamin B12 so that the intrinsic factor surface floating solution in association with the linked radioactive vitamin B12 and the linked serum vitamin B12 may be physically isolated from the solid bentonite that has adsorbed the free radioactive vitamin B12 and the free serum vitamin B12 [fr

  9. Human antibody recognition of antigenic site IV on Pneumovirus fusion proteins.

    Science.gov (United States)

    Mousa, Jarrod J; Binshtein, Elad; Human, Stacey; Fong, Rachel H; Alvarado, Gabriela; Doranz, Benjamin J; Moore, Martin L; Ohi, Melanie D; Crowe, James E

    2018-02-01

    Respiratory syncytial virus (RSV) is a major human pathogen that infects the majority of children by two years of age. The RSV fusion (F) protein is a primary target of human antibodies, and it has several antigenic regions capable of inducing neutralizing antibodies. Antigenic site IV is preserved in both the pre-fusion and post-fusion conformations of RSV F. Antibodies to antigenic site IV have been described that bind and neutralize both RSV and human metapneumovirus (hMPV). To explore the diversity of binding modes at antigenic site IV, we generated a panel of four new human monoclonal antibodies (mAbs) and competition-binding suggested the mAbs bind at antigenic site IV. Mutagenesis experiments revealed that binding and neutralization of two mAbs (3M3 and 6F18) depended on arginine (R) residue R429. We discovered two R429-independent mAbs (17E10 and 2N6) at this site that neutralized an RSV R429A mutant strain, and one of these mAbs (17E10) neutralized both RSV and hMPV. To determine the mechanism of cross-reactivity, we performed competition-binding, recombinant protein mutagenesis, peptide binding, and electron microscopy experiments. It was determined that the human cross-reactive mAb 17E10 binds to RSV F with a binding pose similar to 101F, which may be indicative of cross-reactivity with hMPV F. The data presented provide new concepts in RSV immune recognition and vaccine design, as we describe the novel idea that binding pose may influence mAb cross-reactivity between RSV and hMPV. Characterization of the site IV epitope bound by human antibodies may inform the design of a pan-Pneumovirus vaccine.

  10. Site-specific proteolytic degradation of IgG monoclonal antibodies expressed in tobacco plants.

    Science.gov (United States)

    Hehle, Verena K; Lombardi, Raffaele; van Dolleweerd, Craig J; Paul, Mathew J; Di Micco, Patrizio; Morea, Veronica; Benvenuto, Eugenio; Donini, Marcello; Ma, Julian K-C

    2015-02-01

    Plants are promising hosts for the production of monoclonal antibodies (mAbs). However, proteolytic degradation of antibodies produced both in stable transgenic plants and using transient expression systems is still a major issue for efficient high-yield recombinant protein accumulation. In this work, we have performed a detailed study of the degradation profiles of two human IgG1 mAbs produced in plants: an anti-HIV mAb 2G12 and a tumour-targeting mAb H10. Even though they use different light chains (κ and λ, respectively), the fragmentation pattern of both antibodies was similar. The majority of Ig fragments result from proteolytic degradation, but there are only a limited number of plant proteolytic cleavage events in the immunoglobulin light and heavy chains. All of the cleavage sites identified were in the proximity of interdomain regions and occurred at each interdomain site, with the exception of the VL /CL interface in mAb H10 λ light chain. Cleavage site sequences were analysed, and residue patterns characteristic of proteolytic enzymes substrates were identified. The results of this work help to define common degradation events in plant-produced mAbs and raise the possibility of predicting antibody degradation patterns 'a priori' and designing novel stabilization strategies by site-specific mutagenesis. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  11. Detection of vitamin B12 deficiency in older people by measuring vitamin B12 or the active fraction of vitamin B12, holotranscobalamin

    DEFF Research Database (Denmark)

    Clarke, Robert; Sherliker, Paul; Hin, Harold

    2007-01-01

    BACKGROUND: Impaired vitamin B(12) function and decreased vitamin B(12) status have been associated with neurological and cognitive impairment. Current assays analyze total vitamin B(12) concentration, only a small percentage of which is metabolically active. Concentrations of this active component......, carried on holotranscobalamin (holoTC), may be of greater relevance than total vitamin B(12). METHODS: We compared the utility of serum holoTC with conventional vitamin B(12) for detection of vitamin B(12) deficiency in a population-based study of older people, using increased methylmalonic acid (MMA......) concentrations as a marker of metabolic vitamin B(12) deficiency in the overall population (n = 2403) and in subsets with normal (n = 1651) and abnormal (n = 752) renal function. RESULTS: Among all participants, 6% had definite (MMA >0.75 micromol/L) and 16% had probable (MMA >0.45 micromol/L) metabolic vitamin...

  12. Localized conformational interrogation of antibody and antibody-drug conjugates by site-specific carboxyl group footprinting.

    Science.gov (United States)

    Pan, Lucy Yan; Salas-Solano, Oscar; Valliere-Douglass, John F

    Establishing and maintaining conformational integrity of monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) during development and manufacturing is critical for ensuring their clinical efficacy. As presented here, we applied site-specific carboxyl group footprinting (CGF) for localized conformational interrogation of mAbs. The approach relies on covalent labeling that introduces glycine ethyl ester tags onto solvent-accessible side chains of protein carboxylates. Peptide mapping is used to monitor the labeling kinetics of carboxyl residues and the labeling kinetics reflects the conformation or solvent-accessibility of side chains. Our results for two case studies are shown here. The first study was aimed at defining the conformational changes of mAbs induced by deglycosylation. We found that two residues in C H 2 domain (D268 and E297) show significantly enhanced side chain accessibility upon deglycosylation. This site-specific result highlighted the advantage of monitoring the labeling kinetics at the amino acid level as opposed to the peptide level, which would result in averaging out of highly localized conformational differences. The second study was designed to assess conformational effects brought on by conjugation of mAbs with drug-linkers. All 59 monitored carboxyl residues displayed similar solvent-accessibility between the ADC and mAb under native conditions, which suggests the ADC and mAb share similar side chain conformation. The findings are well correlated and complementary with results from other assays. This work illustrated that site-specific CGF is capable of pinpointing local conformational changes in mAbs or ADCs that might arise during development and manufacturing. The methodology can be readily implemented within the industry to provide comprehensive conformational assessment of these molecules.

  13. Two-site sandwich radioimmunoassay of human gamma interferon with monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, E; Imai, M; Usuda, S; Tachibana, K; Okamoto, H; Ohike, Y; Nakamura, T; Miyakawa, Y; Mayumi, M [Jichi Medical School, Minamikawachi, Tochigi (Japan)

    1985-03-18

    Two monoclonal antibodies were raised against human gamma interferon (IFN-..gamma..) derived from E. coli harboring the recombinant cDNA for IFN-..gamma.., and one against a synthetic peptide representing its C-terminus amino acid sequence of 20 residues. The monoclonal antibody against the synthetic peptide reacted either with IFN-..gamma.. or the synthetic peptide. One monoclonal anti-IFN-..gamma.. did not react with the synthetic peptide, while the other showed a weak binding with the peptide. A 2-site '1-step' radioimmunoassay was developed. The assay was rapid with a sensitivity capable of detecting a few ng/ml of IFN-..gamma...

  14. Radiolysis of cyanocobalamin (vitamin B12)

    International Nuclear Information System (INIS)

    Juanchi, X.; Albarran, G.; Negron-Mendoza, A.

    2000-01-01

    Research on the radiolysis of vitamins is of considerable interest since these compounds are important nutritional constituents in foods and in dietetic supplements. In spite of these considerations there are few data and very often difficult to compare for the radiolytic behavior of vitamins. In this work we focused our attention on to the study of the radiolysis of cyanocobalamin (vitamin B 12 ) in solid state and in aqueous solutions. The procedure was followed by HPLC and UV-spectroscopy. The results obtained in aqueous solutions showed a dependence of the decomposition as a linear function of the dose. The G of decomposition for a 1x10 -5 M solution was 3.3. In the solid state the vitamin was very stable towards the irradiation in the conditions used in this study with a G=2.1x10 -3 . A study made with Serratia marcescens as a microbiological contaminant showed that at the sterilization dose there is a destruction of the vitamin in aqueous solution. In the solid state the degree of decomposition was 7%. (author)

  15. Fusion proteins of HIV-1 envelope glycoprotein gp120 with CD4-induced antibodies showed enhanced binding to CD4 and CD4 binding site antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Weizao, E-mail: chenw3@mail.nih.gov [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Feng, Yang [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Wang, Yanping [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); The Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Zhu, Zhongyu; Dimitrov, Dimiter S. [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Some recombinant HIV-1 gp120s do not preserve their conformations on gp140s. Black-Right-Pointing-Pointer We hypothesize that CD4i antibodies could induce conformational changes in gp120. Black-Right-Pointing-Pointer CD4i antibodies enhance binding of CD4 and CD4bs antibodies to gp120. Black-Right-Pointing-Pointer CD4i antibody-gp120 fusion proteins could have potential as vaccine immunogens. -- Abstract: Development of successful AIDS vaccine immunogens continues to be a major challenge. One of the mechanisms by which HIV-1 evades antibody-mediated neutralizing responses is the remarkable conformational flexibility of its envelope glycoprotein (Env) gp120. Some recombinant gp120s do not preserve their conformations on gp140s and functional viral spikes, and exhibit decreased recognition by CD4 and neutralizing antibodies. CD4 binding induces conformational changes in gp120 leading to exposure of the coreceptor-binding site (CoRbs). In this study, we test our hypothesis that CD4-induced (CD4i) antibodies, which target the CoRbs, could also induce conformational changes in gp120 leading to better exposed conserved neutralizing antibody epitopes including the CD4-binding site (CD4bs). We found that a mixture of CD4i antibodies with gp120 only weakly enhanced CD4 binding. However, such interactions in single-chain fusion proteins resulted in gp120 conformations which bound to CD4 and CD4bs antibodies better than the original or mutagenically stabilized gp120s. Moreover, the two molecules in the fusion proteins synergized with each other in neutralizing HIV-1. Therefore, fusion proteins of gp120 with CD4i antibodies could have potential as components of HIV-1 vaccines and inhibitors of HIV-1 entry, and could be used as reagents to explore the conformational flexibility of gp120 and mechanisms of entry and immune evasion.

  16. Vitamin B12 Deficiency in Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Carlos Tavares Bello

    2017-10-01

    Conclusion: Further studies are needed to identify the risk factors for the B12 deficit. The recognition of these variables will contribute to optimize the screening and prevention of the B12 deficiency in type 2 diabetes mellitus.

  17. 21 CFR 184.1945 - Vitamin B12.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Vitamin B12. 184.1945 Section 184.1945 Food and... Substances Affirmed as GRAS § 184.1945 Vitamin B12. (a) Vitamin B12, also known as cyanocobalamin (C63H88Co... is used in food at levels not to exceed current good manufacturing practice. Vitamin B12 also may be...

  18. Simultaneous radioassay of folate and vitamin B12

    International Nuclear Information System (INIS)

    1981-01-01

    An improved simultaneous radioassay for folate and vitamin B 12 in biological specimens is described. A sample containing folate and vitamin B 12 is contacted with 125 I-folate and 57 Co-vitamin B 12 and their respective specific binders. After separation of the bound and free portions, the radioactivity in the portions is counted and the amounts of folate and vitamin B 12 then determined from standard curves. (U.K.)

  19. Degradation of vitamin B12 in dietary supplements.

    Science.gov (United States)

    Yamada, Keiko; Shimodaira, Michiko; Chida, Seiko; Yamada, Noriko; Matsushima, Norio; Fukuda, Morimichi; Yamada, Shoji

    2008-01-01

    Beverages and solid dietary supplements rich in various added vitamins and minerals have recently become available. It seems reasonable to consider that the intake of these foods is convenient for easy ingestion of nutrients, but problems caused by blending different nutrients in high concentrations have arisen. We focused on vitamin B12 (B12) among vitamins and determined the B12 contents of beverages and solid dietary supplements purchased from a retail shop. The B12 contents of three of five beverages were less than stated on the labels. On the other hand, certain beverages unexpectedly contained much more B12 than stated on the labels. In these beverages the amount of B12 decreased rapidly with time, whereas B12 content was lower than stated on the label in only one of four solid dietary supplements. The content of B12 was affected by storage time, light exposure, temperature and vitamin C. From experimental analysis with a competitive binding assay method employing a ACS Chemiluminescent B12 kit, examining differential binding by intrinsic factors and spectral analysis of B12, it was determined that some of the B12 might have been converted into B12 analogues or small degradation products by multinutrient interaction during storage.

  20. 21 CFR 582.5945 - Vitamin B12.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Vitamin B12. 582.5945 Section 582.5945 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5945 Vitamin B12. (a) Product. Vitamin B12. (b) Conditions of use. This substance is...

  1. Production Of Vitamin B 12 By Streptomyces Fulvissimus | Atta ...

    African Journals Online (AJOL)

    Fifty five of actinomycete isolates were screened for vitamin B12 production by growing on soybean meal medium fortified with cobalt. Only one AZ-Z-88 among nine actinomycete cultures was found to produce significantly higher yield of the vitamin B12 (64.57 ug/ml). Determination of vitamin B12 production was carried out ...

  2. Site-specific photoconjugation of antibodies using chemically synthesized IgG-binding domains.

    Science.gov (United States)

    Perols, Anna; Karlström, Amelie Eriksson

    2014-03-19

    Site-specific labeling of antibodies can be performed using the immunoglobulin-binding Z domain, derived from staphylococcal protein A (SpA), which has a well-characterized binding site in the Fc region of antibodies. By introducing a photoactivable probe in the Z domain, a covalent bond can be formed between the Z domain and the antibody by irradiation with UV light. The aim of this study was to improve the conjugation yield for labeling of different subclasses of IgG having different sequence composition, using a photoactivated Z domain variant. Four different variants of the Z domain (Z5BPA, Z5BBA, Z32BPA, and Z32BBA) were synthesized to investigate the influence of the position of the photoactivable probe and the presence of a flexible linker between the probe and the protein. For two of the variants, the photoreactive benzophenone group was introduced as part of an amino acid side chain by incorporation of the unnatural amino acid benzoylphenylalanine (BPA) during peptide synthesis. For the other two variants, the photoreactive benzophenone group was attached via a flexible linker by coupling of benzoylbenzoic acid (BBA) to the ε-amino group of a selectively deprotected lysine residue. Photoconjugation experiments using human IgG1, mouse IgG1, and mouse IgG2A demonstrated efficient conjugation for all antibodies. It was shown that differences in linker length had a large impact on the conjugation efficiency for labeling of mouse IgG1, whereas the positioning of the photoactivable probe in the sequence of the protein had a larger effect for mouse IgG2A. Conjugation to human IgG1 was only to a minor extent affected by position or linker length. For each subclass of antibody, the best variant tested using a standard conjugation protocol resulted in conjugation efficiencies of 41-66%, which corresponds to on average approximately one Z domain attached to each antibody. As a combination of the two best performing variants, Z5BBA and Z32BPA, a Z domain variant with

  3. Maturation Pathways of Cross-Reactive HIV-1 Neutralizing Antibodies

    Directory of Open Access Journals (Sweden)

    Dimiter S. Dimitrov

    2009-11-01

    Full Text Available Several human monoclonal antibodies (hmAbs and antibody fragments, including the best characterized in terms of structure-function b12 and Fab X5, exhibit relatively potent and broad HIV-1 neutralizing activity. However, the elicitation of b12 or b12-like antibodies in vivo by vaccine immunogens based on the HIV-1 envelope glycoprotein (Env has not been successful. B12 is highly divergent from the closest corresponding germline antibody while X5 is less divergent. We have hypothesized that the relatively high degree of specific somatic hypermutations may preclude binding of the HIV-1 envelope glycoprotein (Env to closest germline antibodies, and that identifying antibodies that are intermediates in the pathways to maturation could help design novel vaccine immunogens to guide the immune system for their enhanced elicitation. In support of this hypothesis we have previously found that a germline-like b12 (monovalent and bivalent scFv as an Fc fusion protein or IgG lacks measurable binding to an Env as measured by ELISA with a sensitivity in the μM range [1]; here we present evidence confirming and expanding these findings for a panel of Envs. In contrast, a germline-like scFv X5 bound Env with high (nM affinity. To begin to explore the maturation pathways of these antibodies we identified several possible b12 intermediate antibodies and tested their neutralizing activity. These intermediate antibodies neutralized only some HIV-1 isolates and with relatively weak potency. In contrast, germline-like scFv X5 neutralized a subset of the tested HIV-1 isolates with comparable efficiencies to that of the mature X5. These results could help explain the relatively high immunogenicity of the coreceptor binding site on gp120 and the abundance of CD4-induced (CD4i antibodies in HIV-1-infected patients (X5 is a CD4i antibody as well as the maturation pathway of X5. They also can help identify antigens that can bind specifically to b12 germline and

  4. Simultaneous radioassay of folate and vitamin B12

    International Nuclear Information System (INIS)

    Gutcho, S.; Mansbach, L.

    1979-01-01

    A serum sample is heated at an alkaline pH to release folate and vitamin B 12 from endogenous binders. A simultaneous radioassay for folate and vitamin B 12 is effected by contacting the sample with binder for folate, binder for vitamin B 12 , folote labeled with one radioactive isotope and vitamin B 12 labeled with another radioacitve isotope, followed by separation of bound and free portions, and determination of the radioactivity of at least one of the portions. The amounts of folate and vitamin B 12 present in the sample may be determined from standard curves

  5. Vitamin B12 assays compared by use of patients sera with low vitamin B12 content

    International Nuclear Information System (INIS)

    Sheridan, B.L.; Pearce, L.C.

    1985-01-01

    The authors compared four radioisotope dilution (RD) methods and a microbiological assay for measuring concentrations of vitamin B12 in a selected panel of serum samples from patients known to be deficient in the vitamin. Low (less than 100 ng/L) and borderline (100-180 ng/L) results were similar between methods, but use of the manufacturers recommended ranges for borderline results would have changed the diagnostic classifications for 22 of 38 samples. Results of all the RD methods inter-correlated well, but less so with the microbiological assay. Borderline, nondiagnostic results were common to all methods, and no apparent advantage was gained from using the microbiological assay

  6. Vitamin B12 Deficiency in Relation to Functional Disabilities

    Directory of Open Access Journals (Sweden)

    Heather E. Rasmussen

    2013-11-01

    Full Text Available This study was designed to assess whether symptoms, functional measures, and reported disabilities were associated with vitamin B12 (B12 deficiency when defined in three ways. Participants, aged 60 or more years of age, in 1999–2002 National Health and Nutrition Examination Surveys (NHANES were categorized in relation to three previously used definitions of B12 deficiency: (1 serum B12 20 μmol/L; and (3 serum B12 0.21 μmol/L. Functional measures of peripheral neuropathy, balance, cognitive function, gait speed, along with self-reported disability (including activities of daily living were examined with standardized instruments by trained NHANES interviewers and technicians. Individuals identified as B12 deficient by definition 2 were more likely to manifest peripheral neuropathy OR (odds (95% confidence intervals, p value: 9.70 (2.24, 42.07, 0.004 and report greater total disability, 19.61 (6.22, 61.86 0.0001 after adjustments for age, sex, race, serum creatinine, and ferritin concentrations, smoking, diabetes, and peripheral artery disease. Smaller, but significantly increased, odds of peripheral neuropathy and total disability were also observed when definition 3 was applied. Functional measures and reported disabilities were associated with B12 deficiency definitions that include B12 biomarkers (homocysteine or methylmalonic acid. Further study of these definitions is needed to alert clinicians of possible subclinical B12 deficiency because functional decline amongst older adults may be correctable if the individual is B12 replete.

  7. The effects of variations in the specificities of the antibody components on a two-site immunoradiometric assay for ferritin

    International Nuclear Information System (INIS)

    Cowan, S.I.; Stagg, B.H.; Niemann, E.

    1977-01-01

    Variations in the sub-unit antigenic structure of ferritins derived from various human tissues are reflected in the differing specificities of antisera raised against these ferritin preparations. In this study it was shown that antibody specificity played an important role in determining the sensitivity and overall binding of labelled antibody in a two-site immunoradiometric assay for ferritin. Homologous assay systems, in which solid phase and radiolabelled antibodies were of similar specificities, were generally less sensitive and showed lower binding than heterologous assay systems, in which solid phase and labelled antibodies were of different specificities. The source of the ferritin which was used as assay standard also played an important part in determining the sensitivity and overall binding in homologous antibody systems, spleen ferritin standards yielding assays superior to those obtained with placenta or liver ferritin standards. However, these differences between standards were not seen in a heterologous system employing solid phase antibodies directed against liver ferritin and labelled antibodies directed against placenta ferritin. The nature of the ferritin used to prepare immunoadsorbant for the purification of antibodies prior to radioiodination also affected the assay characteristics; antibodies prepared on spleen ferritin immunoadsorbant being more reactive than antibodies prepared on placenta ferritin immunoadsorbant, which in turn were more reactive then antibodies prepared on liver ferritin immunoadsorbant. (orig.) [de

  8. Synthesis of site-heterologous haptens for high-affinity anti-pyraclostrobin antibody generation.

    Science.gov (United States)

    Mercader, Josep V; Agulló, Consuelo; Abad-Somovilla, Antonio; Abad-Fuentes, Antonio

    2011-03-07

    The design and synthesis of functional chemical derivatives of small organic molecules is usually a key step for the intricate production of a variety of bioconjugates. In this respect, the derivatization site at which the spacer arm is introduced in immunizing conjugates constitutes a highly critical parameter for the generation of high-affinity and selective antibodies. However, due to the usual complexity of the required synthetic procedures, the appropriate comparison of alternative tethering positions has often been neglected. In the present study, meticulous strategies were followed to prepare synthetic derivatives of pyraclostrobin with the same linkers located at diverse rationally-chosen sites. Activity appraisal of antibodies and bioconjugates was carried out by bidimensional competitive direct and indirect immunoassays, and a superior performance of two of the three synthesized haptens was found. Finally, a detailed analysis of the conformations of the target molecule and the synthesized haptens in aqueous solution was done using computer assisted molecular modeling techniques. This study suggested that the lower titers and affinities of one set of antibodies are most probably due to conformational effects of the spacer arm in the immunizing bioconjugate.

  9. Vitamin B12-Containing Plant Food Sources for Vegetarians

    Science.gov (United States)

    Watanabe, Fumio; Yabuta, Yukinori; Bito, Tomohiro; Teng, Fei

    2014-01-01

    The usual dietary sources of Vitamin B12 are animal-derived foods, although a few plant-based foods contain substantial amounts of Vitamin B12. To prevent Vitamin B12 deficiency in high-risk populations such as vegetarians, it is necessary to identify plant-derived foods that contain high levels of Vitamin B12. A survey of naturally occurring plant-derived food sources with high Vitamin B12 contents suggested that dried purple laver (nori) is the most suitable Vitamin B12 source presently available for vegetarians. Furthermore, dried purple laver also contains high levels of other nutrients that are lacking in vegetarian diets, such as iron and n-3 polyunsaturated fatty acids. Dried purple laver is a natural plant product and it is suitable for most people in various vegetarian groups. PMID:24803097

  10. Vitamin B12-Containing Plant Food Sources for Vegetarians

    Directory of Open Access Journals (Sweden)

    Fumio Watanabe

    2014-05-01

    Full Text Available The usual dietary sources of Vitamin B12 are animal-derived foods, although a few plant-based foods contain substantial amounts of Vitamin B12. To prevent Vitamin B12 deficiency in high-risk populations such as vegetarians, it is necessary to identify plant-derived foods that contain high levels of Vitamin B12. A survey of naturally occurring plant-derived food sources with high Vitamin B12 contents suggested that dried purple laver (nori is the most suitable Vitamin B12 source presently available for vegetarians. Furthermore, dried purple laver also contains high levels of other nutrients that are lacking in vegetarian diets, such as iron and n-3 polyunsaturated fatty acids. Dried purple laver is a natural plant product and it is suitable for most people in various vegetarian groups.

  11. Lhermitte's sign and vitamin B12 deficiency: case report

    OpenAIRE

    Teive, Hélio Afonso Ghizoni; Haratz, Salo; Zavala, Jorge; Munhoz, Renato Puppi; Scola, Rosana Hermínia; Werneck, Lineu César

    2009-01-01

    CONTEXT AND OBJECTIVE: Lhermitte's sign, a classical neurological sign, is a rare manifestation of vitamin B12 deficiency. The aim here was to report on a case of an elderly patient with vitamin B12 deficiency whose first clinical manifestation was the presence of Lhermitte's sign. CASE REPORT: We describe an elderly patient with vitamin B12 deficiency who presented cognitive dysfunction, peripheral polyneuropathy and sensory ataxia, and whose first clinical manifestation was the presence of ...

  12. Racial difference in serum Vitamin B12 levels

    International Nuclear Information System (INIS)

    Kwee, H.G.; Bowman, H.S.; Wells, L.W.

    1985-01-01

    Measurements of the serum Vitamin B 12 concentrations of 49 black and 49 white healthy adults demonstrate a significantly higher mean serum Vitamin B 12 level in blacks when compared to whites. The reason for this difference appears to be genetic, although environmental factors may also be involved. It is suggested that clinical laboratories should establish their own separate reference values of serum Vitamin B 12 for blacks and whites in order to prevent misinterpretation of test results

  13. Prevalence of Vitamin B12 and Folate Deficiencies and ...

    African Journals Online (AJOL)

    ... 2Faculty of Dentistry, International Branch, 3Department of Internal Medicine & Endocrine and ... Keywords: Vitamin B12 deficiency, Folate deficiency, Homocysteinemia, Elderly population ... gastritis, intestinal malabsorption, pancreatic.

  14. Folic acid fortification: why not vitamin B12 also?

    Science.gov (United States)

    Selhub, Jacob; Paul, Ligi

    2011-01-01

    Folic acid fortification of cereal grains was introduced in many countries to prevent neural tube defect occurrence. The metabolism of folic acid and vitamin B12 intersect during the transfer of the methyl group from 5-methyltetrahydrofolate to homocysteine catalyzed by B12-dependent methioine synthase. Regeneration of tetrahydrofolate via this reaction makes it available for synthesis of nucleotide precursors. Thus either folate or vitamin B12 deficiency can result in impaired cell division and anemia. Exposure to extra folic acid through fortification may be detrimental to those with vitamin B12 deficiency. Among participants of National Health And Nutrition Examination Survey with low vitamin B12 status, high serum folate (>59 nmol/L) was associated with higher prevalence of anemia and cognitive impairment when compared with normal serum folate. We also observed an increase in the plasma concentrations of total homocysteine and methylmalonic acid (MMA), two functional indicators of vitamin B12 status, with increase in plasma folate under low vitamin B12 status. These data strongly imply that high plasma folate is associated with the exacerbation of both the biochemical and clinical status of vitamin B12 deficiency. Hence any food fortification policy that includes folic acid should also include vitamin B12. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

  15. Three-site sandwich radioimmunoassay with monoclonal antibodies for a sensitive determination of human alpha-fetoprotein

    International Nuclear Information System (INIS)

    Nomura, M.; Imai, M.; Takahashi, K.; Kumakura, T.; Tachibana, K.; Aoyagi, S.; Usuda, S.; Nakamura, T.; Miyakawa, Y.; Mayumi, M.

    1983-01-01

    Utilizing monoclonal antibodies against human alpha-fetoprotein, 3 distinct antigenic determinants were identified. These antigenic determinants, provisionally designated a, b and c, were arranged in such a manner that the binding of one determinant with the corresponding antibody did not inhibit, or only barely inhibited the binding of antibodies directed to the other 2 determinants. Monoclonal antibodies with 3 different specificities were, therefore, applied to develop a sandwich-type solid-phase radioimmunoassay of the antigen in which wells were coated with anti-a, and radiolabeled anti-b together with radiolabeled anti-c was employed to detect the bound antigen. The 3-site sandwich radioimmunoassay involving 3 different determinants gave a higher sensitivity than 2-site assays in which only anti-b or anti-c was employed as a radiolabeled reagent, because the radioactivity of the 2 labeled antibodies was added on the antigen bound to immobilized anti-a. (Auth.)

  16. Electron addition to alkyl cobalamins, coenzyme B12 and vitamin B12

    International Nuclear Information System (INIS)

    Rao, D.N.R.; Symons, M.C.R.

    1983-01-01

    Exposure of dilute solutions of methyl and ethyl cobalamins and coenzyme B 12 in dilute solutions (D 2 O+CD 3 OD) to 60 Co #betta#-rays at 77 K gave a single broad feature in the free-spin region assigned to electron-capture species with the excess electron largely confined to a π* corrin orbital. On warming above 77 K the methyl derivative gave a novel species with spectral features characteristic of an unpaired electron in the Co(dsub(x 2 -y 2 )) orbital. The other two substrates gave spectra due to Cosup(II)Bsub(12r) both on warming and after photolyses with visible light. The acetyl derivative gave an electron-capture species whose e.s.r. spectrum was characteristic of an electron in the Co(dsub(z 2 )) orbital, which on warming above 77 K changed to the normal Cosup(II)Bsub(12r) spectrum. The cyano derivative (vitamin B 12 ) gave electron addition into the Co(dsub(z 2 )) orbital, as evidenced by the large hyperfine coupling to 13 C from 13 CN ligands. On annealing, cyanide ions were lost irreversibly, Bsub(12r) being detected by e.s.r. spectroscopy. In contrast, the dicyano derivative on electron addition at 77 K gave a species containing only one 13 CN ligand. Hence in this case one CN - ligand was lost at 77 K, with no return of the dimethylbenzimidazole ligand. These results are discussed in terms of a new mechanism for electron-addition to alkyl cobalamins. (author)

  17. Immunological Reactivity Using Monoclonal and Polyclonal Antibodies of Autoimmune Thyroid Target Sites with Dietary Proteins

    Directory of Open Access Journals (Sweden)

    Datis Kharrazian

    2017-01-01

    Full Text Available Many hypothyroid and autoimmune thyroid patients experience reactions with specific foods. Additionally, food interactions may play a role in a subset of individuals who have difficulty finding a suitable thyroid hormone dosage. Our study was designed to investigate the potential role of dietary protein immune reactivity with thyroid hormones and thyroid axis target sites. We identified immune reactivity between dietary proteins and target sites on the thyroid axis that includes thyroid hormones, thyroid receptors, enzymes, and transport proteins. We also measured immune reactivity of either target specific monoclonal or polyclonal antibodies for thyroid-stimulating hormone (TSH receptor, 5′deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin, thyroxine, and triiodothyronine against 204 purified dietary proteins commonly consumed in cooked and raw forms. Dietary protein determinants included unmodified (raw and modified (cooked and roasted foods, herbs, spices, food gums, brewed beverages, and additives. There were no dietary protein immune reactions with TSH receptor, thyroid peroxidase, and thyroxine-binding globulin. However, specific antigen-antibody immune reactivity was identified with several purified food proteins with triiodothyronine, thyroxine, thyroglobulin, and 5′deiodinase. Laboratory analysis of immunological cross-reactivity between thyroid target sites and dietary proteins is the initial step necessary in determining whether dietary proteins may play a potential immunoreactive role in autoimmune thyroid disease.

  18. Holo-transcobalamin is an indicator of vitamin B-12 absorption in healthy adults with adequate vitamin B-12 status

    DEFF Research Database (Denmark)

    von Castel-Roberts, Kristina M; Mørkbak, Anne Louise; Nexo, Ebba

    2007-01-01

    BACKGROUND: It has been hypothesized that the response of holo-transcobalamin (holo-TC) to oral vitamin B-12 may be used to assess absorption. To develop a reliable clinical absorption test that uses holo-TC, it is necessary to determine the optimal timeline for vitamin B-12 administration...... and postdose assessment. OBJECTIVE: The objective of this study was to assess the magnitude and patterns of change in the postabsorption response of holo-TC to oral vitamin B-12. DESIGN: Adult (18-49 y) male and female participants (n = 21) with normal vitamin B-12 status were given three 9-mug doses...... of vitamin B-12 at 6-h intervals beginning early morning (baseline) on day 1. Blood was drawn at 17 timed intervals over the course of 3 d for the analysis of holo-TC and other indicators of vitamin B-12 status. RESULTS: Mean holo-TC increased significantly (P

  19. ETAC reagents: A new class of sulfhydryl site-specific radiolabelling probes for antibodies

    International Nuclear Information System (INIS)

    del Rosario, R.B.; Brocchini, S.J.; Baron, L.A.; Smith, R.H.; Lawton, R.G.; Wahl, R.L.

    1990-01-01

    A new class of bis-alkylating Michael reagents, equilibrium transfer crosslink reagents, 'ETAC', which combine the techniques of crosslinking with tethering have been synthesized. Following a succession of Michael and retro-Michael additions and elimination of the arylsulfone groups, reduced heavy-heavy and heavy-light disulfide links of an anti-ovarian IgG2a monoclonal antibody, 5G6.4, were site-specifically re-annealed via a 3-carbon bridge having a tether branch containing a designated label

  20. Gastric emptying in patients with vitamin B12 deficiency

    International Nuclear Information System (INIS)

    Yagci, Muenci; Yamac, Kadri; Acar, Kadir; Haznedar, Rauf; Cingi, Elif; Kitapci, Mehmet

    2002-01-01

    The clinical presentation of patients with vitamin B 12 deficiency varies in a spectrum ranging from haematological disorders to neuropsychiatric diseases. In rare cases, orthostatic hypotension, impotence, constipation and urinary retention have been attributed to autonomic nervous system dysfunction due to vitamin B 12 deficiency. The aim of this study was to evaluate the effect of vitamin B 12 deficiency on autonomic nervous system function by studying gastric emptying times (T 1/2 ). Twenty patients with newly diagnosed vitamin B 12 deficiency and 12 control patients with gastritis and normal vitamin B 12 levels were enrolled in this study. Gastroduodenoscopy, endoscopic biopsy, histopathological evaluation of the biopsy specimens and radionuclide gastric emptying studies were performed. After vitamin B 12 replacement therapy for 3 months, radionuclide gastric emptying studies were repeated. Mean gastric emptying T 1/2 in patients before and after treatment and in controls were 103.83±48.80 min, 90.00±17.29 min and 74.55±8.52 min, respectively. The difference in mean gastric emptying T 1/2 between patients before treatment and controls was statistically significant (P 12 treatment (P 1/2 was somewhat shorter. There were no positive or negative correlations between gastric emptying T 1/2 and the following parameters: haemoglobin, vitamin B 12 level and Helicobacter pylori positivity. In conclusion, gastric emptying T 1/2 was prolonged in patients with vitamin B 12 deficiency and this prolongation was not corrected after vitamin B 12 replacement therapy. Although autonomic nervous system dysfunction due to vitamin B 12 deficiency rarely gives rise to clinical manifestations, latent dysfunction demonstrated by laboratory tests seems to be a frequent phenomenon. The level of vitamin B 12 does not correlate with the degree of autonomic nervous system dysfunction measured by radionuclide gastric emptying studies. (orig.)

  1. Development of a 2-site radioimmunoassay for antithyroglobulin antibodies using 125I-thyroglobulin

    International Nuclear Information System (INIS)

    Leonard, J.P.; Taymans, F.; Beckers, C.

    1977-01-01

    A 2-site radioassay for human antithyroglobulin auto-antibodies has been developed using human thyroglobulin (Tg) labelled with 125 I. The technique is based on (1) the use of polystyrene tubes coated with Tg, (2) the binding of the antibodies to the solid phase Tg, (3) the reaction of the labelled Tg with the insolubilized antibodies. Factors affecting the assay were evaluated including (a) the effect of the temperature, Tg concentration and coating time on the adsorption of Tg, (b) the stability and storage of the solid phase Tg, (c) the variations in temperature, reaction times and incubation volumes, (d) the effect of the serum proteins, (e) the influence of the variations in concentration and specific activity of the labelled Tg. Increasing sensitivity resulted from a prolonged incubation at low temperature, the addition of serum proteins and the use of an appropriate specific activity of 125 I-Tg. Nonspecific radioactive uptake normally averaged 1% or less of the total radioactivity added. The use of Tg coated tubes makes the technique rapid and simple to be operated. The ability of the coated tubes to be stored and the relative insensitivity of the test to fluctuations in the quality of the tracer represent additional advantages in the routine application of the method. (orig.) [de

  2. Structures of protective antibodies reveal sites of vulnerability on Ebola virus.

    Science.gov (United States)

    Murin, Charles D; Fusco, Marnie L; Bornholdt, Zachary A; Qiu, Xiangguo; Olinger, Gene G; Zeitlin, Larry; Kobinger, Gary P; Ward, Andrew B; Saphire, Erica Ollmann

    2014-12-02

    Ebola virus (EBOV) and related filoviruses cause severe hemorrhagic fever, with up to 90% lethality, and no treatments are approved for human use. Multiple recent outbreaks of EBOV and the likelihood of future human exposure highlight the need for pre- and postexposure treatments. Monoclonal antibody (mAb) cocktails are particularly attractive candidates due to their proven postexposure efficacy in nonhuman primate models of EBOV infection. Two candidate cocktails, MB-003 and ZMAb, have been extensively evaluated in both in vitro and in vivo studies. Recently, these two therapeutics have been combined into a new cocktail named ZMapp, which showed increased efficacy and has been given compassionately to some human patients. Epitope information and mechanism of action are currently unknown for most of the component mAbs. Here we provide single-particle EM reconstructions of every mAb in the ZMapp cocktail, as well as additional antibodies from MB-003 and ZMAb. Our results illuminate key and recurring sites of vulnerability on the EBOV glycoprotein and provide a structural rationale for the efficacy of ZMapp. Interestingly, two of its components recognize overlapping epitopes and compete with each other for binding. Going forward, this work now provides a basis for strategic selection of next-generation antibody cocktails against Ebola and related viruses and a model for predicting the impact of ZMapp on potential escape mutations in ongoing or future Ebola outbreaks.

  3. Influence of vitamin b-12 complex injection (eldervit-12) on ...

    African Journals Online (AJOL)

    Objectives: To assess the effect of vitamin B-12 complex injection on the nephrotoxicity of gentamicin. Design: Experimental study using a pre-validated model. Subject: Adult Swiss albino rats weighing 140-214g, Generic gentamicin sulphate injection and Vitamin B-12complex injection containing 2500mcg ...

  4. Vitamin b 12 supplementation: effects on some biochemical and ...

    African Journals Online (AJOL)

    Phenytoin is known to have some toxicological implications. Vitamin B12 supplementation during phenytoin administration was investigated to assess the benefits and risks of single vitamin supplementation. This study evaluated the biochemical and haematological effects of vitamin B12 on phenytoin toxicity. Twenty-four ...

  5. Simultaneous radiodetermination of folate and vitamin B12

    International Nuclear Information System (INIS)

    Gutcho, S.; Mansbach, L.

    1978-01-01

    The invention concerns a method to simultaneously investigate or determine folate and vitamin B12. The differentiation between both compounds is based on the use of radioactive tracers; a radio-iodized folic acid is used as folate tracer; vitamin B12 can be labelled with 57 Co. (VJ) [de

  6. Vegan Diet, Subnormal Vitamin B-12 Status and Cardiovascular Health

    Directory of Open Access Journals (Sweden)

    Kam S. Woo

    2014-08-01

    Full Text Available Vegetarian diets have been associated with atherosclerosis protection, with healthier atherosclerosis risk profiles, as well as lower prevalence of, and mortality from, ischemic heart disease and stroke. However, there are few data concerning the possible cardiovascular effects of a vegan diet (with no meat, dairy or egg products. Vitamin B-12 deficiency is highly prevalent in vegetarians; this can be partially alleviated by taking dairy/egg products in lact-ovo-vegetarians. However, metabolic vitamin B-12 deficiency is highly prevalent in vegetarians in Australia, Germany, Italy and Austria, and in vegans (80% in Hong Kong and India, where vegans rarely take vitamin B-12 fortified food or vitamin B-12 supplements. Similar deficiencies exist in northern Chinese rural communities consuming inadequate meat, egg or dairy products due to poverty or dietary habits. Vascular studies have demonstrated impaired arterial endothelial function and increased carotid intima-media thickness as atherosclerosis surrogates in such metabolic vitamin B-12 deficient populations, but not in lactovegetarians in China. Vitamin B-12 supplementation has a favourable impact on these vascular surrogates in Hong Kong vegans and in underprivileged communities in northern rural China. Regular monitoring of vitamin B-12 status is thus potentially beneficial for early detection and treatment of metabolic vitamin B-12 deficiency in vegans, and possibly for prevention of atherosclerosis-related diseases.

  7. Vegan diet, subnormal vitamin B-12 status and cardiovascular health.

    Science.gov (United States)

    Woo, Kam S; Kwok, Timothy C Y; Celermajer, David S

    2014-08-19

    Vegetarian diets have been associated with atherosclerosis protection, with healthier atherosclerosis risk profiles, as well as lower prevalence of, and mortality from, ischemic heart disease and stroke. However, there are few data concerning the possible cardiovascular effects of a vegan diet (with no meat, dairy or egg products). Vitamin B-12 deficiency is highly prevalent in vegetarians; this can be partially alleviated by taking dairy/egg products in lact-ovo-vegetarians. However, metabolic vitamin B-12 deficiency is highly prevalent in vegetarians in Australia, Germany, Italy and Austria, and in vegans (80%) in Hong Kong and India, where vegans rarely take vitamin B-12 fortified food or vitamin B-12 supplements. Similar deficiencies exist in northern Chinese rural communities consuming inadequate meat, egg or dairy products due to poverty or dietary habits. Vascular studies have demonstrated impaired arterial endothelial function and increased carotid intima-media thickness as atherosclerosis surrogates in such metabolic vitamin B-12 deficient populations, but not in lactovegetarians in China. Vitamin B-12 supplementation has a favourable impact on these vascular surrogates in Hong Kong vegans and in underprivileged communities in northern rural China. Regular monitoring of vitamin B-12 status is thus potentially beneficial for early detection and treatment of metabolic vitamin B-12 deficiency in vegans, and possibly for prevention of atherosclerosis-related diseases.

  8. Hampered Vitamin B12 Metabolism in Gaucher Disease?

    Directory of Open Access Journals (Sweden)

    Luciana Hannibal PhD

    2017-02-01

    Full Text Available Untreated vitamin B 12 deficiency manifests clinically with hematological abnormalities and combined degeneration of the spinal cord and polyneuropathy and biochemically with elevated homocysteine (Hcy and methylmalonic acid (MMA. Vitamin B 12 metabolism involves various cellular compartments including the lysosome, and a disruption in the lysosomal and endocytic pathways induces functional deficiency of this micronutrient. Gaucher disease (GD is characterized by dysfunctional lysosomal metabolism brought about by mutations in the enzyme beta-glucocerebrosidase (Online Mendelian Inheritance in Man (OMIM: 606463; Enzyme Commission (EC 3.2.1.45, gene: GBA1 . In this study, we collected and examined available literature on the associations between GD, the second most prevalent lysosomal storage disorder in humans, and hampered vitamin B 12 metabolism. Results from independent cohorts of patients show elevated circulating holotranscobalamin without changes in vitamin B 12 levels in serum. Gaucher disease patients under enzyme replacement therapy present normal levels of Hcy and MMA. Although within the normal range, a significant increase in Hcy and MMA with normal serum vitamin B 12 was documented in treated GD patients with polyneuropathy versus treated GD patients without polyneuropathy. Thus, a functional deficiency of vitamin B 12 caused by disrupted lysosomal metabolism in GD is a plausible mechanism, contributing to the neurological form of the disorder but this awaits confirmation. Observational studies suggest that an assessment of vitamin B 12 status prior to the initiation of enzyme replacement therapy may shed light on the role of vitamin B 12 in the pathogenesis and progression of GD.

  9. Effect of iodination site on binding of radiolabeled ligand by insulin antibodies and insulin autoantibodies

    International Nuclear Information System (INIS)

    Diaz, J.L.; Wilkin, T.J.

    1988-01-01

    Four human insulins and four porcine insulins, each monoiodinated to the same specific activity at one of the four tyrosine residues (A14, A19, B16, B26) and purified by reversed-phase liquid chromatography, were tested in a radiobinding assay against a panel of insulin-antibody (IA)-positive sera from 10 insulin-treated diabetics and insulin-autoantibody-positive (IAA) sera from 10 nondiabetics. Of the 10 IAA-positive sera, five were fully cross reactive with both insulin species, and five were specific for human insulin. The rank order of binding of sera with the four ligands from each species was random for IA (mean rank values of 1.9 for A14, 2.0 for A19, 2.5 for B16, and 3.6 for B26 from a possible ranking range of 1 to 4), but more consistent for non-human-insulin-specific IAA (mean rank values 1.3 for A14, 3.8 for A19, 1.7 for B16, and 3.2 for B26 for labeled human insulins; 1.2 for A14, 4.0 for A19, 1.8 for B16, and 3.0 for B26 for labeled porcine insulins). The rank order of binding was virtually uniform for human-insulin-specific IAA (mean values 1.2 for A14, 3.0 for A19, 1.8 for B16, and 4.0 for B26). The influence of iodination site on the binding of labeled insulin appears to be dependent on the proximity of the labeled tyrosine to the antibody binding site and the clonal diversity, or restriction, of insulin-binding antibodies in the test serum. When IA and IAA are measured, the implications of this study regarding the choice of assay ligand may be important

  10. Isolation of recombinant phage antibodies targeting the hemagglutinin cleavage site of highly pathogenic avian influenza virus.

    Directory of Open Access Journals (Sweden)

    Jinhua Dong

    Full Text Available Highly pathogenic avian influenza (HPAI H5N1 viruses, which have emerged in poultry and other wildlife worldwide, contain a characteristic multi-basic cleavage site (CS in the hemagglutinin protein (HA. Because this arginine-rich CS is unique among influenza virus subtypes, antibodies against this site have the potential to specifically diagnose pathogenic H5N1. By immunizing mice with the CS peptide and screening a phage display library, we isolated four antibody Fab fragment clones that specifically bind the antigen peptide and several HPAI H5N1 HA proteins in different clades. The soluble Fab fragments expressed in Escherichia coli bound the CS peptide and the H5N1 HA protein with nanomolar affinity. In an immunofluorescence assay, these Fab fragments stained cells infected with HPAI H5N1 but not those infected with a less virulent strain. Lastly, all the Fab clones could detect the CS peptide and H5N1 HA protein by open sandwich ELISA. Thus, these recombinant Fab fragments will be useful novel reagents for the rapid and specific detection of HPAI H5N1 virus.

  11. Absorption of vitamin B12 and effect of pancreatic juice on gastric vitamin B12 binder in the dog

    International Nuclear Information System (INIS)

    Kasaki, Yukio

    1977-01-01

    The effect of pancreatic juice on vitamin B 12 absorption was studied in dogs. It was found that dog gastric juice as well as pancreatic juice contain vitamin B 12 binding proteins which differ in the elution pattern on DEAE-cellulose columns, the former being eluted at much lower sodium chloride concentrations. When radio-active vitamin B 12 was fed or instilled in the proximal bowel and vitamin B 12 recovered at different bowel levels, it was found that vitamin B 12 -protein complex behaved like gastric juice binder in the proximal bowel and like pancreatic binder in the distal. In vitro digestion of gastric binder with pancreatic juice altered vitamin B 12 -protein complex in such a way that elution pattern became similar to that of pancreatic juice. It was also shown that the change was not due to transfer of vitamin B 12 from gastric binder to pancreatic binder. Trypsin digestion had similar effect on gastric binder, and Sephadex G-200 gelfiltration demonstrated reduction in the molecular size. In the doz, vitamin B 12 first bound to gastric binder undergoes chemical changes in the bowel and becomes a readily absorbable form in the distal bowel. (auth.)

  12. Molecular characterization of monoclonal antibodies that inhibit acetylcholinesterase by targeting the peripheral site and backdoor region.

    Directory of Open Access Journals (Sweden)

    Yves Bourne

    Full Text Available The inhibition properties and target sites of monoclonal antibodies (mAbs Elec403, Elec408 and Elec410, generated against Electrophorus electricus acetylcholinesterase (AChE, have been defined previously using biochemical and mutagenesis approaches. Elec403 and Elec410, which bind competitively with each other and with the peptidic toxin inhibitor fasciculin, are directed toward distinctive albeit overlapping epitopes located at the AChE peripheral anionic site, which surrounds the entrance of the active site gorge. Elec408, which is not competitive with the other two mAbs nor fasciculin, targets a second epitope located in the backdoor region, distant from the gorge entrance. To characterize the molecular determinants dictating their binding site specificity, we cloned and sequenced the mAbs; generated antigen-binding fragments (Fab retaining the parental inhibition properties; and explored their structure-function relationships using complementary x-ray crystallography, homology modeling and flexible docking approaches. Hypermutation of one Elec403 complementarity-determining region suggests occurrence of antigen-driven selection towards recognition of the AChE peripheral site. Comparative analysis of the 1.9Å-resolution structure of Fab408 and of theoretical models of its Fab403 and Fab410 congeners evidences distinctive surface topographies and anisotropic repartitions of charges, consistent with their respective target sites and inhibition properties. Finally, a validated, data-driven docking model of the Fab403-AChE complex suggests a mode of binding at the PAS that fully correlates with the functional data. This comprehensive study documents the molecular peculiarities of Fab403 and Fab410, as the largest peptidic inhibitors directed towards the peripheral site, and those of Fab408, as the first inhibitor directed toward the backdoor region of an AChE and a unique template for the design of new, specific modulators of AChE catalysis.

  13. Vitamin B-12 and Depression: Are They Related?

    Science.gov (United States)

    ... al. Nutritional aspects of depression. Cellular Physiology and Biochemistry. 2015;37:1029. Vitamin B12. Natural Medicines. https:// ... Clinic logo are trademarks of Mayo Foundation for Medical Education and Research. © 1998-2018 Mayo Foundation for ...

  14. Vitamin B12 deficiency: Characterization of psychometrics and MRI morphometrics.

    Science.gov (United States)

    Hsu, Yen-Hsuan; Huang, Ching-Feng; Lo, Chung-Ping; Wang, Tzu-Lan; Tu, Min-Chien

    2016-01-01

    Vitamin B12 is essential for the integrity of the central nervous system. However, performances in different cognitive domains relevant to vitamin B12 deficiency remain to be detailed. To date, there have been limited studies that examined the relationships between cognitions and structural neuroimaging in a single cohort of low-vitamin B12 status. The present study aimed to depict psychometrics and magnetic resonance imaging (MRI) morphometrics among patients with vitamin B12 deficiency, and to examine their inter-relations. We compared 34 consecutive patients with vitamin B12 deficiency (serum level ≤ 250 pg/ml) to 34 demographically matched controls by their cognitive performances and morphometric indices of brain MRI. The correlations between psychometrics and morphometrics were analyzed. The vitamin B12 deficiency group had lower scores than the controls on total scores of Mini-Mental Status Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI) (both P psychometric and morphometric indices, pronounced correlations between bicaudate ratio and long-term memory, mental manipulation, orientation, language, and verbal fluency were noted (all P < 0.01). Vitamin B12 deficiency is associated with a global cognition decline with language, orientation, and mental manipulation selectively impaired. Preferential atrophy in frontal regions is the main neuroimaging feature. Although the frontal ratio highlights the relevant atrophy among patients, the bicaudate ratio might be the best index on the basis of its strong association with global cognition and related cognitive domains, implying dysfunction of fronto-subcortical circuits as the fundamental pathogenesis related to vitamin B12 deficiency.

  15. Vitamin B12 absorption capacity in healthy children

    International Nuclear Information System (INIS)

    Hjelt, K.; Krasilnikoff, P.A.

    1986-01-01

    B12 absorption was investigated in 47 healthy children aged 7 months to 15.8 years (median 4.9 years). The patients had either recovered from giardiasis, the post-gastroenteritis syndrome, or had celiac disease in remission (treated with a gluten-free diet). The B12 absorption was measured by a double-isotope technique using 57 CoB12 and 51 CrCl 3 , the latter being the inabsorbable marker. The radiation dose was minimal. The results were presented as fractional absorption of B12 (FAB12). Within the different age groups, the absorption test was performed by means of the following oral amounts of B12: 0- less than 1 year, 0.5 microgram; 1-3 years: 1.7 micrograms, 4-6 years, 2.5 micrograms; 7-10 years; 3.3 micrograms; and 11-15 years, 4.5 micrograms. When using these oral amounts of B12, the medians (and ranges) of FAB12 were found to be: 1-3 years (n = 18), 37% (16-80%); 4-6 years (n = 10), 27% (19-40%); 7-10 years (n = 9), 32% (21-44%); and 11-15 years (n = 8), 27% (19-59%). The FAB12 in two children aged 7 and 11 months was 31% and 32%, respectively. These results may be interpretated as reference values for B12 absorption in children. Further absorption tests were performed in seven children representing the four age groups from 1 to 15 years. When a high oral amount of B12 was given (i.e., three times the saturation dose), the FAB12 ranged from 0 to 20% (median 9%), whereas a low amount (i.e., one-ninth of the saturation dose) produced fractional absorptions from 65 to 82% (median 74%)

  16. Malabsorption of vitamin B12 in homozygous β-thalassemia

    International Nuclear Information System (INIS)

    Vlachos, P.; Liakakos, D.

    1976-01-01

    Schilling tests were performed in ten children aged 5-12 years suffering from homozygous β-thalassemia. 57 Co labelled vitamin B 12 values excreted in the urine have been found much lower than normal and remained low when the same procedure was repeated with the addition of intrinsic factor. The possible factors responsible for this malabsorption of vitamin B 12 seemed to be liver damage and folic acid deficiency. (orig.) [de

  17. Vitamin B12 absorption capacity in healthy children

    Energy Technology Data Exchange (ETDEWEB)

    Hjelt, K.; Krasilnikoff, P.A.

    1986-03-01

    B12 absorption was investigated in 47 healthy children aged 7 months to 15.8 years (median 4.9 years). The patients had either recovered from giardiasis, the post-gastroenteritis syndrome, or had celiac disease in remission (treated with a gluten-free diet). The B12 absorption was measured by a double-isotope technique using /sup 57/CoB12 and /sup 51/CrCl/sub 3/, the latter being the inabsorbable marker. The radiation dose was minimal. The results were presented as fractional absorption of B12 (FAB12). Within the different age groups, the absorption test was performed by means of the following oral amounts of B12: 0- less than 1 year, 0.5 microgram; 1-3 years: 1.7 micrograms, 4-6 years, 2.5 micrograms; 7-10 years; 3.3 micrograms; and 11-15 years, 4.5 micrograms. When using these oral amounts of B12, the medians (and ranges) of FAB12 were found to be: 1-3 years (n = 18), 37% (16-80%); 4-6 years (n = 10), 27% (19-40%); 7-10 years (n = 9), 32% (21-44%); and 11-15 years (n = 8), 27% (19-59%). The FAB12 in two children aged 7 and 11 months was 31% and 32%, respectively. These results may be interpretated as reference values for B12 absorption in children. Further absorption tests were performed in seven children representing the four age groups from 1 to 15 years. When a high oral amount of B12 was given (i.e., three times the saturation dose), the FAB12 ranged from 0 to 20% (median 9%), whereas a low amount (i.e., one-ninth of the saturation dose) produced fractional absorptions from 65 to 82% (median 74%).

  18. Synthesis and crystal structure of MgB12

    International Nuclear Information System (INIS)

    Adasch, Volker; Hess, Kai-Uwe; Ludwig, Thilo; Vojteer, Natascha; Hillebrecht, Harald

    2006-01-01

    Single crystals of MgB 12 were synthesized from the elements in a Mg/Cu melt at 1600deg. C. MgB 12 crystallizes orthorhombic in space group Pnma with a=16.632(3)A, b=17.803(4)A and c=10.396(2)A. The crystal structure (Z=30, 5796 reflections, 510 variables, R 1 (F)=0.049, wR 2 (I)=0.134) consists of a three dimensional net of B 12 icosahedra and B 21 units in a ratio 2:1. The B 21 units are observed for the first time in a solid compound. Mg is on positions with partial occupation. The summation reveals the composition MgB 12.35 or Mg 0.97 B 12 , respectively. This is in good agreement with the value of MgB 11.25 as expected by electronic reasons to stabilize the boron polyhedra B 12 2- and B 21 4-

  19. [Vitamin B12 Deficiency in Type 2 Diabetes Mellitus].

    Science.gov (United States)

    Tavares Bello, Carlos; Capitão, Ricardo Miguel; Sequeira Duarte, João; Azinheira, Jorge; Vasconcelos, Carlos

    2017-10-31

    Type 2 diabetes mellitus is a common disease, affecting up to 13.1% of the Portuguese population. In addition to the known micro and macrovascular complications, drug side effects constitute a major concern, leading to changes in the treatment guidelines, which favor safety over efficacy. Metformin is the first-line pharmacological treatment for most patients with type 2 diabetes mellitus; however, it has been associated with vitamin B12 deficiency in up to 30% of treated patients. The authors describe the prevalence of vitamin B12 deficiency in a diabetic population and explore the possible underlying factors. Retrospective, observational study. Clinical and laboratory data of type 2 diabetes mellitus patients whose vitamin B12 status was evaluated in the last decade (2005 - 2016) were analyzed. Patients with known malabsorptive syndromes or having undergone bariatric surgery were excluded from the study. Statistical analysis of the data was done and the results were considered statistically significant at p values 2.2 years and 11 ± 10.4 years of type 2 diabetes mellitus duration. These patients had a high prevalence of complications: diabetic renal disease 47.7%, neuropathy 9.2%, retinopathy 14.9%, coronary artery disease 8.4%, cerebrovascular disease 10.9%, and peripheral arterial disease 5.5%. Vitamin B12 deficiency (21.4% of the population and this subgroup was older (68.4 vs 65.8 years, p = 0.006), had a longer type 2 diabetes mellitus duration (13.35 vs 10.36 years; p = 0.001), higher prevalence of retinopathy (20.9% vs 13.3%; p = 0.005) and thyroid dysfunction (34% vs 23.7%; p = 0.002). Vitamin B12 deficiency was also more frequent in patients treated with metformin (24.7% vs 15.8%; p = 0.017), antiplatelet agents (25.4% vs 16.2%, p 26.8% vs 18.2%; p = 0.001). After adjustment for possible confounders, the variables associated with B12 deficiency were: metformin, hypothyroidism, age and type 2 diabetes mellitus duration. Despite the retrospective design

  20. Vitamin B12 and folate deficiency in chronic heart failure.

    Science.gov (United States)

    van der Wal, Haye H; Comin-Colet, Josep; Klip, Ijsbrand T; Enjuanes, Cristina; Grote Beverborg, Niels; Voors, Adriaan A; Banasiak, Waldemar; van Veldhuisen, Dirk J; Bruguera, Jordi; Ponikowski, Piotr; Jankowska, Ewa A; van der Meer, Peter

    2015-02-01

    To determine the prevalence, clinical correlates and the effects on outcome of vitamin B12 and folic acid levels in patients with chronic heart failure (HF). We studied an international pooled cohort comprising 610 patients with chronic HF. The main outcome measure was all-cause mortality. Mean age of the patients was 68±12 years and median serum N-terminal prohormone brain natriuretic peptide level was 1801 pg/mL (IQR 705-4335). Thirteen per cent of the patients had an LVEF >45%. Vitamin B12 deficiency (serum level <200 pg/mL), folate deficiency (serum level <4.0 ng/mL) and iron deficiency (serum ferritin level <100 µg/L, or 100-299 µg/L with a transferrin saturation <20%) were present in 5%, 4% and 58% of the patients, respectively. No significant correlation between mean corpuscular volume and vitamin B12, folic acid or ferritin levels was observed. Lower folate levels were associated with an impaired health-related quality of life (p=0.029). During a median follow-up of 2.10 years (1.31-3.60 years), 254 subjects died. In multivariable proportional hazard models, vitamin B12 and folic acid levels were not associated with prognosis. Vitamin B12 and folate deficiency are relatively rare in patients with chronic HF. Since no significant association was observed between mean corpuscular volume and neither vitamin B12 nor folic acid levels, this cellular index should be used with caution in the differential diagnosis of anaemia in patients with chronic HF. In contrast to iron deficiency, vitamin B12 and folic acid levels were not related to prognosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Vitamin B12 Phosphate Conjugation and Its Effect on Binding to the Human B12 -Binding Proteins Intrinsic Factor and Haptocorrin

    DEFF Research Database (Denmark)

    Ó Proinsias, Keith; Ociepa, Michał; Pluta, Katarzyna

    2016-01-01

    The binding of vitamin B12 derivatives to human B12 transporter proteins is strongly influenced by the type and site of modification of the cobalamin original structure. We have prepared the first cobalamin derivative modified at the phosphate moiety. The reaction conditions were fully optimized...... and its limitations examined. The resulting derivatives, particularly those bearing terminal alkyne and azide groups, were isolated and used in copper-catalyzed alkyne-azide cycloaddition reactions (CuAAC). Their sensitivity towards light revealed their potential as photocleavable molecules. The binding...... abilities of selected derivatives were examined and compared with cyanocobalamin. The interaction of the alkylated derivatives with haptocorrin was less affected than the interaction with intrinsic factor. Furthermore, the configuration of the phosphate moiety was irrelevant to the binding process....

  2. Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25.

    Science.gov (United States)

    Scally, Stephen W; McLeod, Brandon; Bosch, Alexandre; Miura, Kazutoyo; Liang, Qi; Carroll, Sean; Reponen, Sini; Nguyen, Ngan; Giladi, Eldar; Rämisch, Sebastian; Yusibov, Vidadi; Bradley, Allan; Lemiale, Franck; Schief, William R; Emerling, Daniel; Kellam, Paul; King, C Richter; Julien, Jean-Philippe

    2017-11-16

    The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice. Our structural findings reveal the fine specificities associated with two distinct immunogenic sites on Pfs25. Importantly, one of these sites broadly overlaps with the epitope of the well-known 4B7 mouse antibody, which can be targeted simultaneously by antibodies that target a non-overlapping site to additively increase parasite inhibition. Our molecular characterization of inhibitory antibodies informs on the natural disposition of Pfs25 on the surface of ookinetes and provides the structural blueprints to design next-generation immunogens.

  3. Site-specifically {sup 89}Zr-labeled monoclonal antibodies for ImmunoPET

    Energy Technology Data Exchange (ETDEWEB)

    Tinianow, Jeff N.; Gill, Herman S.; Ogasawara, Annie; Flores, Judith E.; Vanderbilt, Alexander N.; Luis, Elizabeth; Vandlen, Richard; Darwish, Martine; Junutula, Jagath R.; Williams, Simon-P. [Genentech Research and Early Development, Genentech Inc., South San Francisco, CA 94080 (United States); Marik, Jan [Genentech Research and Early Development, Genentech Inc., South San Francisco, CA 94080 (United States)], E-mail: marik.jan@gene.com

    2010-04-15

    Three thiol reactive reagents were developed for the chemoselective conjugation of desferrioxamine (Df) to a monoclonal antibody via engineered cysteine residues (thio-trastuzumab). The in vitro stability and in vivo imaging properties of site-specifically radiolabeled {sup 89}Zr-Df-thio-trastuzumab conjugates were investigated. Methods: The amino group of desferrioxamine B was acylated by bromoacetyl bromide, N-hydroxysuccinimidyl iodoacetate, or N-hydroxysuccinimidyl 4-[N-maleimidomethyl]cyclohexane-1-carboxylate to obtain thiol reactive reagents bromoacetyl-desferrioxamine (Df-Bac), iodoacetyl-desferrioxamine (Df-Iac) and maleimidocyclohexyl-desferrioxamine (Df-Chx-Mal), respectively. Df-Bac and Df-Iac alkylated the free thiol groups of thio-trastuzumab by nucleophilic substitution forming Df-Ac-thio-trastuzumab, while the maleimide reagent Df-Chx-Mal reacted via Michael addition to provide Df-Chx-Mal-thio-trastuzumab. The conjugates were radiolabeled with {sup 89}Zr and evaluated for serum stability, and their positron emission tomography (PET) imaging properties were investigated in a BT474M1 (HER2-positive) breast tumor mouse model. Results: The chemoselective reagents were obtained in 14% (Df-Bac), 53% (Df-Iac) and 45% (Df-Chx-Mal) yields. Site-specific conjugation of Df-Chx-Mal to thio-trastuzumab was complete within 1 h at pH 7.5, while Df-Iac and Df-Bac respectively required 2 and 5 h at pH 9. Each Df modified thio-trastuzumab was chelated with {sup 89}Zr in yields exceeding 75%. {sup 89}Zr-Df-Ac-thio-trastuzumab and {sup 89}Zr-Df-Chx-Mal-thio-trastuzumab were stable in mouse serum and exhibited comparable PET imaging capabilities in a BT474M1 (HER2-positive) breast cancer model reaching 20-25 %ID/g of tumor uptake and a tumor to blood ratio of 6.1-7.1. Conclusions: The new reagents demonstrated good reactivity with engineered thiol groups of trastuzumab and very good chelation properties with {sup 89}Zr. The site-specifically {sup 89}Zr-labeled thio-antibodies

  4. Targeted Delivery of LXR Agonist Using a Site-Specific Antibody-Drug Conjugate.

    Science.gov (United States)

    Lim, Reyna K V; Yu, Shan; Cheng, Bo; Li, Sijia; Kim, Nam-Jung; Cao, Yu; Chi, Victor; Kim, Ji Young; Chatterjee, Arnab K; Schultz, Peter G; Tremblay, Matthew S; Kazane, Stephanie A

    2015-11-18

    Liver X receptor (LXR) agonists have been explored as potential treatments for atherosclerosis and other diseases based on their ability to induce reverse cholesterol transport and suppress inflammation. However, this therapeutic potential has been hindered by on-target adverse effects in the liver mediated by excessive lipogenesis. Herein, we report a novel site-specific antibody-drug conjugate (ADC) that selectively delivers a LXR agonist to monocytes/macrophages while sparing hepatocytes. The unnatural amino acid para-acetylphenylalanine (pAcF) was site-specifically incorporated into anti-CD11a IgG, which binds the α-chain component of the lymphocyte function-associated antigen 1 (LFA-1) expressed on nearly all monocytes and macrophages. An aminooxy-modified LXR agonist was conjugated to anti-CD11a IgG through a stable, cathepsin B cleavable oxime linkage to afford a chemically defined ADC. The anti-CD11a IgG-LXR agonist ADC induced LXR activation specifically in human THP-1 monocyte/macrophage cells in vitro (EC50-27 nM), but had no significant effect in hepatocytes, indicating that payload delivery is CD11a-mediated. Moreover, the ADC exhibited higher-fold activation compared to a conventional synthetic LXR agonist T0901317 (Tularik) (3-fold). This novel ADC represents a fundamentally different strategy that uses tissue targeting to overcome the limitations of LXR agonists for potential use in treating atherosclerosis.

  5. Papel da vitamina B12 na patogenia da mielose funicular

    Directory of Open Access Journals (Sweden)

    Horacio M. Canelas

    1965-12-01

    Full Text Available Foi estudada a absorção da vitamina B12 radioativa em 29 casos de mielose funicular. O diagnóstico baseou-se na clássica sintomatologia neu- rológica e na presença de acloridria gástrica e eventuais alterações hemato-lógicas. As manifestações neurológicas foram avaliadas de modo semiquan-titativo e correlacionadas com os resultados do teste de excreção urinária da vitamina B12. Não foi verificada correlação significante da absorção da vitamina B12, quer com a sintomatologia nuerológica total, quer com as síndromes periférica e funicular dorsal. Contudo, foi encontrada significante correlação negativa entre a síndrome piramidal e a absorção da vitamina B12. Os resultados são confrontados com o papel desempenhado pela vitamina B12 na síntese das bainhas de mielina e do ácido ribonuclêico, sendo salientada a importância dêste último para a vida das células nervosas e dos longos axônios.

  6. Identification of differentially expressed proteins in vitamin B 12

    Directory of Open Access Journals (Sweden)

    Swati Varshney

    2015-01-01

    Full Text Available Background: Vitamin B 12 (cobalamin is a water-soluble vitamin generally synthesized by microorganisms. Mammals cannot synthesize this vitamin but have evolved processes for absorption, transport and cellular uptake of this vitamin. Only about 30% of vitamin B 12 , which is bound to the protein transcobalamin (TC (Holo-TC [HoloTC] enters into the cell and hence is referred to as the biologically active form of vitamin B 12 . Vitamin B 12 deficiency leads to several complex disorders, including neurological disorders and anemia. We had earlier shown that vitamin B 12 deficiency is associated with coronary artery disease (CAD in Indian population. In the current study, using a proteomics approach we identified proteins that are differentially expressed in the plasma of individuals with low HoloTC levels. Materials and Methods: We used isobaric-tagging method of relative and absolute quantitation to identify proteins that are differently expressed in individuals with low HoloTC levels when compared to those with normal HoloTC level. Results: In two replicate isobaric tags for relative and absolute quantitation experiments several proteins involved in lipid metabolism, blood coagulation, cholesterol metabolic process, and lipoprotein metabolic process were found to be altered in individuals having low HoloTC levels. Conclusions: Our study indicates that low HoloTc levels could be a risk factor in the development of CAD.

  7. Fluorescent antibody application in bioremediation procedures at the Savannah River Site

    International Nuclear Information System (INIS)

    Brigmon, R.L.; Richardson, B.S.; Franck, M.M.

    1997-01-01

    Direct Fluorescent Antibodies (DFA) and Most Probable Number (MPN) techniques are currently being employed at the Savannah River Site to monitor methanotrophic bacteria for the bioremediation of trichloroethylene (TCE) in field studies. Direct Fluorescent Antibodies were developed against various methanotrophic bacteria isolated from SRS as well as methanotrophic bacteria acquired from the American Type Culture Collection (ATCC). DFA's are anticipated to be more efficient for monitoring methanotroph activity than MPN's because of shorter processing time, lower cost, and the direct nature of the assay. The DFA method is a direct technique, in that samples are processed immediately and can be enumerated within an hour. The MPN method is indirect, since samples must be cultured for 6-8 weeks before measuring methane consumption and carbon dioxide production. Indirect methods are not highly selective and have limited application. The greatest advantage of a faster assay, is that bioremediation procedures utilizing methanotrophic bacteria could be amended. These amendments would be based on environmental monitoring with results in real time (1 hour). The elimination of the MPN technique and the use of DFA's will save significantly on both materials and labor. The data obtained from the DFA's and MPN's were statistically compared to each other and to total bacterial counts (AODC). The statistical analysis used was Analysis of Variants (ANOVA). Using this analysis, groundwater samples were found to be not significantly different; whereas soil were significantly different. These methods were employed on soil samples from the Southern Sector and ground water samples from the TCE-contaminated Sanitary Landfill at SRS. Acridine Orange Direct Counts were compared to show relative differences between total bacterial and methanotroph population

  8. Vitamin B12 absorption judged by measurement of holotranscobalamin, active vitamin B12: evaluation of a commercially available EIA kit.

    Science.gov (United States)

    Greibe, Eva; Nexo, Ebba

    2011-11-01

    Active vitamin B12 absorption is followed by an increase in holotranscobalamin (holoTC) upon loading with a high physiological dose of the vitamin (the CobaSorb test). This study evaluates the use of a newly launched EIA kit for measurement of holoTC (active B12) in relation to the CobaSorb test. Intra-assay imprecision and linearity of the EIA kit was examined, employing serum pools of increasing holoTC concentrations. For the CobaSorb test, holoTC was measured before and after loading with 3-times 9 μg of vitamin B12 employing both the in-house ELISA and the EIA kit (n=25). The EIA kit showed an intra-assay CV between 2.2% and 5.8% for holoTC values ranging from 21 to 80 pmol/L. Employing diluted serum samples resulted in spurious high values of holoTC. The EIA kit performed well in relation to the CobaSorb test and classified the patients studied as capable of absorbing vitamin B12 (n=10) or not (n=15), as did the in-house ELISA. The Active B12 (holoTC) EIA kit proved suitable for use with the CobaSorb test, but not for analysis of diluted serum samples.

  9. Site-Specific Antibody Labeling by Covalent Photoconjugation of Z Domains Functionalized for Alkyne-Azide Cycloaddition Reactions.

    Science.gov (United States)

    Perols, Anna; Arcos Famme, Melina; Eriksson Karlström, Amelie

    2015-11-01

    Antibodies are extensively used in research, diagnostics, and therapy, and for many applications the antibodies need to be labeled. Labeling is typically performed by using amine-reactive probes that target surface-exposed lysine residues, resulting in heterogeneously labeled antibodies. An alternative labeling strategy is based on the immunoglobulin G (IgG)-binding protein domain Z, which binds to the Fc region of IgG. Introducing the photoactivable amino acid benzoylphenylalanine (BPA) into the Z domain makes it possible for a covalent bond to be be formed between the Z domain and the antibody on UV irradiation, to produce a site-specifically labeled product. Z32 BPA was synthesized by solid-phase peptide synthesis and further functionalized to give alkyne-Z32 BPA and azide-Z32 BPA for Cu(I) -catalyzed cycloaddition, as well as DBCO-Z32 BPA for Cu-free strain-promoted cycloaddition. The Z32 BPA variants were conjugated to the human IgG1 antibody trastuzumab and site-specifically labeled with biotin or fluorescein. The fluorescently labeled trastuzumab showed specific staining of the membranes of HER2-expressing cells in immunofluorescence microscopy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Site-specific antibody-drug conjugates: the nexus of bioorthogonal chemistry, protein engineering, and drug development.

    Science.gov (United States)

    Agarwal, Paresh; Bertozzi, Carolyn R

    2015-02-18

    Antibody-drug conjugates (ADCs) combine the specificity of antibodies with the potency of small molecules to create targeted drugs. Despite the simplicity of this concept, generation of clinically successful ADCs has been very difficult. Over the past several decades, scientists have learned a great deal about the constraints on antibodies, linkers, and drugs as they relate to successful construction of ADCs. Once these components are in hand, most ADCs are prepared by nonspecific modification of antibody lysine or cysteine residues with drug-linker reagents, which results in heterogeneous product mixtures that cannot be further purified. With advances in the fields of bioorthogonal chemistry and protein engineering, there is growing interest in producing ADCs by site-specific conjugation to the antibody, yielding more homogeneous products that have demonstrated benefits over their heterogeneous counterparts in vivo. Here, we chronicle the development of a multitude of site-specific conjugation strategies for assembly of ADCs and provide a comprehensive account of key advances and their roots in the fields of bioorthogonal chemistry and protein engineering.

  11. Inhibition of ligand exchange kinetics via active-site trapping with an antibody fragment.

    Science.gov (United States)

    Oyen, David; Steyaert, Jan; Barlow, John N

    2014-04-01

    We describe the first example of an inhibitory antibody fragment (nanobody ca1697) that binds simultaneously to an enzyme (the enzyme dihydrofolate reductase from Escherichia coli) and its bound substrate (folate). Binding of the antibody to the substrate causes a 20-fold reduction in the rate of folate exchange kinetics. This work opens up the prospect of designing new types of antibody-based inhibitors of enzymes and receptors through suitable design of immunogens.

  12. Evaluation of vitamin B 12 deficiency in various clinical condition

    International Nuclear Information System (INIS)

    Baig, J.A.; Alam, J.M.; Kazmi, T.; Waseem, S.; Hussain, A.; Arif, S.; Shaheen, R.; Sultana, I.

    2010-01-01

    Low levels of vitamin B 12 have been associated with several clinical conditions. However no single symptom or group of symptoms can be made responsible. Reported causes of deficiency among older population are hematologic or neurological, followed by gastrointestinal and possibly vascular symptoms. The present prospective observational study was, hence, initiated to evaluate the underlying clinical condition or symptoms associated with vitamin B12 deficiency. The study was prospective observational and carried out on 121 patients (males, n=63 and females, n=58) for the period from January 1, 2004 to January 24, 2007. Age ranges were between 16 - 70 years, and categorized as > 60 yrs and < 60 years. All blood parameters were analyzed by standardized methods on automated analyzers. The deficiency was found to be more prevalent in males and increased from 52.06% to 58.10% in individuals with vitamin B12 <150 pg/ml. Mal nourishment was noted among the most subjects and weakness and anemia were frequent clinical findings (35.55%, n=43, 14%, n=51). Other clinical conditions were neuropsychiatric. Whereas less frequent findings were paraesthesia and gastrointestinal symptoms. Hypertension was more prevalent in vitamin B12 deficient individuals followed by diabetes, dementia, stroke, ischemic heart disease and Parkinson's disease. (author)

  13. 32 CFR 806b.12 - Requesting the Social Security Number.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Requesting the Social Security Number. 806b.12... Number. When asking an individual for his or her Social Security Number, always give a Privacy Act... Social Security Number; and whether providing the Social Security Number is voluntary or mandatory. Do...

  14. The Ligand Substitution Reactions of Hydrophobic Vitamin B12 ...

    African Journals Online (AJOL)

    South African Journal of Chemistry ... The equilibrium constants, K, for the reaction of five-membered heterocyclic nitrogenous bases (the azoles imidazole, pyrazole and 1,2,4-triazole) with displacement of ... Keywords: Hydrophobic vitamin B12, cobalt corrinoids, equilibrium constants, solvent polarity, trans influence.

  15. Dietary sources of vitamin B-12 and their association with vitamin B-12 status markers in healthy older adults in the B-PROOF study

    NARCIS (Netherlands)

    Brouwer-Brolsma, E.M.; Dhonukshe-Rutten, R.A.M.; Wijngaarden, van J.P.; Zwaluw, van der N.L.; Velde, van der N.; Groot, de C.P.G.M.

    2015-01-01

    Low vitamin B-12 concentrations are frequently observed among older adults. Malabsorption is hypothesized to be an important cause of vitamin B-12 inadequacy, but serum vitamin B-12 may also be differently affected by vitamin B-12 intake depending on food source. We examined associations between

  16. Dietary Sources of Vitamin B-12 and Their Association with Vitamin B-12 Status Markers in Healthy Older Adults in the B-PROOF Study

    NARCIS (Netherlands)

    Brouwer-Brolsma, Elske M.; Dhonukshe-Rutten, Rosalie A. M.; van Wijngaarden, Janneke P.; Zwaluw, Nikita L. van der; Velde, Nathalie van der; de Groot, Lisette C. P. G. M.

    2015-01-01

    Low vitamin B-12 concentrations are frequently observed among older adults. Malabsorption is hypothesized to be an important cause of vitamin B-12 inadequacy, but serum vitamin B-12 may also be differently affected by vitamin B-12 intake depending on food source. We examined associations between

  17. Dietary sources of vitamin B-12 and their association with vitamin B-12 status markers in healthy older adults in the B-PROOF study

    NARCIS (Netherlands)

    E.M. Brouwer-Brolsma (Elske); R.A.M. Dhonukshe-Rutten (Rosalie); J.P. van Wijngaarden (Janneke); N.L. van der Zwaluw (N.); N. van der Velde (Nathalie); L.C.P.G.M. de Groot (Lisette)

    2015-01-01

    textabstractLow vitamin B-12 concentrations are frequently observed among older adults. Malabsorption is hypothesized to be an important cause of vitamin B-12 inadequacy, but serum vitamin B-12 may also be differently affected by vitamin B-12 intake depending on food source. We examined associations

  18. Modeling the reactions catalyzed by coenzyme B12-dependent enzymes.

    Science.gov (United States)

    Sandala, Gregory M; Smith, David M; Radom, Leo

    2010-05-18

    Enzymes accelerate chemical reactions with an exceptional selectivity that makes life itself possible. Understanding the factors responsible for this efficient catalysis is of utmost importance in our quest to harness the tremendous power of enzymes. Computational chemistry has emerged as an important adjunct to experimental chemistry and biochemistry in this regard, because it provides detailed insights into the relationship between structure and function in a systematic and straightforward manner. In this Account, we highlight our recent high-level theoretical investigations toward this end in studying the radical-based reactions catalyzed by enzymes dependent on coenzyme B(12) (or adenosylcobalamin, AdoCbl). In addition to their fundamental position in biology, the AdoCbl-dependent enzymes represent a valuable framework within which to understand Nature's method of efficiently handling high-energy species to execute very specific reactions. The AdoCbl-mediated reactions are characterized by the interchange of a hydrogen atom and a functional group on adjacent carbon atoms. Our calculations are consistent with the conclusion that the main role of AdoCbl is to provide a source of radicals, thus moving the 1,2-rearrangements onto the radical potential energy surface. Our studies also show that the radical rearrangement step is facilitated by partial proton transfer involving the substrate. Specifically, we observe that the energy requirements for radical rearrangement are reduced dramatically with appropriate partial protonation or partial deprotonation or sometimes (synergistically) both. Such interactions are particularly relevant to enzyme catalysis, because it is likely that the local amino acid environment in the active site of an enzyme can function in this capacity through hydrogen bonding. Finally, our calculations indicate that the intervention of a very stable radical along the reaction pathway may inactivate the enzyme, demonstrating that sustained

  19. Topography of the high-affinity lysine binding site of plasminogen as defined with a specific antibody probe

    International Nuclear Information System (INIS)

    Miles, L.A.; Plow, E.F.

    1986-01-01

    An antibody population that reacted with the high-affinity lysine binding site of human plasminogen was elicited by immunizing rabbits with an elastase degradation product containing kringles 1-3 (EDP I). This antibody was immunopurified by affinity chromatography on plasminogen-Sepharose and elution with 0.2 M 6-aminohexanoic acid. The eluted antibodies bound [ 125 I]EDP I, [ 125 I]Glu-plasminogen, and [ 125 I]Lys-plasminogen in radioimmunoassays, and binding of each ligand was at least 99% inhibited by 0.2 M 6-aminohexanoic acid. The concentrations for 50% inhibition of [ 125 I]EDP I binding by tranexamic acid, 6-aminohexanoic acid, and lysine were 2.6, 46, and l730 μM, respectively. Similar values were obtained with plasminogen and suggested that an unoccupied high-affinity lysine binding site was required for antibody recognition. The antiserum reacted exclusively with plasminogen derivatives containing the EDP I region and did not react with those lacking an EDP I region, or with tissue plasminogen activator or prothrombin, which also contains kringles. By immunoblotting analyses, a chymotryptic degradation product of M/sub r/ 20,000 was derived from EDP I that retained reactivity with the antibody. α 2 -Antiplasmin inhibited the binding of radiolabeled EDP I, Glu-plasminogen, or Lys-plasminogen by the antiserum, suggesting that the recognized site is involved in the noncovalent interaction of the inhibitor with plasminogen. The binding of [ 125 I]EDP I to fibrin was also inhibited by the antiserum. The observations provide independent evidence for the role of the high-affinity lysine binding site in the functional interactions of plasminogen with its primary substrate and inhibitor

  20. Dipstick based immunochemiluminescence biosensor for the analysis of vitamin B12 in energy drinks: A novel approach

    International Nuclear Information System (INIS)

    Selvakumar, L.S.; Thakur, M.S.

    2012-01-01

    Graphical abstract: (a) Schematic representation of immunochemiluminescence based dipstick technique for detection of vitamin B 12 . (b) Enzymatic dephosphorylation of dioxetane by alkaline phosphatase. Highlights: ► Dipstick based immunochemiluminescence biosensor proposed for vitamin B 12 analysis. ► The limit of detection of vitamin B 12 is 1 ng mL −1 and applied in energy drinks. ► Chemiluminescence generated was inversely proportional to vitamin B 12 concentration. ► Chemiluminescence analytical procedure was compared with ELISA. ► Alkaline phosphatase was stable chemiluminescent enzyme than Horse Radish Peroxidase. - Abstract: In this article, we describe a dipstick based immunochemiluminescence (immuno-CL) biosensor for the detection of vitamin B 12 in energy drinks. The method is a direct competitive type format involving the immobilization of vitamin B 12 antibody on nitrocellulose membrane (NC) followed by treatment with vitamin B 12 and vitamin B 12 –alkaline phosphatase conjugate to facilitate the competitive binding. The dipstick was further treated with substrate disodium 2-chloro-5-(4-methoxyspiro {1,2-dioxetane-3,2¢-(5¢-chloro)tricyclo[3.3.1.13,7]decan}-4-yl)-1-phenyl phosphate (CDP-Star) to generate chemiluminescence (CL). The number of photons generated was inversely proportional to the vitamin B 12 concentration. After systematic optimization, the limit of detection was 1 ng mL −1 . The coefficient of variation was below 0.2% for both intra- and inter-assay precision. Vitamin B 12 was extracted from energy drinks with recovery ranged from 90 to 99.4%. Two different energy drinks samples were analyzed, and a good correlation was observed when the data were compared with a reference enzyme linked immuno sorbent assay (ELISA) method. The developed method is suitable for an accurate, sensitive, and high-throughput screening of vitamin B 12 in energy drinks samples. The dipstick technique based on immuno-CL is suitable for the

  1. Site-directed antibody immobilization using a protein A-gold binding domain fusion protein for enhanced SPR immunosensing.

    Science.gov (United States)

    de Juan-Franco, Elena; Caruz, Antonio; Pedrajas, J R; Lechuga, Laura M

    2013-04-07

    We have implemented a novel strategy for the oriented immobilization of antibodies onto a gold surface based on the use of a fusion protein, the protein A-gold binding domain (PAG). PAG consists of a gold binding peptide (GBP) coupled to the immunoglobulin-binding domains of staphylococcal protein A. This fusion protein provides an easy and fast oriented immobilization of antibodies preserving its native structure, while leaving the antigen binding sites (Fab) freely exposed. Using this immobilization strategy, we have demonstrated the performance of the immunosensing of the human Growth Hormone by SPR. A limit of detection of 90 ng mL(-1) was obtained with an inter-chip variability lower than 7%. The comparison of this method with other strategies for the direct immobilization of antibodies over gold surfaces has showed the enhanced sensitivity provided by the PAG approach.

  2. Towards On-site Pathogen Detection Using Antibody-based Sensors

    DEFF Research Database (Denmark)

    Skottrup, Peter Durand; Nicolaisen, Mogens; Justesen, Annemarie Fejer

    2008-01-01

    In this paper the recent progress within biosensors for plant pathogen detection will be reviewed. Bio-recognition layers on sensors can be designed in various ways, however the most popular approach is to immobilise antibodies for specific capture of analytes. Focus will be put on antibody surfa...

  3. Forms and Amounts of Vitamin B12 in Infant Formula: A Pilot Study

    DEFF Research Database (Denmark)

    Greibe, Eva; Nexø, Ebba

    2016-01-01

    12 (cyano-B12). Here we test commercially available infant formulas. METHODS: Eleven commercially available infant formulas were measured for content of B12 and analyzed for the presence of B12-binding proteins and forms of B12 using size exclusion chromatography and HPLC. RESULTS: All infant...... formulas contained B12 by and large in accord with the informations given on the package inserts. None of the formulas contained protein-bound B12, and cyano-B12 accounted for 19-78% of the total amount of B12 present, while hydroxo-B12 constituted more or less the rest. CONCLUSIONS: This pilot study shows...... that infant formula differs from breast milk in providing the infant with free B12, rather than protein-bound B12, and by a relative high content of cyano-B12. The consequence of supplying the infant with synthetic cyano-B12 remains to be elucidated....

  4. Vegetarer har høj risiko for at få B12-vitaminmangel

    DEFF Research Database (Denmark)

    Javid, Parva; Christensen, Erik

    2016-01-01

    Since vegetarians have a lower intake of vitamin B12 (B12) than non-vegetarians, they are at increased risk of developing B12 deficiency. The less animal products the food contains the worse the B12 status. However, even lacto-ovo-vegetarians run the risk of becoming deficient in B12. Vegetarians...... are recommended regularly to take supplements of B12, and they should be informed of the lacking content of B12 of plant products and the hazards of B12 deficiency. Furthermore, vegetarians should routinely be checked for possible B12 deficiency....

  5. The human serum metabolome of vitamin B-12 deficiency and repletion, and associations with neurological function

    Science.gov (United States)

    We characterize the human serum metabolome in sub-clinical vitamin B-12 (B-12) deficiency and repletion. A pre-post treatment study provided one injection of 10 mg B-12 to 27 community-dwelling elderly Chileans with B-12 deficiency evaluated with serum B-12, plasma homocysteine, methylmalonic acid a...

  6. The tinker, tailor, soldier in intracellular B12 trafficking.

    Science.gov (United States)

    Banerjee, Ruma; Gherasim, Carmen; Padovani, Dominique

    2009-10-01

    The recognition of eight discrete genetic complementation groups among patients with inherited cobalamin disorders provided early insights into the complexity of a cofactor-processing pathway that supports only two known B(12)-dependent enzymes in mammals. With the identification of all eight genes now completed, biochemical interrogations of their functions have started and are providing novel insights into a trafficking pathway involving porters that tinker with and tailor the active cofactor forms and editors that ensure the fidelity of the cofactor loading process. The principles of sequestration and escorted delivery of a rare and reactive organometallic cofactor that are emerging from studies on B(12) might be of general relevance to other cofactor trafficking pathways.

  7. Forms of vitamin B12 in radioisotope dilution assays

    International Nuclear Information System (INIS)

    Begley, J.A.; Hall, C.A.

    1981-01-01

    Since the presence of analogues of vitamin B 12 (B 12 , cobalamin, Cbl) has been postulated as the basis for the high values obtained by some radioisotope dilution assays (RIDA) of serum Cbl, serum was examined for analogues. None could be demonstrated in the extracts of serum prepared for RIDA as sought by both direct and indirect techniques. The natural forms of serum Cbl were converted to cyanocobalamin (CN Cbl) by this process of extraction which included cyanide (CN). The correctly performed RIDA for Cbl based on R binder gave higher values than a RIDA based on intrinsic factor or than by bioassay. By exclusion, the difference appeared to be due to unidentified factors rather than the presence of analogues. (author)

  8. Vitamin B12 deficiency presenting as acute ataxia.

    Science.gov (United States)

    Crawford, John Ross; Say, Daphne

    2013-03-26

    A previously healthy 7-year-old Caucasian boy was hospitalised for evaluation of acute ataxia and failure to thrive, initially suspicious for an intracranial mass. Weight and body mass index were below the third percentile and he demonstrated loss of joint position and vibratory sense on examination. Laboratory studies revealed megaloblastic anaemia while an initial MRI of the brain showed no evidence of mass lesions or other abnormalities. A dietary history revealed the child subscribed to a restrictive vegan diet with little to no intake of animal products or other fortified foods. The child was diagnosed with presumed vitamin B12 deficiency and was treated with intramuscular B12 injections. Neurological symptoms resolved promptly within several days after starting therapy. This case underlines the importance of assessing nutritional status in the evaluation of neurological dysfunction in the pediatric patient.

  9. [Neurological signs due to isolated vitamin B12 deficiency].

    Science.gov (United States)

    Martinez Estrada, K M; Cadabal Rodriguez, T; Miguens Blanco, I; García Méndez, L

    2013-01-01

    Isolated vitamin B12 deficiency is a common condition in elderly patients but uncommon in patients younger than 30 years, with an average age of onset between 60 and 70 years. This is because the dietary cobalamin, which is normally split by enzymes in meat in the presence of hydrochloric acid and pepsin in the stomach, is not released in the stomachs of elderly patients, usually due to achlorhydria. Although the body may be unable to release cobalamin it does retain the ability to absorb vitamin B12 in its crystalline form, which is present in multivitamin preparations. Other causes are due to drugs that suppress gastric acid production. Neurological signs of vitamin B12 deficiency can occur in patients with a normal haematocrit and red cell indices. They include paresthesia, loss of sensation and strength in the limbs, and ataxia. Reflexes may be slowed down or increased. Romberg and Babinsky signs may be positive, and vibration and position sensitivity often decreases. Behavoural disorders range from irritability and memory loss to severe dementia. The symptoms often do not fully respond to treatment. A case is presented of an isolated vitamin B12 deficiency in 27 year-old female patient who was seen in primary health care. During anamnesis she mentioned low back pain, to which she attributed the loss of strength and tenderness in the right side of the body, as well as the slow and progressive onset of accompanied headache for the previous 4 days. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  10. Vitamin B12 among Vegetarians: Status, Assessment and Supplementation.

    Science.gov (United States)

    Rizzo, Gianluca; Laganà, Antonio Simone; Rapisarda, Agnese Maria Chiara; La Ferrera, Gioacchina Maria Grazia; Buscema, Massimo; Rossetti, Paola; Nigro, Angela; Muscia, Vincenzo; Valenti, Gaetano; Sapia, Fabrizio; Sarpietro, Giuseppe; Zigarelli, Micol; Vitale, Salvatore Giovanni

    2016-11-29

    Cobalamin is an essential molecule for humans. It acts as a cofactor in one-carbon transfers through methylation and molecular rearrangement. These functions take place in fatty acid, amino acid and nucleic acid metabolic pathways. The deficiency of vitamin B12 is clinically manifested in the blood and nervous system where the cobalamin plays a key role in cell replication and in fatty acid metabolism. Hypovitaminosis arises from inadequate absorption, from genetic defects that alter transport through the body, or from inadequate intake as a result of diet. With the growing adoption of vegetarian eating styles in Western countries, there is growing focus on whether diets that exclude animal foods are adequate. Since food availability in these countries is not a problem, and therefore plant foods are sufficiently adequate, the most delicate issue remains the contribution of cobalamin, which is poorly represented in plants. In this review, we will discuss the status of vitamin B12 among vegetarians, the diagnostic markers for the detection of cobalamin deficiency and appropriate sources for sufficient intake, through the description of the features and functions of vitamin B12 and its absorption mechanism.

  11. Vitamin B12 among Vegetarians: Status, Assessment and Supplementation

    Directory of Open Access Journals (Sweden)

    Gianluca Rizzo

    2016-11-01

    Full Text Available Cobalamin is an essential molecule for humans. It acts as a cofactor in one-carbon transfers through methylation and molecular rearrangement. These functions take place in fatty acid, amino acid and nucleic acid metabolic pathways. The deficiency of vitamin B12 is clinically manifested in the blood and nervous system where the cobalamin plays a key role in cell replication and in fatty acid metabolism. Hypovitaminosis arises from inadequate absorption, from genetic defects that alter transport through the body, or from inadequate intake as a result of diet. With the growing adoption of vegetarian eating styles in Western countries, there is growing focus on whether diets that exclude animal foods are adequate. Since food availability in these countries is not a problem, and therefore plant foods are sufficiently adequate, the most delicate issue remains the contribution of cobalamin, which is poorly represented in plants. In this review, we will discuss the status of vitamin B12 among vegetarians, the diagnostic markers for the detection of cobalamin deficiency and appropriate sources for sufficient intake, through the description of the features and functions of vitamin B12 and its absorption mechanism.

  12. Antithyroglobulin antibody

    Science.gov (United States)

    Thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Hypothyroidism - thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Graves disease - thyroglobulin antibody; Underactive thyroid - thyroglobulin antibody

  13. Brucella melitensis VirB12 recombinant protein is a potential marker for serodiagnosis of human brucellosis.

    Science.gov (United States)

    Mirkalantari, Shiva; Zarnani, Amir-Hassan; Nazari, Mahboobeh; Irajian, Gholam Reza; Amirmozafari, Nour

    2017-03-03

    The numerous drawbacks of current serological tests for diagnosis of brucellosis which mainly results from cross reactivity with LPS from other gram-negative bacteria have generated an increasing interest to find more specific non-LPS antigens. Previous studies had indicated that Brucella VirB12 protein, a cell surface protein and component of type IV secretion system, induces antibody response during animal infection. However, this protein has not yet been tested as a serological diagnostic marker in human brucellosis. Recombinant VirB12 protein was prepared and evaluated the efficacy of it in an indirect enzyme-linked immunosorbent assay (ELISA) for brucellosis with sera collected from different region of Iran and the results were compared with a commercial ELISA kit. Sera from human brucellosis patients strongly reacted to the purified recombinant VirB12. The sensitivity, specificity, accuracy, negative predictive value and positive predictive value of recombinant VirB12-based ELISA related to the commercial-ELISA method were 87.8, 94, 90, 80 and 96.6% respectively. We concluded that antigenic VirB12 have a property value that can be considered as a candidate for using in serodiagnostic tests for human brucellosis.

  14. Attachment Site Cysteine Thiol pKa Is a Key Driver for Site-Dependent Stability of THIOMAB Antibody-Drug Conjugates.

    Science.gov (United States)

    Vollmar, Breanna S; Wei, Binqing; Ohri, Rachana; Zhou, Jianhui; He, Jintang; Yu, Shang-Fan; Leipold, Douglas; Cosino, Ely; Yee, Sharon; Fourie-O'Donohue, Aimee; Li, Guangmin; Phillips, Gail L; Kozak, Katherine R; Kamath, Amrita; Xu, Keyang; Lee, Genee; Lazar, Greg A; Erickson, Hans K

    2017-10-18

    The incorporation of cysteines into antibodies by mutagenesis allows for the direct conjugation of small molecules to specific sites on the antibody via disulfide bonds. The stability of the disulfide bond linkage between the small molecule and the antibody is highly dependent on the location of the engineered cysteine in either the heavy chain (HC) or the light chain (LC) of the antibody. Here, we explore the basis for this site-dependent stability. We evaluated the in vivo efficacy and pharmacokinetics of five different cysteine mutants of trastuzumab conjugated to a pyrrolobenzodiazepine (PBD) via disulfide bonds. A significant correlation was observed between disulfide stability and efficacy for the conjugates. We hypothesized that the observed site-dependent stability of the disulfide-linked conjugates could be due to differences in the attachment site cysteine thiol pK a . We measured the cysteine thiol pK a using isothermal titration calorimetry (ITC) and found that the variants with the highest thiol pK a (LC K149C and HC A140C) were found to yield the conjugates with the greatest in vivo stability. Guided by homology modeling, we identified several mutations adjacent to LC K149C that reduced the cysteine thiol pK a and, thus, decreased the in vivo stability of the disulfide-linked PBD conjugated to LC K149C. We also present results suggesting that the high thiol pK a of LC K149C is responsible for the sustained circulation stability of LC K149C TDCs utilizing a maleimide-based linker. Taken together, our results provide evidence that the site-dependent stability of cys-engineered antibody-drug conjugates may be explained by interactions between the engineered cysteine and the local protein environment that serves to modulate the side-chain thiol pK a . The influence of cysteine thiol pK a on stability and efficacy offers a new parameter for the optimization of ADCs that utilize cysteine engineering.

  15. Dietary Sources of Vitamin B-12 and Their Association with Vitamin B-12 Status Markers in Healthy Older Adults in the B-PROOF Study

    Directory of Open Access Journals (Sweden)

    Elske M. Brouwer-Brolsma

    2015-09-01

    Full Text Available Low vitamin B-12 concentrations are frequently observed among older adults. Malabsorption is hypothesized to be an important cause of vitamin B-12 inadequacy, but serum vitamin B-12 may also be differently affected by vitamin B-12 intake depending on food source. We examined associations between dietary sources of vitamin B-12 (meat, fish and shellfish, eggs, dairy and serum vitamin B-12, using cross-sectional data of 600 Dutch community-dwelling adults (≥65 years. Dietary intake was assessed with a validated food frequency questionnaire. Vitamin B-12 concentrations were measured in serum. Associations were studied over tertiles of vitamin B-12 intake using P for trend, by calculating prevalence ratios (PRs, and splines. Whereas men had significantly higher vitamin B-12 intakes than women (median (25th–75th percentile: 4.18 (3.29–5.38 versus 3.47 (2.64–4.40 μg/day, serum vitamin B-12 did not differ between the two sexes (mean ± standard deviation (SD: 275 ± 104 pmol/L versus 290 ± 113 pmol/L. Higher intakes of dairy, meat, and fish and shellfish were significantly associated with higher serum vitamin B-12 concentrations, where meat and dairy—predominantly milk were the most potent sources. Egg intake did not significantly contribute to higher serum vitamin B-12 concentrations. Thus, dairy and meat were the most important contributors to serum vitamin B-12, followed by fish and shellfish.

  16. Molecular evolution of broadly neutralizing Llama antibodies to the CD4-binding site of HIV-1.

    Science.gov (United States)

    McCoy, Laura E; Rutten, Lucy; Frampton, Dan; Anderson, Ian; Granger, Luke; Bashford-Rogers, Rachael; Dekkers, Gillian; Strokappe, Nika M; Seaman, Michael S; Koh, Willie; Grippo, Vanina; Kliche, Alexander; Verrips, Theo; Kellam, Paul; Fassati, Ariberto; Weiss, Robin A

    2014-12-01

    To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols.

  17. [Stability of folic acid and vitamin B12 in TPN].

    Science.gov (United States)

    Almodóvar, M J; Hernández Jaras, M V; León-Sanz, M; Ortuño, B; Estenoz, J; Negro Vega, E; Marfagón, N; Herreros de Tejada, A

    1991-01-01

    The stability of folic acid (FA) in mixtures of Total Parenteral Nutrition has been and is a controversial subject, with discussion concerning the influence of factors such as temperature, light and storage time. As regards the stability of the vitamin B12, there are few studies in scientific literature. For all those reasons, we consider it necessary to make a proper study to evaluate the influence of different factors in the stability of both vitamins. The study was made on 3 liter TPN bags of the EVA type, the composition of which was as follows: AA (85g), glucosa (225g), fat (50g), Na (86mEq), K (60 mEq), Ca (15 mEq), Cl (90 mEq), P (17 mmol) acetate (149 mEq) and 10 ml of MVI-12 which contain 400 micrograms of PA and 5 micrograms of Vitamin B 12. Consideration was also given to the stability of these two vitamins in the same diet, to which were added 10 ml of a commercial preparation of oligo-elements. Six TPN bags were prepared (without oligo-elements); two of them were kept in a fridge and protected from the light, two were kept at room temperature and protected from the light and the other two at room temperature without protection from the light. Samples were taken from all the bags immediately after their preparation and after 24, 48, 72 and 96 hours. The same process was carried with other TPN bags which did contain oligo-elements. The method for determining FA and Vitamin B12 was by radioassay.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Site-specific chemical modification of antibody fragments using traceless cleavable linkers.

    Science.gov (United States)

    Bernardes, Gonçalo J L; Steiner, Martina; Hartmann, Isabelle; Neri, Dario; Casi, Giulio

    2013-11-01

    Antibody-drug conjugates (ADCs) are promising agents for the selective delivery of cytotoxic drugs to specific cells (for example, tumors). In this protocol, we describe two strategies for the precise modification at engineered C- or N-terminal cysteines of antibodies in IgG, diabody and small immunoprotein (SIP) formats that yield homogenous ADCs. In this protocol, cemadotin derivatives are used as model drugs, as these agents have a potent cytotoxic activity and are easy to synthesize. However, other drugs with similar functional groups could be considered. In the first approach, a cemadotin derivative containing a sulfhydryl group results in a mixed disulfide linkage. In the second approach, a cemadotin derivative containing an aldehyde group is joined via a thiazolidine linkage. The procedures outlined are robust, enabling the preparation of ADCs with a defined number of drugs per antibody in a time frame between 7 and 24 h.

  19. Forms and Amounts of Vitamin B12 in Infant Formula: A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Eva Greibe

    Full Text Available Infant formula is based on cow's milk and designed to mimic breast milk for substitution. Vitamin B12 (B12 is bound to proteins in both breast milk and cow's milk, and in milk from both species the vitamin occurs mainly in its natural form such as hydroxo-B12 with little or no synthetic B12 (cyano-B12. Here we test commercially available infant formulas.Eleven commercially available infant formulas were measured for content of B12 and analyzed for the presence of B12-binding proteins and forms of B12 using size exclusion chromatography and HPLC.All infant formulas contained B12 by and large in accord with the informations given on the package inserts. None of the formulas contained protein-bound B12, and cyano-B12 accounted for 19-78% of the total amount of B12 present, while hydroxo-B12 constituted more or less the rest.This pilot study shows that infant formula differs from breast milk in providing the infant with free B12, rather than protein-bound B12, and by a relative high content of cyano-B12. The consequence of supplying the infant with synthetic cyano-B12 remains to be elucidated.

  20. Forms and Amounts of Vitamin B12 in Infant Formula: A Pilot Study.

    Science.gov (United States)

    Greibe, Eva; Nexo, Ebba

    2016-01-01

    Infant formula is based on cow's milk and designed to mimic breast milk for substitution. Vitamin B12 (B12) is bound to proteins in both breast milk and cow's milk, and in milk from both species the vitamin occurs mainly in its natural form such as hydroxo-B12 with little or no synthetic B12 (cyano-B12). Here we test commercially available infant formulas. Eleven commercially available infant formulas were measured for content of B12 and analyzed for the presence of B12-binding proteins and forms of B12 using size exclusion chromatography and HPLC. All infant formulas contained B12 by and large in accord with the informations given on the package inserts. None of the formulas contained protein-bound B12, and cyano-B12 accounted for 19-78% of the total amount of B12 present, while hydroxo-B12 constituted more or less the rest. This pilot study shows that infant formula differs from breast milk in providing the infant with free B12, rather than protein-bound B12, and by a relative high content of cyano-B12. The consequence of supplying the infant with synthetic cyano-B12 remains to be elucidated.

  1. Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jinghe; Kang, Byong H.; Ishida, Elise; Zhou, Tongqing; Griesman, Trevor; Sheng, Zizhang; Wu, Fan; Doria-Rose, Nicole A.; Zhang, Baoshan; McKee, Krisha; O’Dell, Sijy; Chuang, Gwo-Yu; Druz, Aliaksandr; Georgiev, Ivelin S.; Schramm, Chaim A.; Zheng, Anqi; Joyce, M.  Gordon; Asokan, Mangaiarkarasi; Ransier, Amy; Darko, Sam; Migueles, Stephen A.; Bailer, Robert T.; Louder, Mark K.; Alam, S.  Munir; Parks, Robert; Kelsoe, Garnett; Von Holle, Tarra; Haynes, Barton F.; Douek, Daniel C.; Hirsch, Vanessa; Seaman, Michael S.; Shapiro, Lawrence; Mascola, John R.; Kwong, Peter D.; Connors, Mark

    2016-11-01

    Detailed studies of the broadly neutralizing antibodies (bNAbs) that underlie the best available examples of the humoral immune response to HIV are providing important information for the development of therapies and prophylaxis for HIV-1 infection. Here, we report a CD4-binding site (CD4bs) antibody, named N6, that potently neutralized 98% of HIV-1 isolates, including 16 of 20 that were resistant to other members of its class. N6 evolved a mode of recognition such that its binding was not impacted by the loss of individual contacts across the immunoglobulin heavy chain. In addition, structural analysis revealed that the orientation of N6 permitted it to avoid steric clashes with glycans, which is a common mechanism of resistance. Thus, an HIV-1-specific bNAb can achieve potent, near-pan neutralization of HIV-1, making it an attractive candidate for use in therapy and prophylaxis.

  2. Vitamin B-12 supplementation during pregnancy and early lactation increases maternal, breast milk, and infant measures of vitamin B-12 status.

    Science.gov (United States)

    Duggan, Christopher; Srinivasan, Krishnamachari; Thomas, Tinku; Samuel, Tinu; Rajendran, Ramya; Muthayya, Sumithra; Finkelstein, Julia L; Lukose, Ammu; Fawzi, Wafaie; Allen, Lindsay H; Bosch, Ronald J; Kurpad, Anura V

    2014-05-01

    Pregnant women in resource-poor areas are at risk of multiple micronutrient deficiencies, and indicators of low vitamin B-12 status have been associated with adverse pregnancy outcomes, including anemia, low birth weight, and intrauterine growth retardation. To evaluate whether daily oral vitamin B-12 supplementation during pregnancy increases maternal and infant measures of vitamin B-12 status, we performed a randomized, placebo-controlled clinical trial. Pregnant women vitamin B-12 (50 μg) or placebo through 6 wk postpartum. All women were administered iron and folic acid supplements throughout pregnancy. One hundred eighty-three women were randomly assigned to receive vitamin B-12 and 183 to receive placebo. Compared with placebo recipients, vitamin B-12-supplemented women had significantly higher plasma vitamin B-12 concentrations at both the second (median vitamin B-12 concentration: 216 vs. 111 pmol/L, P vitamin B-12 concentration was 136 pmol/L in vitamin B-12-supplemented women vs. 87 pmol/L in the placebo group (P vitamin B-12-supplemented women, the incidence of delivering an infant with intrauterine growth retardation was 33 of 131 (25%) vs. 43 of 125 (34%) in those administered placebo (P = 0.11). In a subset of infants tested at 6 wk of age, median plasma vitamin B-12 concentration was 199 pmol/L in those born to supplemented women vs. 139 pmol/L in the placebo group (P = 0.01). Infant plasma methylmalonic acid and homocysteine concentrations were significantly lower in the vitamin B-12 group as well. Oral supplementation of urban Indian women with vitamin B-12 throughout pregnancy and early lactation significantly increases vitamin B-12 status of mothers and infants. It is important to determine whether there are correlations between these findings and neurologic and metabolic functions. This trial was registered at clinicaltrials.gov as NCT00641862.

  3. Drug delivery systems--2. Site-specific drug delivery utilizing monoclonal antibodies.

    Science.gov (United States)

    Ranade, V V

    1989-10-01

    Monoclonal antibodies (MAbs) are purified antibodies produced by a single clone of cells. They are engineered to recognize and bind to a single specific antigen. Accordingly, when administered, MAbs home in on a particular circulating protein or on cells that bear the correct antigenic signature on their surfaces. It is the specificity of MAbs that has made them valuable tools for health professions. Following the discovery of Kohler and Milstein regarding the method of somatic cell hybridization, a number of investigators have successfully adopted this technique to obtain T-lymphocyte hybrid cell lines by fusion of activated T (thymus derived) lymphocytes with a T lymphoma cell line leading to an immortalization of a specific differentiated function. The hybrids thus obtained were subsequently shown to produce homogeneous effector molecules with a wide variety of immune functions such as enhancement or suppression of antibody responses, generation of helper T cells, suppressor T cells and cytotoxic T cells. Study of these regulatory molecules has been further shown to provide a greater insight into the genetic, biochemical and molecular mechanisms responsible for cellular development, and the interaction and triggering of various cell types. The successful application of hybridoma technology has now resulted into several advances in the understanding the mechanism and treatment of diseases, especially cancer and development of vaccines, promotion of organ transplantation and therapy against parasites as well. Since monoclonal antibodies could be made in unlimited supply, they have been used in genetic studies such as mRNA and gene isolation, chromosomal isolation of specific genes, immunoglobulin structure, detection of new or rare immunoglobulin gene products, structural studies of enzymes and other proteins and structural and population studies of protein polymorphisms. In some instances, the monoclonal antibodies have been found to replace conventional antisera

  4. Polarized-neutron study of spin dynamics in the Kondo insulator YbB12.

    Science.gov (United States)

    Nemkovski, K S; Mignot, J-M; Alekseev, P A; Ivanov, A S; Nefeodova, E V; Rybina, A V; Regnault, L-P; Iga, F; Takabatake, T

    2007-09-28

    Inelastic neutron scattering experiments have been performed on the archetype compound YbB(12), using neutron polarization analysis to separate the magnetic signal from the phonon background. With decreasing temperature, components characteristic for a single-site spin-fluctuation dynamics are suppressed, giving place to specific, strongly Q-dependent, low-energy excitations near the spin-gap edge. This crossover is discussed in terms of a simple crystal-field description of the incoherent high-temperature state and a predominantly local mechanism for the formation of the low-temperature singlet ground state.

  5. Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection Against Ebolaviruses

    Science.gov (United States)

    2017-03-31

    search, analyzed data, and wrote and/or edited the paper . E.G. and L.M.W. designed the germline-reverted constructs and E.G., L.M.W., A.Z.W., D.M.A... albumin (PBSA), and incubated with dilutions of test antibody (5, 50 nM). Bound Abs were detected with anti-human IgG conjugated to horseradish

  6. Measurement of anti-IgA antibodies by a two-site immunoradiometric assay

    International Nuclear Information System (INIS)

    Homburger, H.A.; Smith, J.R.; Jacob, G.L.; Laschinger, C.; Naylor, D.H.; Pineda, A.A.

    1981-01-01

    To enable the detection of IgG class, anti-IgA antibodies and to investigate the possible occurrence of IgE class, anti-IgA antibodies, we developed a solid phase immunoradiometric assay, which uses purified IgA coupled covalently to microcrystalline cellulose as an immunosorbent. Radiolabeled, Fc specific anti-IgG and anti-IgE antibodies were used to detect specific aIgA after incubation of test sera or controls with the immunosorbent. IgG-aIgA were detected by the IRA in 100 and 67% of control sera with class specific and limited specificity aIgA. The IRA was sensitive to approximately two ng of class specific IgG-aIgA. IgG-aIgA also were detected by IRA in 7.9% of sera from patients with urticarial transfusion reactions and 73% of sera from patients with ataxia telangiectasia and IgA deficiency. Sera from 50 normal blood donors did not have detectable IgG-aIgA. Tests for IgE-aIgA were negative in all cases, including control sera with class specific IgG-aIgA. We conclude that the IRA is a sensitive and reproducible method for detection of class specific and limited specificity IgG-aIgA, and that IgE-aIgA do not mediate urticarial transfusion reactions

  7. Direct Detection of Protein Biomarkers in Human Fluids Using Site-Specific Antibody Immobilization Strategies

    Directory of Open Access Journals (Sweden)

    Maria Soler

    2014-01-01

    Full Text Available Design of an optimal surface biofunctionalization still remains an important challenge for the application of biosensors in clinical practice and therapeutic follow-up. Optical biosensors offer real-time monitoring and highly sensitive label-free analysis, along with great potential to be transferred to portable devices. When applied in direct immunoassays, their analytical features depend strongly on the antibody immobilization strategy. A strategy for correct immobilization of antibodies based on the use of ProLinker™ has been evaluated and optimized in terms of sensitivity, selectivity, stability and reproducibility. Special effort has been focused on avoiding antibody manipulation, preventing nonspecific adsorption and obtaining a robust biosurface with regeneration capabilities. ProLinker™-based approach has demonstrated to fulfill those crucial requirements and, in combination with PEG-derivative compounds, has shown encouraging results for direct detection in biological fluids, such as pure urine or diluted serum. Furthermore, we have implemented the ProLinker™ strategy to a novel nanoplasmonic-based biosensor resulting in promising advantages for its application in clinical and biomedical diagnosis.

  8. Direct detection of protein biomarkers in human fluids using site-specific antibody immobilization strategies.

    Science.gov (United States)

    Soler, Maria; Estevez, M-Carmen; Alvarez, Mar; Otte, Marinus A; Sepulveda, Borja; Lechuga, Laura M

    2014-01-29

    Design of an optimal surface biofunctionalization still remains an important challenge for the application of biosensors in clinical practice and therapeutic follow-up. Optical biosensors offer real-time monitoring and highly sensitive label-free analysis, along with great potential to be transferred to portable devices. When applied in direct immunoassays, their analytical features depend strongly on the antibody immobilization strategy. A strategy for correct immobilization of antibodies based on the use of ProLinker™ has been evaluated and optimized in terms of sensitivity, selectivity, stability and reproducibility. Special effort has been focused on avoiding antibody manipulation, preventing nonspecific adsorption and obtaining a robust biosurface with regeneration capabilities. ProLinker™-based approach has demonstrated to fulfill those crucial requirements and, in combination with PEG-derivative compounds, has shown encouraging results for direct detection in biological fluids, such as pure urine or diluted serum. Furthermore, we have implemented the ProLinker™ strategy to a novel nanoplasmonic-based biosensor resulting in promising advantages for its application in clinical and biomedical diagnosis.

  9. Synthesis, solution and crystal structure of the coenzyme B(12) analogue Co(β)-2'-fluoro-2',5'-dideoxyadenosylcobalamin.

    Science.gov (United States)

    Hunger, Miriam; Wurst, Klaus; Kräutler, Bernhard

    2015-07-01

    Crystal structure analyses have helped to decipher the mode of binding of coenzyme B12 (AdoCbl) in the active site of AdoCbl-dependent enzymes. However, the question of how such enzymes perform their radical reactions is still incompletely answered. A pioneering study by Gruber and Kratky of AdoCbl-dependent glutamate mutase (GLM) laid out a path for the movement of the catalytically active 5'-deoxyadenosyl radical, in which H-bonds between the protein and the 2'- and 3'-OH groups of the protein bound AdoCbl would play a decisive role. Studies with correspondingly modified coenzyme B12-analogues are of interest to gain insights into cofactor binding and enzyme mechanism. Here we report the preparation of Coβ-2'-fluoro-2',5'-dideoxyadenosylcobalamin (2'FAdoCbl), which lacks the 2'-OH group critical for the interaction in enzymes. 2'FAdoCbl was prepared by alkylation of cob(I)alamin, obtained from the electrochemical reduction of aquocobalamin. Spectroscopic data and a single crystal X-ray analysis of 2'FAdoCbl established its structure, which was very similar to that one of coenzyme B12. 2'FAdoCbl is a (19)F NMR active mimic of coenzyme B12 that may help to gain insights into binding interactions of coenzyme B12 with AdoCbl-dependent enzymes, proteins of B12 transport and of AdoCbl-biosynthesis, as well as with B12-riboswitches. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Metformin increases liver accumulation of vitamin B12 - An experimental study in rats

    DEFF Research Database (Denmark)

    Greibe, E; Miller, J W; Foutouhi, S H

    2013-01-01

    AIMS/HYPOTHESIS: Patients treated with metformin exhibit low levels of plasma vitamin B(12) (B(12)), and are considered at risk for developing B(12) deficiency. In this study, we investigated the effect of metformin treatment on B(12) uptake and distribution in rats. METHODS: Sprague Dawley rats (n...... that metformin has no decreasing effect on the B(12) absorption. CONCLUSIONS/INTERPRETATION: These results show that metformin treatment increases liver accumulation of B(12), thereby resulting in decreases in circulating B(12) and kidney accumulation of the vitamin. Our data questions whether the low plasma B......(12) observed in patients treated with metformin reflects impaired B(12) status, and rather suggests altered tissue distribution and metabolism of the vitamin....

  11. Multivalent peptidic linker enables identification of preferred sites of conjugation for a potent thialanstatin antibody drug conjugate.

    Directory of Open Access Journals (Sweden)

    Sujiet Puthenveetil

    Full Text Available Antibody drug conjugates (ADCs are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads beyond the mictotubule inhibitors and DNA damaging agents has led us to the recent discovery of an mRNA splicing inhibitor, thailanstatin, as a potent ADC payload. In our previous work, we observed that the potency of this payload was uniquely tied to the method of conjugation, with lysine conjugates showing much superior potency as compared to cysteine conjugates. However, the ADC field is rapidly shifting towards site-specific ADCs due to their advantages in manufacturability, characterization and safety. In this work we report the identification of a highly efficacious site-specific thailanstatin ADC. The site of conjugation played a critical role on both the in vitro and in vivo potency of these ADCs. During the course of this study, we developed a novel methodology of loading a single site with multiple payloads using an in situ generated multi-drug carrying peptidic linker that allowed us to rapidly screen for optimal conjugation sites. Using this methodology, we were able to identify a double-cysteine mutant ADC delivering four-loaded thailanstatin that was very efficacious in a gastric cancer xenograft model at 3mg/kg and was also shown to be efficacious against T-DM1 resistant and MDR1 overexpressing tumor cell lines.

  12. Multivalent peptidic linker enables identification of preferred sites of conjugation for a potent thialanstatin antibody drug conjugate.

    Science.gov (United States)

    Puthenveetil, Sujiet; He, Haiyin; Loganzo, Frank; Musto, Sylvia; Teske, Jesse; Green, Michael; Tan, Xingzhi; Hosselet, Christine; Lucas, Judy; Tumey, L Nathan; Sapra, Puja; Subramanyam, Chakrapani; O'Donnell, Christopher J; Graziani, Edmund I

    2017-01-01

    Antibody drug conjugates (ADCs) are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads beyond the mictotubule inhibitors and DNA damaging agents has led us to the recent discovery of an mRNA splicing inhibitor, thailanstatin, as a potent ADC payload. In our previous work, we observed that the potency of this payload was uniquely tied to the method of conjugation, with lysine conjugates showing much superior potency as compared to cysteine conjugates. However, the ADC field is rapidly shifting towards site-specific ADCs due to their advantages in manufacturability, characterization and safety. In this work we report the identification of a highly efficacious site-specific thailanstatin ADC. The site of conjugation played a critical role on both the in vitro and in vivo potency of these ADCs. During the course of this study, we developed a novel methodology of loading a single site with multiple payloads using an in situ generated multi-drug carrying peptidic linker that allowed us to rapidly screen for optimal conjugation sites. Using this methodology, we were able to identify a double-cysteine mutant ADC delivering four-loaded thailanstatin that was very efficacious in a gastric cancer xenograft model at 3mg/kg and was also shown to be efficacious against T-DM1 resistant and MDR1 overexpressing tumor cell lines.

  13. Vitamin B12 transport from food to the body's cells--a sophisticated, multistep pathway

    DEFF Research Database (Denmark)

    Nielsen, Marianne J; Rasmussen, Mie R; Andersen, Christian B F

    2012-01-01

    Vitamin B(12) (B(12); also known as cobalamin) is a cofactor in many metabolic processes; deficiency of this vitamin is associated with megaloblastic anaemia and various neurological disorders. In contrast to many prokaryotes, humans and other mammals are unable to synthesize B(12). Instead...... in the transport pathway are also known culprits of functional B(12) deficiency. Biochemical and genetic approaches have identified novel proteins in the B(12) transport pathway--now known to involve more than 15 gene products--delineating a coherent pathway for B(12) trafficking from food to the body's cells...

  14. Simultaneous radioassay of serum vitamin B12 and folic acid

    International Nuclear Information System (INIS)

    Gutcho, S.; Mansbach, L.

    1977-01-01

    The radioassays of vitamin B 12 and folic acid can be carried out in a single tube to give the simultaneous assay of both vitamins in 100 μl of serum. Release of bound vitamins from their endogenous binders and the destruction of these binders are effected by a heating step at pH 9.3. The subsequent binding reactions with hog intrinsic factor and milk binder protein proceed advantageously and simultaneously in the same tube at pH 9.3. A single set of dual reagents replaces two sets of reagents that would normally be used for separate radioassays. Complete separation of bound radioactivities, [ 57 Co] cyanocobalamin and 125 I-labeled folate derivative, is obtained in a dual-channel gamma counter with no requirement for any correction for spill-over of counting data. Analytical results are comparable to those found for previously developed individual radioassays. The simultaneous assay has decreased technical time of analysis for these interrelated vitamins by about 50%

  15. Monoclonal antibodies that bind the renal Na+/glucose symport system. 1. Identification

    International Nuclear Information System (INIS)

    Wu, J.S.R.; Lever, J.E.

    1987-01-01

    Phlorizin is a specific, high-affinity ligand that binds the active site of the Na + /glucose symporter by a Na + -dependent mechanism but is not itself transported across the membrane. The authors have isolated a panel of monoclonal antibodies that influence high-affinity, Na + -dependent phlorizin binding to pig renal brush border membranes. Antibodies were derived after immunization of mice either with highly purified renal brush border membranes or with apical membranes purified from LLC-PK 1 , a cell line of pig renal proximal tubule origin. Antibody 11A3D6, an IgG/sub 2b/, reproducibly stimulated Na + -dependent phlorizin binding whereas antibody 18H10B12, an IgM, strongly inhibited specific binding. These effects were maximal after 30-min incubation and exhibited saturation at increased antibody concentrations. Antibodies did not affect Na + -dependent sugar uptake in vesicles but significantly prevented transport inhibition by bound phlorizin. Antibodies recognized a 75-kDa antigen identified by Western blot analysis of brush border membranes, and a 75-kDa membrane protein could be immunoprecipitated by 18H10B12. These properties, provide compelling evidence that the 75-kDa antigen recognized by these antibodies is a component of the renal Na + /glucose symporter

  16. Determination of four forms of vitamin B12 and other B vitamins in seawater by liquid chromatography/tandem mass spectrometry.

    Science.gov (United States)

    Heal, Katherine R; Carlson, Laura Truxal; Devol, Allan H; Armbrust, E Virginia; Moffett, James W; Stahl, David A; Ingalls, Anitra E

    2014-11-30

    Vitamin B(12) is an essential nutrient for more than half of surveyed marine algae species, but methods for directly measuring this important cofactor in seawater are limited. Current mass spectrometry methods do not quantify all forms of B(12), potentially missing a significant portion of the B(12) pool. We present a method to measure vitamins B(1), B(2), B(6), B(7) and four forms of B(12) dissolved in seawater. The method entails solid-phase extraction, separation by ultra-performance liquid chromatography, and detection by triple-quadrupole tandem mass spectrometry using stable-isotope-labeled internal standards. We demonstrated the use of this method in the environment by analyzing B(12) concentrations at different depths in the Hood Canal, part of the Puget Sound estuarine system in Washington State. Recovery of vitamin B(12) forms during the preconcentration steps was >71% and the limits of detection were B(12) in seawater at our field site. We developed a method for quantifying four forms of B(12) in seawater by liquid chromatography/mass spectrometry with the option of simultaneous analysis of vitamins B(1), B(2), B(6), and B(7). We validated the method and demonstrated its application in the field. Copyright © 2014 John Wiley & Sons, Ltd.

  17. Conserved epitope on several human vitamin K-dependent proteins: location of the antigenic site and influence of metal ions on antibody binding

    International Nuclear Information System (INIS)

    Church, W.R.; Messier, T.; Howard, P.R.; Amiral, J.; Meyer, D.; Mann, K.G.

    1988-01-01

    A murine monoclonal antibody (designated H-11) produced by injecting mice with purified human protein C was found to bind several human vitamin K-dependent proteins. Using a solid-phase competitive radioimmunoassay with antibody immobilized onto microtiter plates, binding of 125 I-labeled protein C to the antibody was inhibited by increasing amounts of protein C, prothrombin, and Factors X and VII over a concentration range of 1 x 10 -8 to 1 x 10 -6 M. Chemical treatment of prothrombin with a variety of agents did not destroy the antigenic site recognized by the antibody as measured by immunoblotting of prothrombin or prothrombin derivative immobilized onto nitrocellulose. Immunoblotting of purified vitamin K-dependent polypeptides with the monoclonal antibody following sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrophoretic transfer to nitrocellulose indicated that the antigenic site was found on the light chains of protein C and Factor X. The exact location of the antigenic determinant for antibody H-11 was established using synthetic peptides. Comparison of protein sequences of bovine and human vitamin K-dependent proteins suggests that the sequence Phe-Leu-Glu-Glu-Xaa-Arg/Lys is required for antibody binding. Increasing concentrations of Ca 2+ , Mg 2+ , or Mn 2+ partially inhibited binding of 125 I-protein C to the antibody in a solid-phase assay system with half-maximal binding observed at divalent metal ion concentrations of 2, 4, and 0.6 mM, respectively. The antigenic site thus recognized by monoclonal antibody H-11 is located at the amino-terminal region in the highly conserved γ-carboxyglutamic acid-containing domains of several, but not all, vitamin K-dependent proteins

  18. Enhanced tumor retention of a radiohalogen label for site-specific modification of antibodies.

    Science.gov (United States)

    Boswell, C Andrew; Marik, Jan; Elowson, Michael J; Reyes, Noe A; Ulufatu, Sheila; Bumbaca, Daniela; Yip, Victor; Mundo, Eduardo E; Majidy, Nicholas; Van Hoy, Marjie; Goriparthi, Saritha N; Trias, Anthony; Gill, Herman S; Williams, Simon P; Junutula, Jagath R; Fielder, Paul J; Khawli, Leslie A

    2013-12-12

    A known limitation of iodine radionuclides for labeling and biological tracking of receptor targeted proteins is the tendency of iodotyrosine to rapidly diffuse from cells following endocytosis and lysosomal degradation. In contrast, radiometal-chelate complexes such as indium-111-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (In-111-DOTA) accumulate within target cells due to the residualizing properties of the polar, charged metal-chelate-amino acid adduct. Iodine radionuclides boast a diversity of nuclear properties and chemical means for incorporation, prompting efforts to covalently link radioiodine with residualizing molecules. Herein, we describe the Ugi-assisted synthesis of [I-125]HIP-DOTA, a 4-hydroxy-3-iodophenyl (HIP) derivative of DOTA, and demonstration of its residualizing properties in a murine xenograft model. Overall, this study displays the power of multicomponent synthesis to yield a versatile radioactive probe for antibodies across multiple therapeutic areas with potential applications in both preclinical biodistribution studies and clinical radioimmunotherapies.

  19. Vitamin B12 deficiency presenting as an acute confusional state: a ...

    African Journals Online (AJOL)

    EB

    2013-09-03

    Sep 3, 2013 ... occurred following parenteral vitamin B12 replacement therapy. Conclusion: This case report highlights one of the neuro-psychiatric presentations of vitamin B12 deficiency .... and Occupational Health Abstract No:.

  20. Evaluation of serum Vitamin B12 level and related nutritional status ...

    African Journals Online (AJOL)

    2016-03-29

    Mar 29, 2016 ... This study was aimed to investigate the association between serum. Vitamin B12 ... Consumption of certain types of food contributes to increase vitB12 level. Key words: ... nutritional status among apparently healthy obese.

  1. Genetic determinants of serum vitamin B12 and their relation to body mass index

    DEFF Research Database (Denmark)

    Allin, Kristine H.; Friedrich, Nele; Pietzner, Maik

    2017-01-01

    for associations between (1) serum vitamin B12 levels and body mass index (BMI), (2) genetic variants and serum vitamin B12 levels, and (3) genetic variants and BMI. The effect of a genetically determined decrease in serum vitamin B12 on BMI was estimated by instrumental variable regression. Decreased serum......Lower serum vitamin B12 levels have been related to adverse metabolic health profiles, including adiposity. We used a Mendelian randomization design to test whether this relation might be causal. We included two Danish population-based studies (ntotal = 9311). Linear regression was used to test...... vitamin B12 associated with increased BMI (P vitamin B12 associated variants associated strongly with serum vitamin B12 (P vitamin B12...

  2. vitamin b12 levels in patients with type 2 diabetes mellitus

    African Journals Online (AJOL)

    is involved in DNA synthesis, fatty acid metabolism. VITAMIN B12 ..... concentrations of homocysteine, folate and vitamin B12 in ... and folic acid: a cross-sectional study in patients with type 2 ... pregnant women with polycystic ovary syndrome.

  3. Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site

    Energy Technology Data Exchange (ETDEWEB)

    Wibmer, Constantinos Kurt; Gorman, Jason; Anthony, Colin S.; Mkhize, Nonhlanhla N.; Druz, Aliaksandr; York, Talita; Schmidt, Stephen D.; Labuschagne, Phillip; Louder, Mark K.; Bailer, Robert T.; Karim, Salim S. Abdool; Mascola, John R.; Williamson, Carolyn; Moore, Penny L.; Kwong, Peter D.; Morris, Lynn (NHLS-South Africa); (NIH); (Witwatersrand); (KwaZulu-Natal)

    2016-08-31

    ABSTRACT

    All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report the isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycan-dependent CD4 binding site B-cell lineage.

    IMPORTANCEThe conserved CD4 binding site on gp120 is a major target for HIV-1 vaccine design, but key events in the elicitation and maturation of

  4. 4-ethylphenyl-cobalamin impairs tissue uptake of vitamin B12 and causes vitamin B12 deficiency in mice

    DEFF Research Database (Denmark)

    Mutti, Elena; Ruetz, Markus; Birn, Henrik

    2013-01-01

    Coβ-4-ethylphenyl-cob(III) alamin (EtPhCbl) is an organometallic analogue of vitamin B12 (CNCbl) which binds to transcobalamin (TC), a plasma protein that facilitates the cellular uptake of cobalamin (Cbl). In vitro assays with key enzymes do not convert EtPhCbl to the active coenzyme forms of Cbl...... treated with EtPhCbl (1.01±0.12 µmol/L) compared to controls (0.30±0.02 µmol/L) and CNCbl (0.29±0.01 µmol/L) treated animals. The same pattern was observed for tHcy. Plasma total Cbl concentration was higher in animals treated with EtPhCbl (128.82±1.87 nmol/L) than in CNCbl treated animals (87.......64±0.93 nmol/L). However, the organ levels of total Cbl were significantly lower in animals treated with EtPhCbl compared to CNCbl treated animals or controls, notably in the liver (157.07±8.56 pmol/g vs. 603.85±20.02 pmol/g, and 443.09±12.32 pmol/g, respectively). Differences between the three groups...

  5. The distribution of total vitamin b12 holotranscobalamin and the active vitamin b12 fraction in the first 5 weeks postpartum

    NARCIS (Netherlands)

    van der Woude, D.A.A.; Pijnenborg, J.M.A.; de Vries, J.; van Wijk, E.M.

    2018-01-01

    Introduction Total vitamin B12 levels decrease significantly during pregnancy and recover to normal values within 8-week postpartum. Holotranscobalamin (holoTC) reflects the active part of vitamin B12 and has been shown to remain constant during pregnancy and postpartum. A mechanism of

  6. Vitamin B-12 supplementation of rural Mexican women changes biochemical B-12 status indicators but does not affect hematology or a bone turnover marker

    Science.gov (United States)

    Based on the high prevalence of low serum vitamin B-12 concentrations and low dietary intake of the vitamin in Latin American studies including research in Mexico, it appears that vitamin B-12 deficiency is common. Whether this is associated with adverse effects on human function is unknown. To eval...

  7. Assessment of Serum Vitamin B12 Concentrations in Patients with a ...

    African Journals Online (AJOL)

    Serum vitamin B12 levels were obtained preoperatively and every 6 months postoperatively. All patients received 100 microgram of vitamin B-12 twice yearly. Follow up ranged from 3-10 years. Results All 16 patients included in the study had a normal concentration of serum vitamin B12 preoperatively with a range of ...

  8. Prevalence of Vitamin B12 deficiency in patients of type 2 diabetes ...

    African Journals Online (AJOL)

    Conclusion: Our study demonstrated significantly high prevalence of vitamin B12 deficiency in patients treated with metformin with significant effect of dose and duration of metformin use on B12 levels. Physicians must recognize this important fact and screen diabetics on metformin therapy for underlying B12 deficiency.

  9. Solid-phase radioimmunoassay for vitamin B12 in serum, with use of radioiodinated tyrosine methyl ester of vitamin B12

    International Nuclear Information System (INIS)

    Endres, D.B.; Painter, K.; Niswender, G.D.

    1978-01-01

    Although radioassays for vitamin B 12 with use of any of several binding proteins have been available for many years, a radioimmunoassay for B 12 has not been reported. We describe here such a radioimmunoassay, incorporating, for the first time, a radioiodinated tyrosine methyl ester of B 12 as the radioactive tracer. Polypropylene tubes are coated with antiserum raised in a rabbit against B 12 /bovine serum albumin to simplify the separation of bound and free radioactivity. Factors affecting the preparation of coated tubes are described. The assay is accurate, sensitive, precise, and specific for vitamin B 12 . Accuracy of the assay is unaffected by the presence of denatured protein. The advantages of this radioimmunoassay over conventional radioassays are discussed

  10. Two-site sandwich immunoradiometric assay of human lymphotoxin with monoclonal antibodies and its applications

    Energy Technology Data Exchange (ETDEWEB)

    Meager, A; Parti, S; Leung, H; Woolley, J; Peil, E; Sidhu, S; Roberts, T

    1987-11-23

    Three monoclonal antibodies (MoAbs L49-15, L81-11 and L238-14) were raised against recombinant human lymphotoxin (rLT) derived from E. coli containing the cDNA sequence specifying LT. These MoAbs were ideal reagents for immunoassay of LT and a very sensitive, highly specific immunoradiometric assay (IRMA) was developed. This assay was rapid to perform and was capable of detecting as little as 10 pg/ml of LT. Application of the LT IRMA in combination with previously developed human gamma-interferon (IFN-..gamma..) and human tumour necrosis factor (TNF)-specific IRMA permitted independent estimations of these three substances to be carried out in parallel. By these means, it was found that RPMI 1788 lymphoblastoid cell line produced both LT and TNF, but not IFN-..gamma... Extensive analyses on cytokine (monokine and lymphokine) preparations derived from a variety of activated lymphocytes are also reported. Co-production of LT, TNF, and IFN-..gamma.. was a common finding, even occurring in alloantigen-specific T helper cell clones. 45 refs.; 3 figs.; 4 tabs.

  11. Vitamin B 12 absorption: correction of intestinal retention by whole-body profile activity of vitamin B 12-58 cobalt and by double tracer technique

    International Nuclear Information System (INIS)

    Goncalves, M.R. Bencke; Gheldof, R.; Paternot, L. van Tricht; Delmotte, E.; Verschaeren, A.; Martin, P.; Verhas, M.; Universidade Federal, Rio de Janeiro, RJ

    1997-01-01

    Full text. Intestinal retention could give false negative results in determining the whole-body retention of vitamin B 12 absorption (WBC B12-58Co). After having validate the WBC B12-58Co, taking the Schilling test as reference, we have studied the feasibility to evaluate the intestinal contamination by measurement of the profile activity distribution of vitamin B12-58Co and by a double tracer technique (WBC B12-58Co/ WBC 51 Cr Cl3). Methodology: twenty five patients were studied for the setting up of the new methodology. For eleven of them the WBC B12-58 Co retention was measured at the 7th day after the oral administration of 37KBq of B12-58Co using a four detectors whole body counter. One week later, a Schilling test was performed after the oral absorption of 18,5 KBq B12-57Co. Results were expressed as %ID. In these patients, one single peak of hepatic activity was observed on the whole body profile and thus no further intestinal correction was needed. In order to evaluate the intestinal contribution, we made in nine other patients the profile of the whole body distribution of activity at 1 h, 1 week and two weeks after the oral administration of B12-58Co. For five other patients a double tracer technique was used for intestinal correction after the simultaneous oral administration of 37 KBq of B12-58Co and 1,85 MBq of 51 Cr Cl3. The B12-58Co absorption was evaluated after intestinal correction based on subtraction of the 51Cr Cl3 contribution after the formula: B12-58Co(%ID) = WBC B12-58Co - WBC 51 Cr Cl3/1 - WBC 51 Cr Cl3. Results: the correlation with the Schilling test was found excellent: r=0,94 (n=11). The normality for WBC retention (n=7) was define as 53,2 +-12,4% ID (SD). For nine patients studied at the 7th day, the presence of a double peak (hepatic and intestinal peaks) allowed the subtraction by exponential extrapolation; the correction range was 4,4% to 37,2%. With the exception of one observation there was no difference in the measure of vitamin

  12. Clinical value of serum vitamin B12 and folate in cerebrovascular disease

    International Nuclear Information System (INIS)

    Zhan Hao; Zhang Yongxue

    2002-01-01

    To study the clinical value of serum vitamin B 12 and folate in cerebrovascular disease, the concentration of serum vitamin B 12 and folate in 32 patients with cerebrovascular disease was measured by radioimmunoassay. The results showed that the changes in folate in all groups were not significant. The content of vitamin B 12 in multi-infarct dementia was markedly lower than that in cerebral infarction and cerebral hemorrhage. Moreover, the level of vitamin B 12 was lower in paralytic patients with muscular strength of grade 0-III. It can be concluded that serum vitamin B 12 level had association with intelligent disorder and paralytic degree

  13. Binding of the mannose-specific lectin, griffithsin, to HIV-1 gp120 exposes the CD4-binding site

    CSIR Research Space (South Africa)

    Alexandre, Kabamba B

    2011-09-01

    Full Text Available of the lectin griffithsin (GRFT) with HIV-1 gp120 and its effects on exposure of the CD4-binding site (CD4bs). We found that GRFT enhanced the binding of HIV-1 onto plates coated with anti-CD4bs antibodies b12, b6 or the CD4 receptor mimetic, CD4-IgG2...

  14. Vitamin B12 status and the effects of vitamin B12 supplementation during the first year of life of spring calves from pasture-fed dairy herds.

    Science.gov (United States)

    Grace, N D; Knowles, S O; Nortjé, R

    2014-09-01

    To determine the vitamin B12 status of dairy calves during their first year of life, and to evaluate the benefits of vitamin B12 supplementation. In Experiment I, 20 17-day-old heifer calves from the AgResearch Flock House herd were monitored until 198 days old. On Days 0 and 90 of the study, half of the animals received an injection of microencapsulated vitamin B12 at 0.12 mg/kg bodyweight. All received colostrum, milk replacer and calf meal, with ad libitum access to pasture. At regular intervals the calves were weighed and serum collected for vitamin B12 measurement. In Experiment II at Flock House and the adjacent Landcorp Tangimoana station, 80 150-day-old heifer calves were monitored until 342 days old. On Days 0 and 97, half of the animals received vitamin B12 as per Experiment I. At regular intervals samples were collected from 12 calves per group, to determine concentrations of vitamin B12 in serum. Mean concentration of vitamin B12 in milk replacer was 63 (SE 4) µg/kg dry matter (DM). Cobalt concentrations in calf meal were 0.45-1.58 and 0.07-0.28 mg/kg DM in pastures. From 17 to 198 days of age (Experiment I) mean concentrations of vitamin B12 in serum of the control group decreased from 119 (SE 8) to 57 (SE 5) pmol/L. From 150 to 342 days of age (Experiment II), overall mean concentrations of the control groups at Flock House and Tangimoana were 90 (SE 2) and 96 (SE 3) pmol/L, respectively. Vitamin B12 injections increased (ppasture-based diet. Supplementation increased concentrations of vitamin B12 in serum but did not improve liveweight gains. Under this calf rearing system, vitamin B12 deficiency is unlikely to occur prior to weaning, and vitamin B12 supplementation is unlikely to increase growth rates of grazing calves when concentrations of vitamin B12 in serum are > 90 pmol/L.

  15. Electronic properties and bulk moduli of novel boron nitride polymorphs: hyperdiamond B12N12 and the simple cubic B24N24, B12N12 fulborenites

    International Nuclear Information System (INIS)

    Pokrivnyj, V.V.; Bekenev, V.L.

    2006-01-01

    Equation of states, energy band structure, electronic density of states, and bulk moduli of the boron nitride fulborenite crystals: B 12 N 12 with a diamond lattice and B 24 N 24 , B 12 N 12 with a simple cubic lattice have been calculated for the first time by FLAPW method. Calculated parameters of these compounds are as follows: equilibrium lattice parameter, the length of B-N bond, the number of atoms per conventional cell, density, bulk modulus, band gap. Hyperdiamond B 12 N 12 is shown to have the record bulk modulus B 0 = 658 GPa [ru

  16. Folato, vitamina B12 e ferritina sérica e defeitos do tubo neural Folate, vitamin B12, serum ferritin and defects of the neural tube

    Directory of Open Access Journals (Sweden)

    Gizele Thame

    1998-09-01

    Full Text Available Objetivo: verificar os níveis de folatos, vitamina B12 e ferritina em pacientes cujos fetos apresentaram defeitos de tubo neural (DTN. O folato sangüíneo e a vitamina B12 atuam como cofatores para as enzimas envolvidas na biossíntese do DNA. A interrupção deste processo pode impedir o fechamento do tubo neural. A suplementação vitamínica contendo folato pode reduzir as taxas de ocorrência de defeitos de tubo neural, embora exista a preocupação de que esta prevenção possa mascarar a deficiência de vitamina B12. Métodos: dosagens de vitamina B12 e ferritina pelo método de enzimaimunoensaio com micropartículas e a dosagens de ácido fólico pelo método de captura iônica (IMx ABBOTT. Resultados: a porcentagem de gestantes com deficiência de vitamina B12 (níveis séricos Purpose: to determine folate, vitamin B12 and ferritin levels in patients whose fetuses presented neural-tube defects (NTD. Blood folate and vitamin B12 act as cofactors of enzymes involved in DNA biosynthesis. Interruption of this process may block neural-tube closing. Vitamin supplementation with folate may reduce occurrence rates and recurrence of NTD, although there is concern about the fact that this prevention may mask vitamin B12 deficiency. Methods: vitamin B12 and ferritin determinations by enzyme immunoassay with microparticles and folic acid determination using the ion capture method (IMx ABBOTT. Results: the percentage of pregnant women with vitamin B12 deficirncy (serum levels < 150 pg/ml was 11.8%. There was no case of folate deficiency (serum levels < 3.0 ng/ml and prevalence of pregnant women with iron store deficiency was 47.1% (serum levels < ng/mg. Conclusions: occording to the results obtained in this study (prevalence of 11.8% of vitamin B12 and 0% of folate deficient pregnant women we suggest that supplementation should be administered after serum vitamin B12 determination.

  17. Vitamin B12 supplementation during pregnancy and postpartum improves B12 status of both mothers and infants but vaccine response in mothers only: a randomized clinical trial in Bangladesh

    Science.gov (United States)

    Purpose Poor vitamin B12 (B12) status is associated with adverse outcomes in pregnancy and infancy. Little is known about effects of B12 supplementation on immune function. The present study aimed to evaluate effects of pre- and postnatal B12 supplementation on biomarkers of B12 status and vaccine-s...

  18. A Camelid-derived Antibody Fragment Targeting the Active Site of a Serine Protease Balances between Inhibitor and Substrate Behavior.

    Science.gov (United States)

    Kromann-Hansen, Tobias; Oldenburg, Emil; Yung, Kristen Wing Yu; Ghassabeh, Gholamreza H; Muyldermans, Serge; Declerck, Paul J; Huang, Mingdong; Andreasen, Peter A; Ngo, Jacky Chi Ki

    2016-07-15

    A peptide segment that binds the active site of a serine protease in a substrate-like manner may behave like an inhibitor or a substrate. However, there is sparse information on which factors determine the behavior a particular peptide segment will exhibit. Here, we describe the first x-ray crystal structure of a nanobody in complex with a serine protease. The nanobody displays a new type of interaction between an antibody and a serine protease as it inserts its complementary determining region-H3 loop into the active site of the protease in a substrate-like manner. The unique binding mechanism causes the nanobody to behave as a strong inhibitor as well as a poor substrate. Intriguingly, its substrate behavior is incomplete, as 30-40% of the nanobody remained intact and inhibitory after prolonged incubation with the protease. Biochemical analysis reveals that an intra-loop interaction network within the complementary determining region-H3 of the nanobody balances its inhibitor versus substrate behavior. Collectively, our results unveil molecular factors, which may be a general mechanism to determine the substrate versus inhibitor behavior of other protease inhibitors. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. A Camelid-derived Antibody Fragment Targeting the Active Site of a Serine Protease Balances between Inhibitor and Substrate Behavior*

    Science.gov (United States)

    Kromann-Hansen, Tobias; Oldenburg, Emil; Yung, Kristen Wing Yu; Ghassabeh, Gholamreza H.; Muyldermans, Serge; Declerck, Paul J.; Huang, Mingdong; Andreasen, Peter A.; Ngo, Jacky Chi Ki

    2016-01-01

    A peptide segment that binds the active site of a serine protease in a substrate-like manner may behave like an inhibitor or a substrate. However, there is sparse information on which factors determine the behavior a particular peptide segment will exhibit. Here, we describe the first x-ray crystal structure of a nanobody in complex with a serine protease. The nanobody displays a new type of interaction between an antibody and a serine protease as it inserts its complementary determining region-H3 loop into the active site of the protease in a substrate-like manner. The unique binding mechanism causes the nanobody to behave as a strong inhibitor as well as a poor substrate. Intriguingly, its substrate behavior is incomplete, as 30–40% of the nanobody remained intact and inhibitory after prolonged incubation with the protease. Biochemical analysis reveals that an intra-loop interaction network within the complementary determining region-H3 of the nanobody balances its inhibitor versus substrate behavior. Collectively, our results unveil molecular factors, which may be a general mechanism to determine the substrate versus inhibitor behavior of other protease inhibitors. PMID:27226628

  20. Acquired thermotolerance and heat shock in the extremely thermophilic archaebacterium Sulfolobus sp. strain B12.

    Science.gov (United States)

    Trent, J D; Osipiuk, J; Pinkau, T

    1990-03-01

    The extreme thermophile Sulfolobus sp. strain B12 exhibits an acquired thermotolerance response. Thus, survival of cells from a 70 degrees C culture at the lethal temperature of 92 degrees C was enhanced by as much as 6 orders of magnitude over a 2-h period if the culture was preheated to 88 degrees C for 60 min or longer before being exposed to the lethal temperature. In eubacteria and eucaryotes, acquired thermotolerance correlates with the induced synthesis of a dozen or so proteins known as heat shock proteins. In this Sulfolobus species, it correlates with the preferential synthesis of primarily one major protein (55 kilodaltons) and, to a much lesser extent, two minor proteins (28 and 35 kilodaltons). Since the synthesis of all other proteins was radically reduced and these proteins were apparently not degraded or exported, their relative abundance within the cell increased during the time the cells were becoming thermotolerant. They could not yet be related to known heat shock proteins. In immunoassays, they were not cross-reactive with antibodies against heat shock proteins from Escherichia coli (DnaK and GroE), which are highly conserved between eubacteria and eucaryotes. However, it appears that if acquired thermotolerance depends on the synthesis of protective proteins, then in this extremely thermophilic archaebacterium it depends primarily on one protein.

  1. Electronic properties and bulk moduli of new boron nitride polymorphs, i.e., hyperdiamond B12N12 and simple cubic B24N24, B12N12 fulborenites

    International Nuclear Information System (INIS)

    Pokropivny, V. V.; Bekenev, V. L.

    2006-01-01

    The energy-band structure, density of states, electron density distribution, equation of state, and bulk moduli of three boron-nitride fulborenite crystals, i.e., B 12 N 12 with diamond lattice and B 24 N 24 , B 12 N 12 with simple cubic lattice, whose sites contain fulborene B 12 N 12 and B 24 N 24 molecules, are calculated for the first time using the full-potential linearized augmented plane wave method. The following hyperdiamond B 12 N 12 parameters were obtained: the equilibrium lattice parameter a = 1.1191 nm, the B-N bond length a BN = 0.1405 nm, the number of atoms per unit cell Z = 192, the density ρ = 2.823 g/cm 3 , the bulk modulus B 0 = 658 GPa, and the band gap ΔE g = 3.05 eV. This is a previously unknown unique light superhard semiconductor faujasite with a recorded bulk modulus higher than that of diamond. There are reasons to assume that it is a E phase. The characteristics of B 24 N 24 with simple cubic lattice are as follows: the equilibrium lattice parameter a = 0.7346 nm, the B-N bond length a BN = 0.1521 nm, the number of atoms per unit cell Z = 48, the density ρ = 2.495 g/cm 3 , the bulk modulus B 0 = 367 GPa, and the band gap ΔE g = 3.76 eV. This material is a heteropolar semiconductor or insulator with a bulk modulus comparable with that of cubic boron nitride, as well as a new boron-nitride zeolite with channel diameter of 0.46 nm. B 12 N 12 with simple cubic lattice is a molecular semimetal

  2. High prevalence of human anti-bovine IgG antibodies as the major cause of false positive reactions in two-site immunoassays based on monoclonal antibodies

    DEFF Research Database (Denmark)

    Andersen, Ditte C; Koch, Claus; Jensen, Charlotte H

    2004-01-01

    were purified by protein G affinity chromatography from culture supernatant containing 10% (v/v) fetal calf serum (FCS). Human anti-animal IgG (bovine, mouse, horse, and swine) antibodies and human anti-bovine serum albumin antibodies were measured using an ELISA design, with direct bridging...... of the solid phase and biotinylated antigens. The false positive reactions were abolished by addition of 1% (v/v) bovine serum to the dilution buffer (DB). Human anti-bovine IgG antibodies (HABIA) were detected in 99 out of 104 sera from blood donors (50 females; 54 males). HABIA levels in male sera (n = 54......) were positively correlated to the false positive signals in the PP14 ELISA (r = 0.923; p detected in the donor sera, but levels and frequencies were lower compared to that of HABIA. Furthermore, HABIA were...

  3. Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis.

    Science.gov (United States)

    Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

    2018-03-28

    To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori ( H. pylori ) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve ( R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12

  4. Genetic Variation in Vitamin B-12 Content of Bovine Milk and Its Association with SNP along the Bovine Genome

    NARCIS (Netherlands)

    Rutten, M.J.M.; Bouwman, A.C.; Sprong, R.C.; Arendonk, van J.A.M.; Visker, M.H.P.W.

    2013-01-01

    Vitamin B-12 (also called cobalamin) is essential for human health and current intake levels of vitamin B-12 are considered to be too low. Natural enrichment of the vitamin B-12 content in milk, an important dietary source of vitamin B-12, may help to increase vitamin B-12 intake. Natural enrichment

  5. Genetic disorders of vitamin B12 metabolism: eight complementation groups – eight genes

    Science.gov (United States)

    Froese, D. Sean; Gravel, Roy A.

    2010-01-01

    Vitamin B12 (cobalamin, Cbl) is an essential nutrient in human metabolism. Genetic diseases of vitamin B12 utilisation constitute an important fraction of inherited newborn disease. Functionally, B12 is the cofactor for methionine synthase and methylmalonyl CoA mutase. To function as a cofactor, B12 must be metabolised through a complex pathway that modifies its structure and takes it through subcellular compartments of the cell. Through the study of inherited disorders of vitamin B12 utilisation, the genes for eight complementation groups have been identified, leading to the determination of the general structure of vitamin B12 processing and providing methods for carrier testing, prenatal diagnosis and approaches to treatment. PMID:21114891

  6. Interaction of conjugated bile acids and detergents with a radiosorbent assay of vitamin B-12

    International Nuclear Information System (INIS)

    Andersen, K.-J.; Romslo, I.

    1977-01-01

    The effect of conjugated bile acids and detergents on the radiosorbent technique for the determination of vitamin B-12 activity is reported. It is shown that whereas the non-ionic detergent Triton X-100 has no effect on the vitamin B-12-radiosorbent assay, the addition of ionic detergents, e.g. glycocholic acid, taurocholic acid or sodium lauryl sulfate, results in a falsely-elevated vitamin B-12 activity presumably due to the disruption of the binding of vitamin B-12 to the intrinsic factor-Sephadex complex. This effect may be of importance not only to the radiosorbent assaying of vitamin B-12, but to the in vivo intestinal absorption of vitamin B-12 as well

  7. Purification of rat intestinal receptor for intrinsic factor-vitamin B12 complex

    International Nuclear Information System (INIS)

    Yamada, Shoji; Itaya, Harutaka; Nakazawa, Osamu; Fukuda, Morimichi.

    1977-01-01

    The intrinsic factor (IF) in a rat gastric mucosal extract was bound efficiently to vitamin B 12 -sepharose without significant change in its nature to produce IF-vitamin B 12 -sepharose. The purification of the intestinal receptor for the IF-vitamin B 12 complex was performed by the affinity chromatography using the IF-vitamin B 12 -sepharose as the affinity adsorbent. As a result of admixing the gastric mucosal extract sample with B 12 -sepharose while stirring for 4 hours, the adsorption was performed without any break through. Further, it was recognized that the B 12 -bound protein purified by the affinity chromatography using B 12 -sepharose was not much changed as compared with that before purification. Furthermore, it was recognized that IF-B 12 -sepharose was able to be made by binding IF with B 12 -sepharose which was made by coupling B 12 with the market-available AH-sepharose. The IF-B 12 -sepharose was washed with buffer solution, and then was loaded with the small intestine mucosal extract. Thereafter, the receptor was eluted by making di-valent cation inert with the buffer solution. After the removal of EDTA in the eluted solution by dialysis, the activity of the receptor was measured. 48.5% of the receptor activity loaded was recovered by the elution with EDTA. The specific activity of the receptor represented by the final amount of B 12 (pg)/the amount of protein (mg) in the purified substance was 335 folds of the original activity. (Iwakiri, K.)

  8. Measurements of vitamin B12 in human blood serum using resonance Raman spectroscopy

    Science.gov (United States)

    Tsiminis, G.; Schartner, E. P.; Brooks, J. L.; Hutchinson, M. R.

    2016-12-01

    Vitamin B12 (cobalamin and its derivatives) deficiency has been identified as a potential modifiable risk factor for dementia and Alzheimer's disease. Chronic deficiency of vitamin B12 has been significantly associated with an increased risk of cognitive decline. An effective and efficient method for measuring vitamin B12 concentration in human blood would enable ongoing tracking and assessment of this potential modifiable risk factor. In this work we present an optical sensor based on resonance Raman spectroscopy for rapid measurements of vitamin B12 in human blood serum. The measurement takes less than a minute and requires minimum preparation (centrifuging) of the collected blood samples.

  9. Status of Vitamin B12 and Folate among the Urban Adult Population in South India.

    Science.gov (United States)

    Sivaprasad, M; Shalini, T; Balakrishna, N; Sudarshan, M; Lopamudra, P; Suryanarayana, P; Arlappa, N; Ravikumar, B P; Radhika, M S; Reddy, G Bhanuprakash

    2016-01-01

    Deficiency of vitamin B12 (B12) and folate (FA) leads to a wide spectrum of disorders that affect all age groups. However, reports on B12 and FA status in healthy adults in India are limited. Hence, we determined the plasma levels and dietary intake of B12 and FA in the adult population. We conducted a community-based cross-sectional study in an urban setup among 630 apparently healthy adults distributed into 3 age groups: 21-40, 41-60 and >60 years. Plasma concentrations of B12 and FA were analyzed by radio immunoassay and dietary intake by 24-hour recall method. The overall prevalence of FA deficiency was 12%, but there was no significant difference in plasma FA concentrations among the groups. While the overall prevalence of B12 deficiency was 35%, it was significantly higher in the 21-40 (44%) and 41-60 age groups (40%) when compared with the >60 group (30%). B12 deficiency was higher in vegetarians (54%) compared to those consuming mixed diet (31%), and the reverse was the case with FA. However, the dietary intakes of FA and B12 were not significantly different among the groups. These results indicate a higher prevalence of B12 deficiency in apparently healthy adults in an urban setup. © 2015 S. Karger AG, Basel.

  10. Atopy, asthma, and lung function in relation to folate and vitamin B(12) in adults

    DEFF Research Database (Denmark)

    Thuesen, B H; Husemoen, L L N; Ovesen, L

    2010-01-01

    Recent studies suggested low serum folate and impaired folate metabolism as potential risk factors for development of asthma and atopic disease, but the results are inconsistent. The aim of this study was to investigate the relations of markers of folate and vitamin B12 (B12) deficiency with diff......Recent studies suggested low serum folate and impaired folate metabolism as potential risk factors for development of asthma and atopic disease, but the results are inconsistent. The aim of this study was to investigate the relations of markers of folate and vitamin B12 (B12) deficiency...

  11. The Antibody Response of Pregnant Cameroonian Women to VAR2CSA ID1-ID2a, a Small Recombinant Protein Containing the CSA-Binding Site

    Science.gov (United States)

    Babakhanyan, Anna; Leke, Rose G. F.; Salanti, Ali; Bobbili, Naveen; Gwanmesia, Philomina; Leke, Robert J. I.; Quakyi, Isabella A.; Chen, John J.; Taylor, Diane Wallace

    2014-01-01

    In pregnant women, Plasmodium falciparum-infected erythrocytes expressing the VAR2CSA antigen bind to chondroitin sulfate A in the placenta causing placental malaria. The binding site of VAR2CSA is present in the ID1-ID2a region. This study sought to determine if pregnant Cameroonian women naturally acquire antibodies to ID1-ID2a and if antibodies to ID1-ID2a correlate with absence of placental malaria at delivery. Antibody levels to full-length VAR2CSA and ID1-ID2a were measured in plasma samples from 745 pregnant Cameroonian women, 144 Cameroonian men, and 66 US subjects. IgM levels and IgG avidity to ID1-ID2a were also determined. As expected, antibodies to ID1-ID2a were absent in US controls. Although pregnant Cameroonian women developed increasing levels of antibodies to full-length VAR2CSA during pregnancy, no increase in either IgM or IgG to ID1-ID2a was observed. Surprisingly, no differences in antibody levels to ID1-ID2a were detected between Cameroonian men and pregnant women. For example, in rural settings only 8–9% of males had antibodies to full-length VAR2CSA, but 90–96% had antibodies to ID1-ID2a. In addition, no significant difference in the avidity of IgG to ID1-ID2a was found between pregnant women and Cameroonian men, and no correlation between antibody levels at delivery and absence of placental malaria was found. Thus, the response to ID1-ID2a was not pregnancy specific, but predominantly against cross-reactivity epitopes, which may have been induced by other PfEMP1 antigens, malarial antigens, or microbes. Currently, ID1-ID2a is a leading vaccine candidate, since it binds to the CSA with the same affinity as the full-length molecule and elicits binding-inhibitory antibodies in animals. Further studies are needed to determine if the presence of naturally acquired cross-reactive antibodies in women living in malaria endemic countries will alter the response to ID1-ID2a following vaccination with ID1-ID2a. PMID:24505415

  12. The antibody response of pregnant Cameroonian women to VAR2CSA ID1-ID2a, a small recombinant protein containing the CSA-binding site.

    Directory of Open Access Journals (Sweden)

    Anna Babakhanyan

    Full Text Available In pregnant women, Plasmodium falciparum-infected erythrocytes expressing the VAR2CSA antigen bind to chondroitin sulfate A in the placenta causing placental malaria. The binding site of VAR2CSA is present in the ID1-ID2a region. This study sought to determine if pregnant Cameroonian women naturally acquire antibodies to ID1-ID2a and if antibodies to ID1-ID2a correlate with absence of placental malaria at delivery. Antibody levels to full-length VAR2CSA and ID1-ID2a were measured in plasma samples from 745 pregnant Cameroonian women, 144 Cameroonian men, and 66 US subjects. IgM levels and IgG avidity to ID1-ID2a were also determined. As expected, antibodies to ID1-ID2a were absent in US controls. Although pregnant Cameroonian women developed increasing levels of antibodies to full-length VAR2CSA during pregnancy, no increase in either IgM or IgG to ID1-ID2a was observed. Surprisingly, no differences in antibody levels to ID1-ID2a were detected between Cameroonian men and pregnant women. For example, in rural settings only 8-9% of males had antibodies to full-length VAR2CSA, but 90-96% had antibodies to ID1-ID2a. In addition, no significant difference in the avidity of IgG to ID1-ID2a was found between pregnant women and Cameroonian men, and no correlation between antibody levels at delivery and absence of placental malaria was found. Thus, the response to ID1-ID2a was not pregnancy specific, but predominantly against cross-reactivity epitopes, which may have been induced by other PfEMP1 antigens, malarial antigens, or microbes. Currently, ID1-ID2a is a leading vaccine candidate, since it binds to the CSA with the same affinity as the full-length molecule and elicits binding-inhibitory antibodies in animals. Further studies are needed to determine if the presence of naturally acquired cross-reactive antibodies in women living in malaria endemic countries will alter the response to ID1-ID2a following vaccination with ID1-ID2a.

  13. Vitamin B(12) Immunoassay on Roche Elecsys 2010: Effects of High Excess Concentration of Serum Vitamin B(12) in CKD Patients on Parenteral Administration.

    Science.gov (United States)

    Basu, Surupa; Chaudhuri, Subimal

    2011-10-01

    Vitamin B(12) being water soluble is excreted in the urine when administered in excess. The probability of finding an abnormally excess serum concentration would be almost surreal. We report a peculiar clinical situation that may impact the vitamin B(12) immunoassay on the Roche Elecsys 2010 due to excess analyte concentration. In separate episodes (Feb and June 2010), the Biochemistry laboratory of a tertiary-care hospital, Kolkata, India, encountered two critically ill patients with background chronic kidney disease (CKD), low urine output, and on cyanocoabalamin supplementation, who had serum vitamin B(12) concentrations far exceeding expected values; even post dialysis. The B(12) assays (pmol/l) were performed using electrochemiluminiscence immunoassay on Roche Elecsys 2010, the assay validity confirmed by concomitant quality control runs. The immunoassays failed to deliver results, flagged with "signal level below limit". Biotin therapy was ruled out as a possible interferent. In the first episode, re-assay of a repeat draw yielded same outcome; outsourcing on Immulite provided concentration of >738 pmol/l. Serial dilution gave result of >29520 pmol/l on Elecsys 2010. In the second, we gained from past experience. Vitamin B(12) concentration >59040 pmol/l was conveyed to the treating nephrologist the very day. The B(12) immunoassay on the Elecsys 2010 employs sequential incubation steps for competitive binding that is compromised in the event of abnormally excess B(12) concentration in patient sera akin to the prozone effect. This knowledge may be beneficial while assaying sera of CKD patients to avoid financial loss due unnecessary repeats and delay in turnaround time.

  14. Identification and analysis of cytochrome P450IID6 antigenic sites recognized by anti-liver-kidney microsome type-1 antibodies (LKM1).

    Science.gov (United States)

    Yamamoto, A M; Cresteil, D; Boniface, O; Clerc, F F; Alvarez, F

    1993-05-01

    Anti-liver-kidney microsome type-1 antibodies (LKM1), present in sera from a group of patients with autoimmune hepatitis, are directed against P450IID6. Previous work, using cDNA constructions spanning most of the P450IID6 protein defined the main immunogenic site between the amino acids (aa), 254-271 and predicted the presence of other putative immunogenic sites in the molecule. Fusion proteins from new cDNA constructions, spanning so-far-untested regions between aa 1-125 and 431-522, were not recognized by LKM1-positive sera. Synthetic peptides, representing sequences from putative immunogenic regions or previously untested regions, allowed a precise definition of four antigenic sites located between peptides 257-269, 321-351, 373-389 and 410-429, which were recognized, respectively, by 14, 8, 1 and 2 out of 15 LKM1-positive sera tested. The minimal sequence of the main antigenic site (peptide 257-269) recognized by the autoantibody was established to be WDPAQPPRD (peptide 262-270). In addition, deletion and replacement experiments showed that aa 263 (Asp) was essential for the binding of the autoantibody to peptide 262-270. Analysis of the second most frequently recognized peptide between aa 321-351, was performed using peptides 321-339 and 340-351 in competitive inhibition studies. Complete elimination of antibody binding to peptide 321-351 obtained by absorption of both shorter peptides indicated that peptide 321-351 is a discontinuous antigenic site. LKM1-positive sera reacting against peptide 321-351 recognized either both the shorter peptides or just one of them preferentially. Results of the present study suggest that the production of LKM1 antibodies is an antigen-driven, poly- or oligoclonal B cell response. The identification of antigenic sites will allow: (i) the development of specific diagnostic tests and (ii) further studies on the pathogenic value of LKM1 antibodies in autoimmune hepatitis.

  15. The Singer's and the Clinician's Perspective on Vitamin B12 Treatment for Vocal Benefits.

    Science.gov (United States)

    Shoffel-Havakuk, Hagit; Lava, Christian X; Hapner, Edie R; O'Dell, Karla; Reder, Lindsay; Johns, Michael M

    2018-01-03

    There is a belief among vocalists that there are voice benefits from vitamin B 12 treatment. Yet there are no previous reports regarding vitamin B 12 effects on voice. To assess the prevalence of vitamin B 12 use among singers and their beliefs regarding vitamin B 12 therapy. Anonymous online survey administered to singers, singing-teachers, speech-language pathologists, and laryngologists. A total of 192 participants completed the surveys; 128 singers (68 singing-teachers, 30 speech-language pathologists) and 64 laryngologists. Among singers, 12% have perceived voice benefits from vitamin B 12 treatment taken for any reason. Four percent used vitamin B 12 for voice benefits; all perceived voice benefits as a result. The leading voice benefits were improved stamina, reduced effort, confidence, and control. Nineteen percent of the singers would recommend vitamin B 12 treatment to a friend; 15% of the singing-teachers would recommend it to a student. Among laryngologists, 33% been asked by a singer to prescribe vitamin B 12 for voice benefits; 9% have prescribed it in the past. Yet only 3% would you recommend it to a patient. When asked "Do you believe vitamin B 12 therapy improves vocal performance?" 31% of the singers responded "Yes," compared with none in the laryngologists. When asked "Do you think the singing community believes vitamin B 12 therapy improves vocal performance?" 26% of the singers responded "Yes," compared with 53% of the laryngologists (P = 0.0002). There is a discrepancy between the singers' and the laryngologists' beliefs regarding vocal benefits perceived by vitamin B 12 . Blinded randomized trials are required to verify or refute this belief. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  16. The antibody response in the bovine mammary gland is influenced by the adjuvant and the site of subcutaneous vaccination

    NARCIS (Netherlands)

    Boerhout, Eveline M.; Koets, Ad P.; Mols-Vorstermans, Tanja G.T.; Nuijten, Piet J.M.; Hoeijmakers, Mathieu J.H.; Rutten, Victor P.M.G.; Bijlsma, Jetta J.E.

    2018-01-01

    Intramammary infections in cattle resulting in mastitis have detrimental effects on cows' well-being, lifespan and milk production. In the host defense against S. aureus mastitis antibodies are thought to play an important role. To explore potential ways to increase antibody titers in the bovine

  17. Site-specific conjugation and labelling of prostate antibody 7E11C5.3 (CYT-351) with technetium-99m

    International Nuclear Information System (INIS)

    Stalteri, M.A.; Mather, S.J.; Belinka, B.A.; Coughlin, D.J.; Chengazi, V.U.; Britton, K.E.

    1997-01-01

    Attachment of chelating agents to the sugar residues of antibodies for subsequent radiolabelling is an attractive approach since it may have less effect on the immunoreactivity than attachment through lysine residues, which are distributed throughout the antibody and may be present near the antigen binding site. We have attached a new hydrazide-linked chelator CYT-395 (Cytogen Corp., Princeton, N.J.) to the sugar residues of the anti-prostate monoclonal antibody 7E11C5.3 and optimised the conditions for labelling the conjugate with technetium-99m in order to compare the conjugate to 7E11C5.3 antibody labelled directly with technetium using a mercaptoethanol reduction technique. Labelling yields of 70%-90% were obtained at specific activities up to 2000 MBq/mg antibody. The stability of the technetium-labelled conjugate in plasma or to a challenge with 0.1 or 1.0 mM cysteine was similar to that of direct-labelled antibody. In nine patients with prostate cancer, the plasma clearance of the labelled conjugate followed a two-compartment model, with an average β-phase half-life of 31.4±3.9 h. The average urinary clearance at 24 h was 15.3±5.0% of the injected dose. In this group of patients there was no significant difference between the blood and urine clearance of the labelled conjugate, and the clearances of the direct-labelled antibody. (orig.). With 5 figs

  18. Smoking Discriminately Changes the Serum Active and Non-Active Forms of Vitamin B12.

    Science.gov (United States)

    Shekoohi, Niloofar; Javanbakht, Mohammad Hassan; Sohrabi, Marjan; Zarei, Mahnaz; Mohammadi, Hamed; Djalali, Mahmoud

    2017-06-01

    Smoking may modify the appetite, and consequently affect nutrient intake and serum micronutrients. The effect of smoking on vitamin B12 status has been considered in several studies. The research proposed that organic nitrites, nitro oxide, cyanides, and isocyanides of cigarette smoke interfere with vitamin B12 metabolism, and convert it to inactive forms. This research was carried out to determine the serum level of active and inactive forms of vitamin B12 in male smokers in comparison with male nonsmokers. This is a case-control study, in which the participants were 85 male smokers and 85 male nonsmokers. The serum levels of total and active form of vitamin B12 were measured. Dietary intake was recorded by a quantitative food frequency questionnaire and one-day 24-hour dietary recall method. Independent two sample T test was used to compare quantitative variables between the case and control groups. The serum level of total vitamin B12 was not significantly different between two groups, but serum level of active form of vitamin B12 in the smoking group was significantly lower than non-smoking group (Psmokers in the Iranian community. The results of this study identified that serum level of total vitamin B12 might be not different between smoking and non-smoking people, but the function of this vitamin is disturbed in the body of smokers through the reduction of serum level of active form of vitamin B12.

  19. The complete coenzyme B12 biosynthesis gene cluster of Lactobacillus reuteri CRL 1098

    NARCIS (Netherlands)

    Santos, dos F.; Vera, J.L.; Heijden, van der R.; Valdez, G.F.; Vos, de W.M.; Sesma, F.; Hugenholtz, J.

    2008-01-01

    The coenzyme B12 production pathway in Lactobacillus reuteri has been deduced using a combination of genetic, biochemical and bioinformatics approaches. The coenzyme B12 gene cluster of Lb. reuteri CRL1098 has the unique feature of clustering together the cbi, cob and hem genes. It consists of 29

  20. Vitamin B12 status and its association with Helicobacter pylori infection in alcohol dependent patients

    NARCIS (Netherlands)

    van Oijen, Martijn G. H.; Laheij, Robert J. F.; de Jong, Cor A. J.; Peters, Wilbert H. M.; Jansen, Jan B. M. J.

    2004-01-01

    Both infection with Helicobacter pylori and alcohol abuse have been associated with low vitamin B12 serum levels. The interaction between both risk factors is unknown. The aim of this study was to determine whether Helicobacter pylori infection is associated with low vitamin B12 levels in alcohol

  1. Low vitamin B-12 status and risk of cognitive decline in older adults

    DEFF Research Database (Denmark)

    Clarke, Robert; Birks, Jacqueline; Nexo, Ebba

    2007-01-01

    BACKGROUND: Elevated total homocysteine (tHcy) concentrations have been associated with cognitive impairment, but it is unclear whether low vitamin B-12 or folate status is responsible for cognitive decline. OBJECTIVE: We examined the associations of cognitive decline with vitamin B-12 and folate...

  2. Vitamin B12 deficiency presenting as an acute confusional state: A ...

    African Journals Online (AJOL)

    Results: We report a case of a 44 year old female patient referred to the haematology unit with vitamin B12 deficiency presenting as an acute confusional state or delirium. Total resolution of the psychiatric symptoms occurred following parenteral vitamin B12 replacement therapy. Conclusion: This case report highlights one ...

  3. Loss of vitamin B(12) in fish (round herring) meats during various cooking treatments.

    Science.gov (United States)

    Nishioka, Michiko; Kanosue, Fuki; Yabuta, Yukinori; Watanabe, Fumio

    2011-01-01

    The loss of vitamin B(12) in round herring meats during various cooking treatments was evaluated. Although amounts of vitamin B(12) were three times greater in the viscera (37.5 ± 10.6 µg/100 g fresh weight) than in the meats, about 73% of total vitamin B(12) found in the whole fish body (except for head and bones) were recovered in the meats (5.1 ± 1.0 µg of vitamin B(12)). The vitamin B(12) contents of the round herring's meats were significantly decreased up to ~62% during cooking by grilling, boiling, frying, steaming, and microwaving. There was, however, no loss of vitamin B(12) during vacuum-packed pouch cooking. Model experiment using hydroxocobalamin suggest that loss of vitamin B(12) is dependent on the degree of temperature and time used in conventional cooking, and is further affected by the concomitant ingredients of food. Retention of vitamin B(12) was not dependent on vacuum or temperature (or both) used in the vacuum-packed pouch cooking.

  4. Genetic determinants of serum vitamin B12 and their relation to body mass index

    DEFF Research Database (Denmark)

    Allin, Kristine H.; Friedrich, Nele; Pietzner, Maik

    2017-01-01

    (-4)). We found no support for a causal role of decreased serum vitamin B12 levels in obesity. However, our study suggests that FUT2, through its regulation of the cross-talk between gut microbes and the human host, might explain a part of the observational association between serum vitamin B12 and BMI....

  5. Vitamin B 12 levels in patients with type 2 diabetes mellitus on ...

    African Journals Online (AJOL)

    Methods: Serum vitamin B12 level was determined using high performance liquid chromatography (HPLC) in 81 T2DM patients who have been on metformin for 5 years or more. Vitamin B12 deficiency was defined as serum concentration of 300 pg/dl as normal.

  6. Reposição de vitamina B12 reduz comportamento depressivo induzido em ratos jovens = Vitamin B12 replacement therapy reduces induced depressive behavior in young rats

    Directory of Open Access Journals (Sweden)

    Brito, Adriana Maria de Oliveira

    2016-01-01

    Conclusões: A depleção suave de vitamina B12 na dieta, em nível não indutor de anemia, favoreceu o estado depressivo em ratos jovens, enquanto a sua suplementação na situação de depleção reverteu esse quadro. Em condições de nutrição adequada, entretanto, a suplementação dessa vitamina não exerceu efeito sobre o estado depressivo. Estes resultados estimulam a realização de mais estudos que aprofundem a avaliação das relações entre vitamina B12 e depressão em jovens. Além disso, este estudo também abre perspectivas para um novo modelo experimental de depressão, induzida por depleção de vitamina B12

  7. Low vitamin B-12 status and risk of cognitive decline in older adults

    DEFF Research Database (Denmark)

    Clarke, Robert; Birks, Jacqueline; Nexo, Ebba

    2007-01-01

    remained significant. CONCLUSIONS: Low vitamin B-12 status was associated with more rapid cognitive decline. Randomized trials are required to determine the relevance of vitamin B-12 supplementation for prevention of dementia. Udgivelsesdato: 2007-Nov......BACKGROUND: Elevated total homocysteine (tHcy) concentrations have been associated with cognitive impairment, but it is unclear whether low vitamin B-12 or folate status is responsible for cognitive decline. OBJECTIVE: We examined the associations of cognitive decline with vitamin B-12 and folate...... status in a longitudinal cohort study performed from 1993 to 2003 in Oxford, United Kingdom. DESIGN: Cognitive function was assessed with the Mini-Mental State Examination on >/=3 occasions during 10 y and related to serum concentrations of vitamin B-12, holotranscobalamin (holoTC), tHcy, methylmalonic...

  8. B12 deficiency increases with age in hospitalized patients: a study on 14,904 samples.

    Science.gov (United States)

    Mézière, Anthony; Audureau, Etienne; Vairelles, Stéphane; Krypciak, Sébastien; Dicko, Michèle; Monié, Marguerite; Giraudier, Stéphane

    2014-12-01

    Cobalamin deficiency is responsible for hematological, neurological, neurocognitive, and neuropsychiatric impairments and is a risk factor for cardiovascular diseases, particularly in the elderly people. In order to determine B12 status in old inpatients, a total number of 14,904 hospitalized patients in whom B12 measurements were performed in five hospitals in the Paris metropolitan area were included from January 1, 2011 to December 31, 2011. The aims of the study were to determine whether age had an impact on B12 and folate deficiencies and to evaluate correlations between B12 and biological parameters-folate, hemoglobin, mean cell volume, homocystein (tHcy)-and age. Patients were aged 70.3±19.5 years. Low B12 concentration ( 17 µmol/L), 20.4% had low folate concentration (folate 17 µmol/L), and 4.7% of patients were both functional B12 and folate deficient. The B12 or folate deficient patients had lower mean cell volume level than nondeficient patients. Increase in mean cell volume and tHcy concentrations with age and decrease in B12, folate, and hemoglobin levels with age were observed. Frequency of functional B12 deficiency was 9.6% in patients aged 30-60 years and 14.2% in patients over 90 years. Frequency of functional folate deficiency was 9.5% in 30-60 years and 12.1% in >90 years. In inpatients, functional B12 deficiency and functional folate deficiency increase with age and are not associated with anemia or macrocytosis. False vitamin B deficiencies are frequent. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. The Folate-Vitamin B12 Interaction, Low Hemoglobin, and the Mortality Risk from Alzheimer's Disease.

    Science.gov (United States)

    Min, Jin-Young; Min, Kyoung-Bok

    2016-03-21

    Abnormal hemoglobin levels are a risk factor for Alzheimer's disease (AD). Although the mechanism underlying these associations is elusive, inadequate micronutrients, particularly folate and vitamin B12, may increase the risk for anemia, cognitive impairment, and AD. In this study, we investigated whether the nutritional status of folate and vitamin B12 is involved in the association between low hemoglobin levels and the risk of AD mortality. Data were obtained from the 1999-2006 National Health and Nutrition Examination Survey (NHANES) and the NHANES (1999-2006) Linked Mortality File. A total of 4,688 participants aged ≥60 years with available baseline data were included in this study. We categorized three groups based on the quartiles of folate and vitamin B12 as follows: Group I (low folate and vitamin B12); Group II (high folate and low vitamin B12 or low folate and high vitamin B12); and Group III (high folate and vitamin B12). Of 4,688 participants, 49 subjects died due to AD. After adjusting for age, sex, ethnicity, education, smoking history, body mass index, the presence of diabetes or hypertension, and dietary intake of iron, significant increases in the AD mortality were observed in Quartile1 for hemoglobin (HR: 8.4, 95% CI: 1.4-50.8), and the overall risk of AD mortality was significantly reduced with increases in the quartile of hemoglobin (p for trend = 0.0200), in subjects with low levels of both folate and vitamin B12 at baseline. This association did not exist in subjects with at least one high level of folate and vitamin B12. Our finding shows the relationship between folate and vitamin B12 levels with respect to the association between hemoglobin levels and AD mortality.

  10. Vitamin B12 supplement alleviates N'-nitrosodimethylamine-induced hepatic fibrosis in rats.

    Science.gov (United States)

    Ahmad, Areeba; Afroz, Nishat; Gupta, Umesh D; Ahmad, Riaz

    2014-01-10

    Abstract Context: Altered vitamin B 12 levels have been correlated with hepatotoxicity; however, further evidence is required to establish its protective role. Objective: To evaluate the effects of vitamin B 12 supplement in protecting N'-nitrosodimethylamine (NDMA)-induced hepatic fibrosis in Wistar rats. Materials and methods: Hepatic fibrosis was induced by administering NDMA in doses of 10 mg/kg body weight thrice a week for 21 days. Another group received equal doses (10 mg/kg body weight) of vitamin B 12 subsequent to NDMA treatment. Animals from either group were sacrificed weekly from the start of the treatment along with their respective controls. Progression of hepatic fibrosis, in addition to the effect of vitamin B 12 , was assessed biochemically for liver function biomarkers, liver glycogen, hydroxyproline (HP) and B 12 reserves along with histopathologically by hematoxylin and eosin (H & E) as well immunohistochemical staining for α-SMA expression. Results and discussion: Elevation in the levels of aminotransferases, SALP, total bilirubin and HP was observed in NDMA treated rats, which was concomitant with remarkable depletion in liver glycogen and B 12 reserves (p < 0.05). Liver biopsies also demonstrated disrupted lobular architecture, collagen amassing and intense fibrosis by NDMA treatment. Immunohistochemical staining showed the presence of activated stellate cells that was dramatically increased up to day 21 in fibrotic rats. Following vitamin B 12 treatment, liver function biomarkers, glycogen contents and hepatic vitamin B 12 reserves were restored in fibrotic rats, significantly. Vitamin B 12 administration also facilitated restoration of normal liver architecture. Conclusion: These findings provide interesting new evidence in favor of protective role for vitamin B 12 against NDMA-induced hepatic fibrosis in rats.

  11. Vitamin B12 intake and status and cognitive function in elderly people.

    Science.gov (United States)

    Doets, Esmée L; van Wijngaarden, Janneke P; Szczecińska, Anna; Dullemeijer, Carla; Souverein, Olga W; Dhonukshe-Rutten, Rosalie A M; Cavelaars, Adrienne E J M; van 't Veer, Pieter; Brzozowska, Anna; de Groot, Lisette C P G M

    2013-01-01

    Current recommendations on vitamin B12 intake vary from 1.4 to 3.0 μg per day and are based on the amount needed for maintenance of hematologic status or on the amount needed to compensate obligatory losses. This systematic review evaluates whether the relation between vitamin B12 intake and cognitive function should be considered for underpinning vitamin B12 recommendations in the future. The authors summarized dose-response evidence from randomized controlled trials and prospective cohort studies on the relation of vitamin B12 intake and status with cognitive function in adults and elderly people. Two randomized controlled trials and 6 cohort studies showed no association or inconsistent associations between vitamin B12 intake and cognitive function. Random-effects meta-analysis showed that serum/plasma vitamin B12 (50 pmol/L) was not associated with risk of dementia (4 cohort studies), global cognition z scores (4 cohort studies), or memory z scores (4 cohort studies). Although dose-response evidence on sensitive markers of vitamin B12 status (methylmalonic acid and holotranscobalamin) was scarce, 4 of 5 cohort studies reported significant associations with risk of dementia, Alzheimer's disease, or global cognition. Current evidence on the relation between vitamin B12 intake or status and cognitive function is not sufficient for consideration in the development of vitamin B12 recommendations. Further studies should consider the selection of sensitive markers of vitamin B12 status. © The Author 2012. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Contribution of tryptophan residues to the combining site of a monoclonal anti dinitrophenyl spin-label antibody

    International Nuclear Information System (INIS)

    Anglister, J.; Bond, M.W.; Frey, T.; Leahy, D.; Levitt, M.; McConnell, H.M.; Rule, G.S.; Tomasello, J.; Whittaker, M.

    1987-01-01

    Two Fab fragments of the monoclonal anti dinitrophenyl (DNP) spin-label antibody AN02 were prepared by recombination of specifically deuterated heavy and light chains. In the recombinant H(I)L(II) all the tyrosines and phenylalanines were perdeuterated as were the tryptophan residues of the heavy chain. In the recombinant H(II)L(I) all the tyrosines and phenylalanines were perdeuterated as were the tryptophan residues of the light chain. Saturation of three resonances of H(I)L(II), assigned to tryptophan protons of the light chain, resulted in magnetization transfer to the aromatic proton at position 6 of the DNP ring and to the CH2 protons of the glycines linked to the DNP in a diamagnetic hapten (DNP-DG). Saturation of three resonances of H(II)L(I) assigned to tryptophan protons of the heavy chain resulted in magnetization transfer to the CH2 protons of the glycines in DNP-DG. From the dependence of the magnetization transfer on the irradiation time, the cross relaxation rates between the involved protons were estimated. The inferred distances between these protons of the hapten and certain tryptophan protons are 3-4 A. It is concluded that in the combining site of AN02 there is one tryptophan from the light chain and one tryptophan from the heavy chain that are very near the hapten. When all tyrosines and phenylalanines were perdeuterated and all tryptophan aromatic protons were deuterated except for the protons at positions 2 and 5, titration of the Fab fragments with variable amounts of paramagnetic hapten showed that one proton from the light chain tryptophan is near (less than 7 A) the unpaired electron and that three other protons are significantly closer than 15 A

  13. Contribution of tryptophan residues to the combining site of a monoclonal anti dinitrophenyl spin-label antibody

    Energy Technology Data Exchange (ETDEWEB)

    Anglister, J.; Bond, M.W.; Frey, T.; Leahy, D.; Levitt, M.; McConnell, H.M.; Rule, G.S.; Tomasello, J.; Whittaker, M.

    1987-09-22

    Two Fab fragments of the monoclonal anti dinitrophenyl (DNP) spin-label antibody AN02 were prepared by recombination of specifically deuterated heavy and light chains. In the recombinant H(I)L(II) all the tyrosines and phenylalanines were perdeuterated as were the tryptophan residues of the heavy chain. In the recombinant H(II)L(I) all the tyrosines and phenylalanines were perdeuterated as were the tryptophan residues of the light chain. Saturation of three resonances of H(I)L(II), assigned to tryptophan protons of the light chain, resulted in magnetization transfer to the aromatic proton at position 6 of the DNP ring and to the CH2 protons of the glycines linked to the DNP in a diamagnetic hapten (DNP-DG). Saturation of three resonances of H(II)L(I) assigned to tryptophan protons of the heavy chain resulted in magnetization transfer to the CH2 protons of the glycines in DNP-DG. From the dependence of the magnetization transfer on the irradiation time, the cross relaxation rates between the involved protons were estimated. The inferred distances between these protons of the hapten and certain tryptophan protons are 3-4 A. It is concluded that in the combining site of AN02 there is one tryptophan from the light chain and one tryptophan from the heavy chain that are very near the hapten. When all tyrosines and phenylalanines were perdeuterated and all tryptophan aromatic protons were deuterated except for the protons at positions 2 and 5, titration of the Fab fragments with variable amounts of paramagnetic hapten showed that one proton from the light chain tryptophan is near (less than 7 A) the unpaired electron and that three other protons are significantly closer than 15 A.

  14. Site-directed immobilization of a genetically engineered anti-methotrexate antibody via an enzymatically introduced biotin label significantly increases the binding capacity of immunoaffinity columns.

    Science.gov (United States)

    Davenport, Kaitlynn R; Smith, Christopher A; Hofstetter, Heike; Horn, James R; Hofstetter, Oliver

    2016-05-15

    In this study, the effect of random vs. site-directed immobilization techniques on the performance of antibody-based HPLC columns was investigated using a single-domain camelid antibody (VHH) directed against methotrexate (MTX) as a model system. First, the high flow-through support material POROS-OH was activated with disuccinimidyl carbonate (DSC), and the VHH was bound in a random manner via amines located on the protein's surface. The resulting column was characterized by Frontal Affinity Chromatography (FAC). Then, two site-directed techniques were explored to increase column efficiency by immobilizing the antibody via its C-terminus, i.e., away from the antigen-binding site. In one approach, a tetra-lysine tail was added, and the antibody was immobilized onto DSC-activated POROS. In the second site-directed approach, the VHH was modified with the AviTag peptide, and a biotin-residue was enzymatically incorporated at the C-terminus using the biotin ligase BirA. The biotinylated antibody was subsequently immobilized onto NeutrAvidin-derivatized POROS. A comparison of the FAC analyses, which for all three columns showed excellent linearity (R(2)>0.999), revealed that both site-directed approaches yield better results than the random immobilization; the by far highest efficiency, however, was determined for the immunoaffinity column based on AviTag-biotinylated antibody. As proof of concept, all three columns were evaluated for quantification of MTX dissolved in phosphate buffered saline (PBS). Validation using UV-detection showed excellent linearity in the range of 0.04-12μM (R(2)>0.993). The lower limit of detection (LOD) and lower limit of quantification (LLOQ) were found to be independent of the immobilization strategy and were 40nM and 132nM, respectively. The intra- and inter-day precision was below 11.6%, and accuracy was between 90.7% and 112%. To the best of our knowledge, this is the first report of the AviTag-system in chromatography, and the first

  15. A two-site immunoradiometric assay for human pregnancy-associated plasma protein A (PAPP-A) using monoclonal antibodies

    International Nuclear Information System (INIS)

    Mowles, E.A.; Pinto-Furtado, L.G.; Bolton, A.E.

    1986-01-01

    A rapid, sensitive immunoradiometric assay has been developed for human pregnancy-associated plasma protein A (PAPP-A) using a purified mouse monoclonal antibody as the tracer and a rabbit polyclonal antibody to this protein in the solid-phase antibody preparation. The assay showed no measurable cross-reaction (< 0.1%) against a range of purified human placental proteins, and a good correlation with a previously described radioimmunoassay procedure when tested on samples taken throughout normal human pregnancies. No PAPP-A-like immunological activity could be detected in sera from non-pregnant women, confirming the absence of this protein from the circulation outside pregnancy. (Auth.)

  16. Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity

    International Nuclear Information System (INIS)

    Fenech, Michael

    2012-01-01

    Folate plays a critical role in the prevention of uracil incorporation into DNA and hypomethylation of DNA. This activity is compromised when vitamin B12 concentration is low because methionine synthase activity is reduced, lowering the concentration of S-adenosyl methionine (SAM) which in turn may diminish DNA methylation and cause folate to become unavailable for the conversion of dUMP to dTMP. The most plausible explanation for the chromosome-breaking effect of low folate is excessive uracil misincorporation into DNA, a mutagenic lesion that leads to strand breaks in DNA during repair. Both in vitro and in vivo studies with human cells clearly show that folate deficiency causes expression of chromosomal fragile sites, chromosome breaks, excessive uracil in DNA, micronucleus formation, DNA hypomethylation and mitochondrial DNA deletions. In vivo studies show that folate and/or vitamin B12 deficiency and elevated plasma homocysteine (a metabolic indicator of folate deficiency) are significantly correlated with increased micronucleus formation and reduced telomere length respectively. In vitro experiments indicate that genomic instability in human cells is minimised when folic acid concentration in culture medium is greater than 100 nmol/L. Intervention studies in humans show (a) that DNA hypomethylation, chromosome breaks, uracil incorporation and micronucleus formation are minimised when red cell folate concentration is greater than 700 nmol/L and (b) micronucleus formation is minimised when plasma concentration of vitamin B12 is greater than 300 pmol/L and plasma homocysteine is less than 7.5 μmol/L. These concentrations are achievable at intake levels at or above current recommended dietary intakes of folate (i.e. >400 μg/day) and vitamin B12 (i.e. >2 μg/day) depending on an individual's capacity to absorb and metabolise these vitamins which may vary due to genetic and epigenetic differences.

  17. Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity

    Energy Technology Data Exchange (ETDEWEB)

    Fenech, Michael, E-mail: michael.fenech@csiro.au [CSIRO Food and Nutritional Sciences, PO Box 10041 Adelaide BC, SA 5000 (Australia)

    2012-05-01

    Folate plays a critical role in the prevention of uracil incorporation into DNA and hypomethylation of DNA. This activity is compromised when vitamin B12 concentration is low because methionine synthase activity is reduced, lowering the concentration of S-adenosyl methionine (SAM) which in turn may diminish DNA methylation and cause folate to become unavailable for the conversion of dUMP to dTMP. The most plausible explanation for the chromosome-breaking effect of low folate is excessive uracil misincorporation into DNA, a mutagenic lesion that leads to strand breaks in DNA during repair. Both in vitro and in vivo studies with human cells clearly show that folate deficiency causes expression of chromosomal fragile sites, chromosome breaks, excessive uracil in DNA, micronucleus formation, DNA hypomethylation and mitochondrial DNA deletions. In vivo studies show that folate and/or vitamin B12 deficiency and elevated plasma homocysteine (a metabolic indicator of folate deficiency) are significantly correlated with increased micronucleus formation and reduced telomere length respectively. In vitro experiments indicate that genomic instability in human cells is minimised when folic acid concentration in culture medium is greater than 100 nmol/L. Intervention studies in humans show (a) that DNA hypomethylation, chromosome breaks, uracil incorporation and micronucleus formation are minimised when red cell folate concentration is greater than 700 nmol/L and (b) micronucleus formation is minimised when plasma concentration of vitamin B12 is greater than 300 pmol/L and plasma homocysteine is less than 7.5 {mu}mol/L. These concentrations are achievable at intake levels at or above current recommended dietary intakes of folate (i.e. >400 {mu}g/day) and vitamin B12 (i.e. >2 {mu}g/day) depending on an individual's capacity to absorb and metabolise these vitamins which may vary due to genetic and epigenetic differences.

  18. Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis

    Science.gov (United States)

    Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

    2018-01-01

    AIM To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). METHODS A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori (H. pylori) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. RESULTS Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve (R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. CONCLUSION Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy

  19. Vitamin B-12 treatment of asymptomatic, deficient, elderly Chileans improves conductivity in myelinated periphreal nerves, but high serum folate impairs vitamin B-12 status response assessed by the combined indicator of..

    Science.gov (United States)

    Since 2005 the National Feeding Program for the Elderly (PACAM) in Chile has provided a B12 fortified milk drink (1.7 µg B12/d) which is insufficient to ensure B12 adequacy in many individuals. The objective was to evaluate effects of adding 1 mg B12/d to PACAM vs 1 mg B12/d as a pill with PACAM on ...

  20. Prediction of site-specific interactions in antibody-antigen complexes: the proABC method and server.

    KAUST Repository

    Olimpieri, Pier Paolo; Chailyan, Anna; Tramontano, Anna; Marcatili, Paolo

    2013-01-01

    MOTIVATION: Antibodies or immunoglobulins are proteins of paramount importance in the immune system. They are extremely relevant as diagnostic, biotechnological and therapeutic tools. Their modular structure makes it easy to re-engineer them

  1. Prevalence of mild serum vitamin B12 deficiency in rural and urban Costa Rican young adults Prevalencia de la deficiencia moderada de vitamina B12 sérica en jóvenes adultos de zonas rurales y urbanas de Costa Rica

    Directory of Open Access Journals (Sweden)

    Ileana Holst-Schumacher

    2007-12-01

    Full Text Available OBJECTIVE: Recent studies have shown an increase of mild serum cobalamin (vitamin B12 deficiency in some Latin American countries; however, no data are available from Costa Rica. The purpose of this work was to establish the prevalence of serum vitamin B12 deficiency among Costa Rican young adults and to study some factors that may help explain the serum cobalamin concentrations. METHODS: A cross-sectional survey was conducted among 400 adults aged 20 to 40 years old from urban and rural areas of the central valley of Costa Rica to determine serum vitamin B12 levels. Additionally, cobalamin dietary intake and the detection of Helicobacter pylori IgG antibodies were studied as possible determinants of the serum vitamin B12 concentrations. RESULTS: The mean serum concentration of vitamin B12 was 268 ± 125 pmol/L, and no significant differences were found by gender or area. Study data indicate an overall prevalence of inadequate serum cobalamin levels of 42.4% (11.2% deficient and 31.2% marginal; more than 50% but less than 75% of individuals had an intake of vitamin B12 below the U.S. Estimated Average Requirement (EAR and 61.2% had IgG antibodies to H. pylori. CONCLUSIONS: The prevalence of mild serum vitamin B12 deficiency in young Costa Rican subjects is as high as in other Latin American countries. More investigation should be done to elucidate the etiological factors that are generating deficient and marginal serum cobalamin levels in Costa Rican adults in order to define appropriate public health actions.OBJETIVO: Aunque estudios recientes han demostrado un incremento en el déficit moderado de cobalamina (vitamina B12 sérica en algunos países de América Latina, no hay datos de Costa Rica. El propósito de este trabajo fue determinar la prevalencia de la deficiencia de vitamina B12 sérica en jóvenes adultos de Costa Rica y estudiar algunos factores que pueden ayudar a explicar las concentraciones séricas de cobalamina. MÉTODOS: Se

  2. The Relationship of Vitamin B12 Deficiency and Red Cell Distribution Width-Platelet Ratio

    Directory of Open Access Journals (Sweden)

    Nigar Yilmaz

    2016-09-01

    Full Text Available Objective: We aimed to investigate the relationship between vitamin B12 deficiency and red cell distribution widthplatelet ratio (RPR, and the variations in the parameters on vitamin B12 treatment. Methods: One hundred fifty-four patients with untreated vitamin B12 deficiency (56% men, mean age: 50 ± 12.7 years (untreated group, 86 patients with vitamin B12 deficiency (62% men, mean age: 42 ± 20.7 years on vitamin B12 treatment (treated group, and 92 age- and sex-matched control group (54% men, mean age: 45 ± 15.1 years were included in the study. Hematological parameters were evaluated by the method of laser-based flow cytometric impedance, using an automated blood cell counter (ABX Pentra 120 Hematology Blood Analyzer. Results: RPR was significantly reduced in treated group compared with untreated group (4.88 ± 1.06; 6.13 ± 1.27; p0.05. Conclusion: We proposed that vitamin B12 deficiency has effects on RPR and supplementation with vitamin B12 corrects the RPR levels. J Clin Exp Invest 2016; 7 (3: 211-215

  3. Intestinal synthesis and absorption of vitamin B-12 in channel catfish

    International Nuclear Information System (INIS)

    Limsuwan, T.; Lovell, R.T.

    1981-01-01

    A feeding experiment conducted in a controlled environment and using a vitamin B12-deficient, but otherwise nutritionally complete, purified diet revealed that intestinal microorganisms in channel catfish synthesized approximately 1.4 ng of vitamin B12 per gram of bodyweight per day. Removal of cobalt from the diet or supplementation with an antibiotic (succinylsulfathiazole) significantly reduced the rate of intestinal synthesis and liver stores of vitamin B12. Radiolabeled vitamin B12 in the blood, liver, kidneys, and spleen of fish fed 60Co in the diet indicated that the intestinally synthesized vitamin was absorbed by the fish. The primary route of absorption was directly from the digestive tract into the blood because coprophagy was prevented in the rearing aquariums and the amount of vitamin B12 dissolved in the aquarium water was too low for gill absorption. Dietary supplementation of vitamin B12 was not necessary for normal growth and erythrocyte formation in channel catfish in a 24-week feeding period. A longer period, however, may have caused a vitamin deficiency since liver-stored vitamin B 12 decreased between the 2nd and 24th weeks

  4. Voltammetry of Vitamin B12 on a thin self-assembled monolayer modified electrode

    International Nuclear Information System (INIS)

    Yang Nianjun; Wan Qijin; Wang, Xiaoxia

    2005-01-01

    Vitamin B 12 showed three reduction waves at a thin self-assembled monolayer of mercaptoacetic acid modified gold electrode at 0.21, 0.16, -0.41 V in a 0.01 mol l -1 HCl solution at a scan rate of 100 mV s -1 . The overall electrode reaction followed an ECE mechanism, leading to a total two-electron exchange. The predominant Co(III) form was reduced directly at 0.21 V by a one-electron transfer accomplished by CN - cleavage into the cyanocob(II)alamin. The latter species then equilibrated with the base-off B 12r , which was immediately reduced into B 12s at 0.16 V. The wave at -0.41 V might be a catalytic hydrogen wave. The cathodic peak currents at 0.21 V were controlled by the diffusion of Vitamin B 12 . On the base of its diffusion behavior, the semi-derivate voltammetric method for the detection of Vitamin B 12 was presented. The semi-derivate voltammetric peak current of the wave at 0.21 V was linear with the content of Vitamin B 12 in the range of 4.0 x 10 -9 to 4.0 x 10 -5 mol l -1 . The detection limit was 1.0 x 10 -9 mol l -1 . The proposed method was applied successfully to determine the content of Vitamin B 12 in pharmaceutical preparations

  5. A general review on vitamin B12 deficiency with focus on the situation in Jordan

    International Nuclear Information System (INIS)

    Qutob, M. S.; Takruri, H. R.

    2011-01-01

    Vitamin B 12 (cobalamin) is an essential nutrient that is only obtained from foods of animal origin, such as meat, eggs and dairy products. Vitamin B 12 plays an important role in DNA synthesis and neurological function. Thus its deficiency can lead to several neurological symptoms such as memory loss, dizziness and in severe cases may lead to dementia. Many factors can cause or lead to vitamin B-1 2 deficiency. Among these are malabsorption, several gastron intestinal problems (i.e. celiac disease, Crobn's disease) and gastrointestinal surgeries. diagnosis of vitamin B-1 2 status depends commonly on serum vitamin B 12 which is nonspecific tool for the deficiency. Other more specific tests, which reflect true deficiency, include serum and urine methylmalonic aci de, total serum homocysteine and serum holotranscobalamin. Vitamin B 12 deficiency is a worldwide public health problem; epidemiological studies showed that its prevalence in industrialized countries ranges from 5-60% of the population depending on the used cutoff point of cobalamin level. In Jordan, many reports were published on vitamin B 12 deficiency. However, these reports gave different results of its prevalence ranging from 16-48% depending on the serum vitamin B 12 cutoff point used. A recent study showed a prevalence of true deficiency of 32.7% based on measuring both serum vitamin B 12 level and plasma methylmalonic acid. (authors).

  6. Is vitamin B12 deficiency a risk factor for cardiovascular disease in vegetarians?

    Science.gov (United States)

    Pawlak, Roman

    2015-06-01

    The goal of this paper is to describe the role of vitamin B12 deficiency in cardiovascular disease development among vegetarians. Vegetarians have a high prevalence of vitamin B12 deficiency. Deficiency of this vitamin is associated with a variety of atherogenic processes that are mainly, but not exclusively, due to vitamin B12 deficiency-induced hyperhomocysteinemia. Each 5-μmol/L increase above 10 μmol/L of serum homocysteine is associated with a 20% increased risk of circulatory health problems. Mean homocysteine concentration >10 μmol/L among vegetarians was reported in 32 of 34 reports. Macrocytosis associated with vitamin B12 deficiency is also associated with fatal and non-fatal coronary disease, myocardial infarction, stroke, and other circulatory health problems. Compared with non-vegetarians, vegetarians have an improved profile of the traditional cardiovascular disease risk factors, including serum lipids, blood pressure, serum glucose concentration, and weight status. However, not all studies that assessed cardiovascular disease incidence among vegetarians reported a protective effect. Among studies that did show a lower prevalence of circulatory health problems, the effect was not as pronounced as expected, which may be a result of poor vitamin B12 status due to a vegetarian diet. Vitamin B12 deficiency may negate the cardiovascular disease prevention benefits of vegetarian diets. In order to further reduce the risk of cardiovascular disease, vegetarians should be advised to use vitamin B12 supplements. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  7. Mathematical modeling of glutathione status in type 2 diabetics with vitamin B12 deficiency

    Directory of Open Access Journals (Sweden)

    Varun eKaramshetty

    2016-03-01

    Full Text Available Deficiencies in vitamin B12 and glutathione (GSH are associated with anumber of diseases including type 2 diabetes mellitus. We tested newly diag-nosed Indian diabetic patients for correlation between their vitamin B12 andGSH, and found it to be weak. Here we seek to examine the theoreticaldependence of GSH on vitamin B12 with a mathematical model of 1-carbonmetabolism due to Reed and co-workers. We study the methionine cycleof the Reed-Nijhout model by developing a simple ‘stylized model’ that cap-tures its essential topology and whose kinetics are analytically tractable. Theanalysis shows – somewhat counter-intuitively – that the flux responsible forthe homeostasis of homocysteine is, in fact, peripheral to the methioninecycle. Elevation of homocysteine arises from reduced activity of methioninesynthase, a vitamin B12-dependent enzyme, however, this does not increaseGSH biosynthesis. The model suggests that the lack of vitamin B12–GSHcorrelation is explained by suppression of activity in the trans-sulfurationpathway that limits the synthesis of cysteine and GSH from homocysteine.We hypothesize this ‘cysteine-block’ is an essential consequence of vitaminB12 deficiency. It can be clinically relevant to appreciate that these secondaryeffects of vitamin B12 deficiency could be central to its pathophysiology.

  8. Measurement of FA and VitB12 in serum by TRFIA and its clinical application

    International Nuclear Information System (INIS)

    Zhou Jinhong; Wang Huimin

    2006-01-01

    To investigate the correlation between diseases and the quantity of folic acid(FA) and vitamine B 12 (VitB 12 ) in serum, the quantity of FA and VitB 12 in serum was measured by TR- FIA. The results showed that the levels of FA and VitB 12 in 68 controlled subjects were 20.13±5.72 nmol/L and 240.45±58.23 pmol/L respectively. The levels of FA and VitB 12 in 6 patients with megaloblastic anemia, 26 with medium-terminal gestation femineity, 7 with liver cirrhosis, 10 with gastric ulcerand 31 with cerebral infarction were significant lower than those in the control group. The level of FA in 24 with malignant hematopathy and 57 with malignant tumor was significantly lower but VitB 12 between the 31 patients with iron deficiency anemia and 12 with CAA and the control group. The amount of the FA in 9 patients with chronic atrophic gastritis and 42 blood donors were lower than that in the control. The determination of FA and VitB 12 levels may be quite significant in the diagnosis, therapy and prognosis of diseases. Laboratories should establish the reference values which fit the locals specifically. (authors)

  9. High vitamin B12 level and good treatment outcome may be associated in major depressive disorder

    Directory of Open Access Journals (Sweden)

    Tanskanen Antti

    2003-12-01

    Full Text Available Abstract Background Despite of an increasing body of research the associations between vitamin B12 and folate levels and the treatment outcome in depressive disorders are still unsolved. We therefore conducted this naturalistic prospective follow-up study. Our aim was to determine whether there were any associations between the vitamin B12 and folate level and the six-month treatment outcome in patients with major depressive disorder. Because vitamin B12 and folate deficiency may result in changes in haematological indices, including mean corpuscular volume, red blood cell count and hematocrit, we also examined whether these indices were associated with the treatment outcome. Methods Haematological indices, erythrocyte folate and serum vitamin B12 levels were determined in 115 outpatients with DSM-III-R major depressive disorder at baseline and serum vitamin B12 level again on six-month follow-up. The 17-item Hamilton Depression Rating Scale was also compiled, respectively. In the statistical analysis we used chi-squared test, Pearson's correlation coefficient, the Student's t-test, analysis of variance (ANOVA, and univariate and multivariate linear regression analysis. Results Higher vitamin B12 levels significantly associated with a better outcome. The association between the folate level and treatment outcome was weak and probably not independent. No relationship was found between haematological indices and the six-month outcome. Conclusion The vitamin B12 level and the probability of recovery from major depression may be positively associated. Nevertheless, further studies are suggested to confirm this finding.

  10. Combined vitamin B-12 and balanced protein-energy supplementation affect homocysteine remethylation in the methionine cycle in pregnant south Indian women of low vitamin B-12 status

    Science.gov (United States)

    Low-quality dietary protein intake and vitamin B-12 deficiency could interact to decrease methionine transmethylation and remethylation rates during pregnancy, and may affect epigenetic modifications of the fetal genome. The objective of this randomized, partially open-labeled intervention trial was...

  11. Bread cofortified with folic acid and vitamin B-12 improves the folate and vitamin B-12 status of healthy older people: a randomized controlled trial

    NARCIS (Netherlands)

    Winkels, R.M.; Brouwer, I.A.; Clarke, R.; Katan, M.B.; Verhoef, P.

    2008-01-01

    Background: Mandatory fortification of flour with folic acid has reduced the number of neural tube defects in North America. Concerns that high intakes of folic acid might mask vitamin B-12 deficiency in older persons have delayed the introduction of fortification in many European countries.

  12. Vitamin B(12) dependent changes in mouse spinal cord expression of vitamin B(12) related proteins and the epidermal growth factor system

    DEFF Research Database (Denmark)

    Mutti, Elena; Lildballe, Dorte L; Kristensen, Lise

    2013-01-01

    Chronic vitamin B(12) (cobalamin) deficiency in the mammalian central nervous system causes degenerative damage, especially in the spinal cord. Previous studies have shown that cobalamin status alters spinal cord expression of epidermal growth factor (EGF) and its receptor in rats. Employing...

  13. Prediction of site-specific interactions in antibody-antigen complexes: the proABC method and server.

    KAUST Repository

    Olimpieri, Pier Paolo

    2013-06-26

    MOTIVATION: Antibodies or immunoglobulins are proteins of paramount importance in the immune system. They are extremely relevant as diagnostic, biotechnological and therapeutic tools. Their modular structure makes it easy to re-engineer them for specific purposes. Short of undergoing a trial and error process, these experiments, as well as others, need to rely on an understanding of the specific determinants of the antibody binding mode. RESULTS: In this article, we present a method to identify, on the basis of the antibody sequence alone, which residues of an antibody directly interact with its cognate antigen. The method, based on the random forest automatic learning techniques, reaches a recall and specificity as high as 80% and is implemented as a free and easy-to-use server, named prediction of Antibody Contacts. We believe that it can be of great help in re-design experiments as well as a guide for molecular docking experiments. The results that we obtained also allowed us to dissect which features of the antibody sequence contribute most to the involvement of specific residues in binding to the antigen. AVAILABILITY: http://www.biocomputing.it/proABC. CONTACT: anna.tramontano@uniroma1.it or paolo.marcatili@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

  14. Vitamin B12: unique metalorganic compounds and the most complex vitamins.

    Science.gov (United States)

    Randaccio, Lucio; Geremia, Silvano; Demitri, Nicola; Wuerges, Jochen

    2010-04-30

    The chemistry and biochemistry of the vitamin B(12) compounds (cobalamins, XCbl) are described, with particular emphasis on their structural aspects and their relationships with properties and function. A brief history of B(12), reveals how much the effort of chemists, biochemists and crystallographers have contributed in the past to understand the basic properties of this very complex vitamin. The properties of the two cobalamins, the two important B(12) cofactors Ado- and MeCbl are described, with particular emphasis on how the Co-C bond cleavage is involved in the enzymatic mechanisms. The main structural features of cobalamins are described, with particular reference to the axial fragment. The structure/property relationships in cobalamins are summarized. The recent studies on base-off/base-on equilibrium are emphasized for their relevance to the mode of binding of the cofactor to the protein scaffold. The absorption, transport and cellular uptake of cobalamins and the structure of the B(12) transport proteins, IF and TC, in mammals are reviewed. The B(12) transport in bacteria and the structure of the so far determined proteins are briefly described. The currently accepted mechanisms for the catalytic cycles of the AdoCbl and MeCbl enzymes are reported. The structure and function of B(12) enzymes, particularly the important mammalian enzymes methyltransferase (MetH) and methyl-malonyl-coenzyme A mutase (MMCM), are described and briefly discussed. Since fast proliferating cells require higher amount of vitamin B(12) than that required by normal cells, the study of B(12 )conjugates as targeting agents has recently gained importance. Bioconjugates have been studied as potential agents for delivering radioisotopes and NMR probes or as various cytotoxic agents towards cancer cells in humans and the most recent studies are described. Specifically, functionalized bioconjugates are used as "Trojan horses" to carry into the cell the appropriate antitumour or diagnostic

  15. Vitamin B12: Unique Metalorganic Compounds and the Most Complex Vitamins

    Directory of Open Access Journals (Sweden)

    Lucio Randaccio

    2010-04-01

    Full Text Available The chemistry and biochemistry of the vitamin B12 compounds (cobalamins, XCbl are described, with particular emphasis on their structural aspects and their relationships with properties and function. A brief history of B12, reveals how much the effort of chemists, biochemists and crystallographers have contributed in the past to understand the basic properties of this very complex vitamin. The properties of the two cobalamins, the two important B12 cofactors Ado- and MeCbl are described, with particular emphasis on how the Co-C bond cleavage is involved in the enzymatic mechanisms. The main structural features of cobalamins are described, with particular reference to the axial fragment. The structure/property relationships in cobalamins are summarized. The recent studies on base-off/base-on equilibrium are emphasized for their relevance to the mode of binding of the cofactor to the protein scaffold. The absorption, transport and cellular uptake of cobalamins and the structure of the B12 transport proteins, IF and TC, in mammals are reviewed. The B12 transport in bacteria and the structure of the so far determined proteins are briefly described. The currently accepted mechanisms for the catalytic cycles of the AdoCbl and MeCbl enzymes are reported. The structure and function of B12 enzymes, particularly the important mammalian enzymes methyltransferase (MetH and methyl-malonyl-coenzymeA mutase (MMCM, are described and briefly discussed. Since fast proliferating cells require higher amount of vitamin B12 than that required by normal cells, the study of B12 conjugates as targeting agents has recently gained importance. Bioconjugates have been studied as potential agents for delivering radioisotopes and NMR probes or as various cytotoxic agents towards cancer cells in humans and the most recent studies are described. Specifically, functionalized bioconjugates are used as “Trojan horses” to carry into the cell the appropriate antitumour or

  16. Smoking Discriminately Changes the Serum Active and Non-Active Forms of Vitamin B12

    Directory of Open Access Journals (Sweden)

    Niloofar Shekoohi

    2017-08-01

    Full Text Available Smoking may modify the appetite, and consequently affect nutrient intake and serum micronutrients. The effect of smoking on vitamin B12 status has been considered in several studies. The research proposed that organic nitrites, nitro oxide, cyanides, and isocyanides of cigarette smoke interfere with vitamin B12 metabolism, and convert it to inactive forms. This research was carried out to determine the serum level of active and inactive forms of vitamin B12 in male smokers in comparison with male nonsmokers. This is a case-control study, in which the participants were 85 male smokers and 85 male nonsmokers. The serum levels of total and active form of vitamin B12 were measured. Dietary intake was recorded by a quantitative food frequency questionnaire and one-day 24-hour dietary recall method. Independent two sample T test was used to compare quantitative variables between the case and control groups. The serum level of total vitamin B12 was not significantly different between two groups, but serum level of active form of vitamin B12 in the smoking group was significantly lower than non-smoking group (P<0.001. This is one of the first studies that evaluated the serum level of active form of vitamin B12 in smokers in the Iranian community. The results of this study identified that serum level of total vitamin B12 might be not different between smoking and non-smoking people, but the function of this vitamin is disturbed in the body of smokers through the reduction of serum level of active form of vitamin B12.

  17. High Prevalence of Vitamin B12 Deficiency and No Folate Deficiency in Young Children in Nepal

    Directory of Open Access Journals (Sweden)

    Bernadette N. Ng’eno

    2017-01-01

    Full Text Available Many children in low- and middle-income countries may have inadequate intake of vitamin B12 and folate; data confirming these inadequacies are limited. We used biochemical, demographic, behavioral and anthropometric data to describe the folate and vitamin B12 concentrations among six- to 23-month-old Nepalese children. Vitamin B12 (serum B12 < 150 pmol/L and folate deficiencies (red blood cell (RBC folate < 226.5 nmol/L were assessed. We used logistic regression to identify predictors of vitamin B12 deficiency. The vitamin B12 geometric mean was 186 pmol/L; 30.2% of children were deficient. The mean RBC folate concentration was 13,612 nmol/L; there was no deficiency. Factors associated with vitamin B12 deficiency included: (a age six to 11 months (adjusted odds ratio (aOR 1.51; 95% confidence interval (CI: 1.18, 1.92 or 12–17 months (aOR 1.38; 95% CI: 1.10, 1.72 compared to 18–23 months; (b being stunted (aOR 1.24; 95% CI: 1.03, 1.50 compared to not being stunted; (c and not eating animal-source foods (aOR 1.85; 95% CI: 1.42, 2.41 compared to eating animal-source foods the previous day. There was a high prevalence of vitamin B12 deficiency, but no folate deficiency. Improving early feeding practices, including the consumption of rich sources of vitamin B12, such as animal-source foods and fortified foods, may help decrease deficiency.

  18. Therapeutic role of Vitamin B12 in patients of chronic tinnitus: A pilot study

    Directory of Open Access Journals (Sweden)

    Charu Singh

    2016-01-01

    Full Text Available True tinnitus is a phantom auditory perception arising from a source or trigger in the cochlea, brainstem, or at higher centers and has no detectable acoustic generator. The most accepted is the famous neurophysiologic model of Jastreboff, which stresses that tinnitus, is a subcortical perception and results from the processing of weak neural activity in the periphery. The aim of this study is to determine the role of Vitamin B12 in treatment of chronic tinnitus. In this randomized, double-blind pilot study, total 40 patients were enrolled, of which 20 in Group A (cases received intramuscular therapy of 1 ml Vitamin B12 (2500 mcg weekly for a period of 6 weeks and Group B (20 patients received placebo isotonic saline 01 ml intramuscular. The patients were subjected to Vitamin B12 assay and audiometry pre- and post-therapy. Of the total patients of tinnitus, 17 were Vitamin B12 deficient that is 42.5% showed deficiency when the normal levels were considered to be 250 pg/ml. A paired t-test showed that in Group A, patients with Vitamin B12 deficiency showed significant improvement in mean tinnitus severity index score and visual analog scale (VAS after Vitamin B12 therapy. This pilot study highlights the significant prevalence of Vitamin B12 deficiency in North Indian population and improvement in tinnitus severity scores and VAS in cobalamin-deficient patients receiving intramuscular Vitamin B12 weekly for 6 weeks further provides a link between cobalamin deficiency and tinnitus thereby suggestive of a therapeutic role of B12 in cobalamin-deficient patients of tinnitus.

  19. Therapeutic role of Vitamin B12 in patients of chronic tinnitus: A pilot study.

    Science.gov (United States)

    Singh, Charu; Kawatra, Rahul; Gupta, Jaya; Awasthi, Vishnu; Dungana, Homnath

    2016-01-01

    True tinnitus is a phantom auditory perception arising from a source or trigger in the cochlea, brainstem, or at higher centers and has no detectable acoustic generator. The most accepted is the famous neurophysiologic model of Jastreboff, which stresses that tinnitus, is a subcortical perception and results from the processing of weak neural activity in the periphery. The aim of this study is to determine the role of Vitamin B12 in treatment of chronic tinnitus. In this randomized, double-blind pilot study, total 40 patients were enrolled, of which 20 in Group A (cases) received intramuscular therapy of 1 ml Vitamin B12 (2500 mcg) weekly for a period of 6 weeks and Group B (20) patients received placebo isotonic saline 01 ml intramuscular. The patients were subjected to Vitamin B12 assay and audiometry pre- and post-therapy. Of the total patients of tinnitus, 17 were Vitamin B12 deficient that is 42.5% showed deficiency when the normal levels were considered to be 250 pg/ml. A paired t-test showed that in Group A, patients with Vitamin B12 deficiency showed significant improvement in mean tinnitus severity index score and visual analog scale (VAS) after Vitamin B12 therapy. This pilot study highlights the significant prevalence of Vitamin B12 deficiency in North Indian population and improvement in tinnitus severity scores and VAS in cobalamin-deficient patients receiving intramuscular Vitamin B12 weekly for 6 weeks further provides a link between cobalamin deficiency and tinnitus thereby suggestive of a therapeutic role of B12 in cobalamin-deficient patients of tinnitus.

  20. Subacute combined spinal cord degeneration and pancytopenia secondary to severe vitamin B12 deficiency

    Directory of Open Access Journals (Sweden)

    José Luis Cabrerizo-García

    Full Text Available CONTEXT: Decreased vitamin B12 concentration does not usually result in clinical or hematological abnormalities. Subacute combined spinal cord degeneration and pancytopenia are two serious and rarely displayed consequences that appear in severe deficits. CASE REPORT: We present the case of a patient with subacute combined spinal cord degeneration and pancytopenia secondary to severe and sustained vitamin B12 deficiency. Such cases are rare nowadays and have potentially fatal consequences. CONCLUSIONS: Vitamin B12 deficiency should be taken into consideration in the differential diagnosis in cases of blood disorders or severe neurological symptoms. Early diagnosis and treatment can avoid irreversible consequences.

  1. Vitamin B-12 concentration, memory performance, and hippocampal structure in patients with mild cognitive impairment.

    Science.gov (United States)

    Köbe, Theresa; Witte, A Veronica; Schnelle, Ariane; Grittner, Ulrike; Tesky, Valentina A; Pantel, Johannes; Schuchardt, Jan Philipp; Hahn, Andreas; Bohlken, Jens; Rujescu, Dan; Flöel, Agnes

    2016-04-01

    Low-normal concentrations of vitamin B-12 (VitB12) may be associated with worse cognition. However, previous evidence has been mixed, and the underlying mechanisms remain unclear. We determined whether serum VitB12 concentrations within the normal range were linked to memory functions and related neuronal structures in patients with mild cognitive impairment (MCI). In a cross-sectional design, we assessed 100 amnestic MCI patients (52 women; age range: 50-80 y) with low- and high-normal VitB12 concentration (median split: 304 pmol/L) for memory functions with the use of the Auditory Verbal Learning Test. MRI was performed at 3 tesla (n= 86) for the estimation of the volume and microstructure of the hippocampus and its subfields as indicated by the mean diffusivity on diffusion-weighted images. With the use of a mediation analysis, we examined whether the relation between VitB12 and memory performance was partially explained by volume or microstructure. MCI patients with low-normal VitB12 showed a significantly poorer learning ability (P= 0.014) and recognition performance (P= 0.008) than did patients with high-normal VitB12. Also, the microstructure integrity of the hippocampus was lower in patients with low-normal VitB12, mainly in the cornu ammonis 4 and dentate gyrus region (P= 0.029), which partially mediated the effect of VitB12 on memory performance (32-48%). Adjustments for age, sex, education, apolipoprotein E e4 status, and total homocysteine, folate, and creatinine did not attenuate the effects. Low VitB12 concentrations within the normal range are associated with poorer memory performance, which is an effect that is partially mediated by the reduced microstructural integrity of the hippocampus. Future interventional trials are needed to assess whether supplementation of VitB12 may improve cognition in MCI patients even in the absence of clinically manifested VitB12 deficiency. This trial was registered at clinicaltrials.gov as NCT01219244. © 2016

  2. Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets

    DEFF Research Database (Denmark)

    Grarup, Niels; Sulem, Patrick; Sandholt, Camilla H

    2013-01-01

    of the underlying biology of human traits and diseases. Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architecture of serum levels of vitamin B12 (B12) and folate. Up to 22.9 million sequence variants were analyzed in combined...... in serum B12 or folate levels do not modify the risk of developing these conditions. Yet, the study demonstrates the value of combining whole genome and exome sequencing approaches to ascertain the genetic and molecular architectures underlying quantitative trait associations....

  3. Demencia por déficit de vitamina B12: reporte de caso

    OpenAIRE

    Junco Bonet, Miguel Damián

    2014-01-01

    Fundamento: la deficiencia de vitamina B12 (cianocobalamina) puede producir varios desórdenes neurológicos, incluida la neuropatía periférica, degeneración subaguda combinada de la médula espinal, neuropatía óptica y alteraciones cognitivas que van desde la confusión leve hasta la demencia o la psicosis. La causa más frecuente de deficiencia de vitamina B12 es la anemia perniciosa. Objetivo: presentar un caso clínico de demencia por déficit de vitamina B12. Caso clínico: paciente masculino de...

  4. Structural basis of nanobody-mediated blocking of BtuF, the cognate substrate-binding protein of the Escherichia coli vitamin B12 transporter BtuCD.

    Science.gov (United States)

    Mireku, S A; Sauer, M M; Glockshuber, R; Locher, K P

    2017-10-30

    Bacterial ABC importers catalyze the uptake of essential nutrients including transition metals and metal-containing co-factors. Recently, an IgG antibody targeting the external binding protein of the Staphylococcus aureus Mn(II) ABC importer was reported to inhibit transport activity and reduce bacterial cell growth. We here explored the possibility of using alpaca-derived nanobodies to inhibit the vitamin B12 transporter of Escherichia coli, BtuCD-F, as a model system by generating nanobodies against the periplasmic binding protein BtuF. We isolated six nanobodies that competed with B12 for binding to BtuF, with inhibition constants between 10 -6 and 10 -9  M. Kinetic characterization of the nanobody-BtuF interactions revealed dissociation half-lives between 1.6 and 6 minutes and fast association rates between 10 4 and 10 6  M -1 s -1 . For the tightest-binding nanobody, we observed a reduction of in vitro transport activity of BtuCD-F when an excess of nanobody over B12 was used. The structure of BtuF in complex with the most effective nanobody Nb9 revealed the molecular basis of its inhibitory function. The CDR3 loop of Nb9 reached into the substrate-binding pocket of BtuF, preventing both B12 binding and BtuCD-F complex formation. Our results suggest that nanobodies can mediate ABC importer inhibition, providing an opportunity for novel antibiotic strategies.

  5. Genetic signatures in the envelope glycoproteins of HIV-1 that associate with broadly neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    S Gnanakaran

    Full Text Available A steady increase in knowledge of the molecular and antigenic structure of the gp120 and gp41 HIV-1 envelope glycoproteins (Env is yielding important new insights for vaccine design, but it has been difficult to translate this information to an immunogen that elicits broadly neutralizing antibodies. To help bridge this gap, we used phylogenetically corrected statistical methods to identify amino acid signature patterns in Envs derived from people who have made potently neutralizing antibodies, with the hypothesis that these Envs may share common features that would be useful for incorporation in a vaccine immunogen. Before attempting this, essentially as a control, we explored the utility of our computational methods for defining signatures of complex neutralization phenotypes by analyzing Env sequences from 251 clonal viruses that were differentially sensitive to neutralization by the well-characterized gp120-specific monoclonal antibody, b12. We identified ten b12-neutralization signatures, including seven either in the b12-binding surface of gp120 or in the V2 region of gp120 that have been previously shown to impact b12 sensitivity. A simple algorithm based on the b12 signature pattern was predictive of b12 sensitivity/resistance in an additional blinded panel of 57 viruses. Upon obtaining these reassuring outcomes, we went on to apply these same computational methods to define signature patterns in Env from HIV-1 infected individuals who had potent, broadly neutralizing responses. We analyzed a checkerboard-style neutralization dataset with sera from 69 HIV-1-infected individuals tested against a panel of 25 different Envs. Distinct clusters of sera with high and low neutralization potencies were identified. Six signature positions in Env sequences obtained from the 69 samples were found to be strongly associated with either the high or low potency responses. Five sites were in the CD4-induced coreceptor binding site of gp120, suggesting an

  6. Relationship between soil cobalt and vitamin B12 levels in the liver ...

    African Journals Online (AJOL)

    Materlais and methods: Liver and muscle tissues of livestock grazing on the selected areas were analyzed for the content ... Keywords: Soil, vitamin B12, cobalt, cattle, uptake, transfer ..... Krajcovicova-Kudlackova M, Blazicek P, Babinska K,.

  7. Svaer vitamin B12-mangel hos spaedbørn brysternaeret af veganere

    DEFF Research Database (Denmark)

    Roed, Casper; Skovby, Flemming; Lund, Allan Meldgaard

    2009-01-01

    Weight loss and reduction of motor skills resulted in paediatric evaluation of a 10-month-old girl and a 12-month-old boy. Both children suffered form anaemia and delayed development due to vitamin B12 deficiency caused by strict maternal vegan diet during pregnancy and nursing. Therapy with cyan......Weight loss and reduction of motor skills resulted in paediatric evaluation of a 10-month-old girl and a 12-month-old boy. Both children suffered form anaemia and delayed development due to vitamin B12 deficiency caused by strict maternal vegan diet during pregnancy and nursing. Therapy...... with cyanocobalamin was instituted with remission of symptoms. Since infants risk irreversible neurologic damage following severe vitamin B12 deficiency, early diagnosis and treatment are mandatory. Vegan and vegetarian women should take vitamin B12 supplementation during the pregnancy and nursing period...

  8. Relation between serum vitamin B12 level and duration of treatment with carbamazepine in epilepsy patients

    Directory of Open Access Journals (Sweden)

    Mohammad Tariqul Islam

    2016-12-01

    Full Text Available Vitamin B12 levels in the serum of 58 epileptic patients receiving only carbamazepine for at least 6 months were measured. Same number of epilepsy patients with no history of taking antiepileptic medicine were taken as control. The mean level of vitamin B12 in carbamazepine-treated epileptic patients was 265.5 pg/mL whereas it was 478.3 pg/mL in control. Increased duration of treatment of carbamazepine in epilepsy caused significantly decreased level of serum vitamin B12 (Pearson correlation coefficient, r = -0.9, p<0.0001. In conclusion, serum vitamin B12 level significantly decreased in relation to duration of carbamazepine treatment in epileptic patients.

  9. Vitamin B12 Deficiency in Persons with Intellectual Disability in a Vegetarian Residential Care Community

    Directory of Open Access Journals (Sweden)

    Mohammed Morad

    2005-01-01

    Full Text Available The goal of this study was to determine the prevalence of vitamin B12 deficiency among intellectually disabled persons in a vegetarian remedial community in Israel. In this community, 47 individuals with intellectual disability (ID live in 7 enlarged families in a kibbutz style agricultural setting. These 47 individuals and 17 of their caregivers were screened for vitamin B12 deficiency. There were 25.5% of the disabled vs. 11.8% of the caregivers found to have levels of vitamin B12 lower than 157 pg/ml. It is concluded that persons with ID in this vegetarian residential care community seemed to be at a higher risk for vitamin B12 deficiency.

  10. Absorption and transport of radioactive 57Co-vitamin B12 in experimental giardiasis in rats

    International Nuclear Information System (INIS)

    Deka, N.C.; Sehgal, A.K.; Chnuttani, P.N.

    1981-01-01

    Giardiasis was produced in weanling albino rats by feeding suspension of Giardia lamblia cysts isolated from human stool. Experiments were carried out to assess the absorption and transport through intestinal wall of 57 Co-vitamin B 12 in these rats. The results showed a significant impairment of the absorption of the vitamin in the rats with experimental giardiasis. However, the transport of the vitamin B 12 was unimpaired. (author)

  11. Study of Methionine, Vitamin B12, and Folic Acid Status in Coronary Atherosclerotic Male Patients

    OpenAIRE

    M Djalali; SR A Hoseiny; F Siassi; N Fardad; R Ghiasvand; TR Neyestani

    2007-01-01

    Background: Increased level of serum homocysteine is one of the risk factor of atherosclerosis. Its production related in some sulfur amino acids such as methionine. Some important cofactors that are involved in metabolic pathways of this amino acid are folate and vitamin B12. We have assessed the status of methionine, folic acid, and vitamin B12 in some coronary atherosclerotic male patients.Methods: In this case-control study, 46 cases of coronary atherosclerosis were selected from male pat...

  12. Vitamin B12 deficiency is associated with geographical latitude and solar radiation in the older population.

    Science.gov (United States)

    Cabrera, Sebastián; Benavente, David; Alvo, Miriam; de Pablo, Paola; Ferro, Charles J

    2014-11-01

    Vitamin B12 and folic acid deficiency are common in the older and are associated with several conditions including anaemia, cardiovascular disease, cognitive impairment and cancer. Evidence from in vitro studies suggests that solar radiation can degrade both vitamins in the skin. Chile is the longest country in the world running perfectly North-South making it an ideal place to study potential associations of latitude and solar radiation on vitamin B12 and folic acid deficiency. The objective was to examine the association between vitamin B12 and folic acid deficiencies and latitude. Plasma samples were collected from Chileans aged 65+ years (n=1013) living across the whole country and assayed for vitamin B12 and folic acid concentrations as part of the Chilean Health Survey 2009-2010, which is a national representative sample study. Overall, the prevalence of vitamin B12 deficiency was 11.3%, with the prevalence in the North of the country being significantly greater than in the Central and South zones (19.1%,10.5%, and 5.7%, respectively; Psolar radiation (OR 1.203 [95% confidence intervals 1.119-1.294], Psolar radiation. Although degradation by solar radiation might explain this observation, further work is required to establish the potential mechanisms. In countries that routinely fortify food with folic acid, efforts to identify vitamin B12 deficiency might be more cost-efficiently targeted in areas closest to the Equator. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Serum Homocysteine, Vitamin B12, Folic Acid Levels and Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphism in Vitiligo

    Science.gov (United States)

    Yasar, Ali; Gunduz, Kamer; Onur, Ece; Calkan, Mehmet

    2012-01-01

    The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo. PMID:22846211

  14. Serum Homocysteine, Vitamin B12, Folic Acid Levels and Methylenetetrahydrofolate Reductase (MTHFR Gene Polymorphism in Vitiligo

    Directory of Open Access Journals (Sweden)

    Ali Yasar

    2012-01-01

    Full Text Available The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy levels as well as MTHFR (C677, A1298C gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C do not seem to create susceptibility for vitiligo.

  15. Validity of transcobalamin II-based radioassay for the determination of serum vitamin B12 concentrations

    International Nuclear Information System (INIS)

    Paltridge, G.; Rudzki, Z.; Ryall, R.G.

    1980-01-01

    A valid radioassay for the estimation of serum vitamin B 12 in the presence of naturally occurring vitamin B 12 (= cobalamin) analogues can be operated if serum transcobalamin II (TC II) is used as the binding protein. Serum samples that gave diagnostically discrepant results when their vitamin B 12 content was analysed (i) by a commercial radioassay known to be susceptible to interference from cobalamin analogues, and (ii) by microbiological assay, were further analysed by an alternative radioassay which uses the transcobalamins (principally TC II) of diluted normal serum as the assay binding protein. Concordance between the results from microbiological assay and the TC II-based radioassay was found in all cases. In an extended study over a three-year period, all routine serum samples sent for vitamin B 12 analysis that had a vitamin B 12 content of less than 320 ng/l by the TC II-based radioassay (reference range 200-850 ng/l) were reanalysed using an established microbiological method. Over 1000 samples were thus analysed. The data are presented to demonstrate the validity of the TC II-based radioassay results in this group of patients, serum samples from which are most likely to produce diagnostically erroneous vitamin B 12 results when analysed by a radioassay that is less specific for cobalamins. (author)

  16. Vitamin B12 deficiency is associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hansen, Christian S; Jensen, Jan S; Ridderstråle, Martin

    2017-01-01

    .01; 0.43, p=0.038), and a decrease in 5min RHR of 0.25 beats per minute (95% CI -0.47; -0.03, p=0.025). CONCLUSION: Vitamin B12 may be inversely associated with CAN in patients with type 2 diabetes. Confirmatory studies investigating a causal role of vitamin B12 for the development of diabetic CAN......AIMS: Vitamin B12 deficiency could be associated with cardiovascular autonomic neuropathy (CAN) in diabetes patients. We aim to investigate the association between serum levels of vitamin B12 and CAN in type 2 diabetes patients. METHODS: 469 ambulatory type 2 diabetes patients (mean diabetes...... duration 10.0years (IQR 5.0;17.0), mean age 59.0years (SD 11.6), 63% men, mean B12 289.0pmol/l (IQR 217;390)) were screened for CAN using three cardiovascular reflex tests, five minute resting heart rate (5min RHR) and heart rate variability indices. RESULTS: Serum levels of vitamin B12 were significantly...

  17. Beneficial effect of antibodies against β- secretase cleavage site of APP on Alzheimer's-like pathology in triple-transgenic mice.

    Directory of Open Access Journals (Sweden)

    Inna Rabinovich-Nikitin

    Full Text Available The toxicity of amyloid β and tau, the two hallmark proteins in Alzheimer's disease (AD, has been extensively studied individually. Recently new data suggest their possible interactions and synergistic effects in the disease. In this study, we investigate the ability of antibodies against the β secretase cleavage site on APP, named BBS1, to affect tau pathology, besides their well established effect on intracellular Aβ and amyloid load. For this purpose we treated the triple transgenic mice model of AD (3x Tg-AD with mAb BBS1 intracerebroventricularly, using mini osmotic pumps for one month. The experimental data demonstrated reduction in total and phosphorylated tau levels, explained by significant reduction in GSK3β which phosphorylates tau on sites recognized by antibodies against PHF1 and AT-8. The treatment increased the cognitive capabilities and reduced the brain inflammation levels which accompany AD pathology. The data showing that tau pathology was significantly reduced by BBS1 antibodies suggest a close interaction between tau and Aβ in the development of AD, and may serve as an efficient novel immunotherapy against both hallmarks of this disease.

  18. A first-principles study on the adsorption behavior of amphetamine on pristine, P- and Al-doped B12N12 nano-cages

    Science.gov (United States)

    Bahrami, Aidin; Seidi, Shahram; Baheri, Tahmineh; Aghamohammadi, Mohammad

    2013-12-01

    The first-principles computations using density functional theory (DFT) calculations at the M062X/6-311++G** level have been applied to scrutinize the adsorption behavior of amphetamine (AMP) molecule on the external surface of pristine, P- and Al-doped B12N12 nano-cages. In order to gain insight into the binding features of pristine and doped B12N12 complexes as adsorbent with AMP, the structural and electronic parameters as well as the Atoms in Molecules (AIM) properties were examined. The results showed that AMP prefers to adsorb via its nitrogen atom on the Lewis acid sites of B and Al atoms of the nano-cages. On the basis of calculated density of states, the interaction of AMP with the external wall of B12N12 leads to the remarkable differences in their conductivities. Presence of polar solvent increases the AMP adsorption on the nano-cage. In addition, AIM based analyses indicated an electrostatic nature for N-B interaction in Amph-B12N12 and partial covalent for N-Al in AMP-B11AlN12. Based on calculated results, the B12N12 and B11AlN12 nano-cages are expected to be a potential efficient adsorbent as well as sensors for adsorption of AMP in environmental systems.

  19. A remote arene-binding site on prostate specific membrane antigen revealed by antibody-recruiting small molecules

    Czech Academy of Sciences Publication Activity Database

    Zhang, A.X.; Murelli, R.P.; Bařinka, Cyril; Michel, J.; Cocleaza, A.; Jorgensen, W.L.; Lubkowski, J.; Spiegel, D.A.

    2010-01-01

    Roč. 132, č. 36 (2010), s. 12711-12716 ISSN 0002-7863 Institutional research plan: CEZ:AV0Z50520701 Keywords : Prostate -specific membrane antigen * antibody recruiting molecules * Structure-activity relationship Subject RIV: CE - Biochemistry Impact factor: 9.019, year: 2010

  20. The original Pathologische Anatomie Leiden-Endothelium monoclonal antibody recognizes a vascular endothelial growth factor binding site within neuropilin-1

    NARCIS (Netherlands)

    Jaalouk, Diana E.; Ozawa, Nfichael G.; Sun, Jessica; Lahdenranta, Johanna; Schlingemann, Reinier O.; Pasqualini, Renata; Arap, Wadih

    2007-01-01

    For two decades, the antigen recognized by the Pathologische Anatomie Leiden-Endothelium (PAL-E) monoclonal antibody, a standard vascular endothelial cell marker, has remained elusive. Here, we used a combinatorial phage display-based approach ("epitope mapping") to select peptides binding to the

  1. Antigenic sites on the HN domain of botulinum neurotoxin A stimulate protective antibody responses against active toxin.

    Science.gov (United States)

    Ayyar, B Vijayalakshmi; Tajhya, Rajeev B; Beeton, Christine; Atassi, M Zouhair

    2015-10-28

    Botulinum neurotoxins (BoNTs) are the most toxic substances known. BoNT intoxicates cells in a highly programmed fashion initiated by binding to the cell surface, internalization and enzymatic cleavage of substrate, thus, inhibiting synaptic exocytosis. Over the past two decades, immunological significance of BoNT/A C-terminal heavy chain (HC) and light chain (LC) domains were investigated extensively leading to important findings. In the current work, we explored the significance of BoNT/A heavy chain N-terminal (HN) region as a vaccine candidate. Mice were immunized with recombinant HN519-845 generating antibodies (Abs) that were found to be protective against lethal dose of BoNT/A. Immuno-dominant regions of HN519-845 were identified and individually investigated for antibody response along with synthetic peptides within those regions, using in vivo protection assays against BoNT/A. Results were confirmed by patch-clamp analysis where anti-HN antibodies were studied for the ability to block toxin-induced channel formation. This data strongly indicated that HN519-593 is an important region in generating protective antibodies and should be valuable in a vaccine design. These results are the first to describe and dissect the protective activity of the BoNT/A HN domain.

  2. Relationship among plasma vitamin B12 and folic acid levels and coronary artery disease

    Directory of Open Access Journals (Sweden)

    Masoomeh Tohidhi

    2012-04-01

    Full Text Available Background: Hyperhomocysteinemia is a new risk factor for cardiovascular disease. It is a sensitive marker of the vitamin B12 and folate insufficiency. Folate and vitamin B12 may be a protective effect on cardiovascular disease. According to limited data about role of vitamin B12 and folate in coronary artery disease (CAD, we conducted this study to measure these factors in patients with coronary artery disease and in control subjects. Methods: This case-control study was performed on 139 subjects who underwent coronary angiography in Shiraz. Plasma vitamin B12 and folate level were measured and compared between patients with CAD and control subjects. Results: 139 individuals with a mean age 56.99±11.93 were enrolled in this study. 31.2% of them had a normal coronary angiography. Mean plasma level of folate in patients with CAD was lower than control subjects (4.46±1.28 ng/ml versus 5.00±1.81 ng/ml, P = 0.04. Also mean plasma level of vitamin B12 in patients CAD and control subjects were 451.43±138.90 and 503.60±199.35 pg/ml respectively. Although mean level of vitamin B12 in patients with CAD was lower than control group, but it was not statistically significant (P = 0.07. Conclusion: Mean plasma level of vitamin B12 and folate were lower in patients with CAD than control group. It seems that supplementation with this vitamins may be useful in patients with CAD.

  3. Efficacy of folate and vitamin B12 in lowering homocysteine concentrations in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Azadibakhsh Nassim

    2009-01-01

    Full Text Available To evaluate the efficacy of supplementation with high dose folic acid with and with-out vitamin B 12 in lowering plasma total homocysteine (tHcy concentrations in hemodialysis (HD patients, we studied 36 HD patients randomized into four groups according to the received thera-peutic regimen: group I (only folic acid (FA, 5 mg/day, group II (FA, 5 mg/day + vitamin B 12 , 1 mg/day group III (only FA, 15 mg/day, group IV (FA, 15 mg/day, vitamin B 12 , 1 mg/day for a period of 8 weeks. Plasma tHcy and serum FA and vitamin B 12 levels were measured at baseline and after the supplementation period. Dietary intakes were assessed during the study period. At baseline, 27.8% of the patients had normal levels of tHcy and 72.2% had hyperhomocysteinemia. After supplementation, plasma tHcy increased by 1.35% in group I and decreased by 6.99%, 14.54% and 30.09% in groups II, III and IV respectively, which was only significant in group IV (P= 0.014. The patients did not show any significant changes in serum folic acid, but a significant change in serum vitamin B 12 in group IV (P= 0.006. Percentage of patients reaching normal levels of plasma tHcy was 5.6 fold higher in group IV than in the reference group (group I. No corre-lations were found between changes of plasma tHcy levels and dietary intakes. We conclude that oral supplementation with 15 mg/day folic acid together with 1 mg/day of vitamin B 12 is effective in reducing tHcy levels in HD patients. These supplements also have a desirable effect on serum folic acid and vitamin B12.

  4. Fasting time and vitamin B12 levels in a community-based population.

    Science.gov (United States)

    Orton, Dennis J; Naugler, Christopher; Sadrzadeh, S M Hossein

    2016-07-01

    Vitamin B12, also known as cobalamin (Cbl), is an essential vitamin that manifests with numerous severe but non-specific symptoms in cases of deficiency. Assessing Cbl status often requires fasting, although this requirement is not standard between institutions. This study evaluated the impact of fasting on Cbl levels in a large community-based cohort in an effort to promote standardization of Cbl testing between sites. Laboratory data for Cbl, fasting time, patient age and sex were obtained from laboratory information service from Calgary Laboratory Services (CLS) for the period of April 2011 to June 2015. CLS is the sole supplier of laboratory services in the Southern Alberta region in Canada (population, approximately 1.4 million). To investigate potential sex-specific effects of fasting on Cbl levels, males and females were analyzed separately using linear regression models. A total of 346,957 individual patient results (196,849 females, 146,085 males) were obtained. The mean plasma Cbl level was 386.5 (±195.6) pmol/L and 412.0 (±220.8) pmol/L for males and females, respectively. Linear regression analysis showed fasting had no significant association with Cbl levels in females; however a statistically significant decrease of 0.9pmol/L/hour fasting (pfasting has the potential to contribute to higher rates of Cbl deficiency in men. Together, these data suggest fasting should be excluded as a requirement for evaluating plasma Cbl. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Dual isotope Schilling test for measuring absorption of food-bound and free vitamin B12 simultaneously

    International Nuclear Information System (INIS)

    Doscherholmen, A.; Silvis, S.; McMahon, J.

    1983-01-01

    A prototype food-bound vitamin B12 (food-B12) absorption test has been developed in which 57 Co-B12 was incorporated in vitro into egg yolk (yolk-B12) and served to volunteers in 50-g cooked portions together with toast and coffee for breakfast. Six hours later, 1 mg nonlabeled B12 was given intramuscularly and 24-hour urine was collected for radioactivity measurement. In separate tests, the absorption of yolk-B12 and crystalline 57 Co-B12 was equally poor in patients with pernicious anemia. However, in patients with simple gastric achlorhydria and those who had undergone gastric surgery, the assimilation of yolk-B12 was impaired greatly, whereas the absorption of crystalline radio-B12 was normal. Egg yolk labeled with 58 Co-B12 was administered together with crystalline 57 Co-B12 in a dual isotope test with results similar to those obtained when the tests were prepared separately. This yolk- 58 Co-B12 test with its ability to detect malabsorption of food-B12 may be considered as an addition to the first part of the Schilling test

  6. Plasma Folate and Vitamin B12 Levels in Patients with Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Lian-Hua Cui

    2016-06-01

    Full Text Available Folate and vitamin B12 involved in the one-carbon metabolism may play a key role in carcinogenesis and progression of hepatocellular carcinoma (HCC through influencing DNA integrity. The purpose of this study is to evaluate the association of plasma folate and vitamin B12 levels with HCC in a case-control study on 312 HCC patients and 325 cancer-free controls. Plasma concentrations of folate and vitamin B12 in all the subjects were measured by electrochemiluminescence immunoassay. Meanwhile, the information of HCC patients’ clinical characteristics including tumor-node-metastasis (TNM stage, tumor size and tumor markers were collected. The patients of HCC had significantly lower folate levels than those of controls; there was no significant difference in the mean of plasma vitamin B12 levels. We also observed an inverse association between the levels of plasma folate and HCC: the adjusted odds ratios (OR (95% confidence intervals (CI of HCC from the highest to lowest quartile of folate were 0.30 (0.15–0.60, 0.33 (0.17–0.65, and 0.19 (0.09–0.38. Compared to the subjects in the lowest quartile of plasma vitamin B12, only the subjects in the highest quartile of vitamin B12 exhibited a significant positive relationship with HCC, the adjusted OR was 2.01 (95% CI, 1.02–3.98. HCC patients with Stage III and IV or bigger tumor size had lower folate and higher vitamin B12 levels. There was no significant difference in the mean plasma folate levels of the HCC cases in tumor markers status (AFP, CEA and CA19-9 levels, whereas patients with higher CEA or CA19-9 levels retained significantly more plasma vitamin B12 than those with normal-CEA or CA19-9 level. In conclusion, plasma folate and vitamin B12 levels could be associated with HCC, and might be used as predictors of clinical characteristics of HCC patients. However, further prospective studies are essential to confirm the observed results.

  7. Serum vitamin B12, folic acid and ferritin levels in patients with migraine

    Directory of Open Access Journals (Sweden)

    Abdullah Acar

    2011-06-01

    Full Text Available OBJECTIVE: It has been reported that disability due to migraine may be reduced with homocysteine-lowering treatment including folic acid and vitamin B12. In addition, recently the periaqueductal gray matter iron deposits have been found to be increased in migraine patients. There are few studies regarding vitamin B12, folic acid, ferritin and transferrin levels in patients with migraine. The aims of this study was to measure vitamin B12, folic acid, ferritin and transferrin levels in patients with migraine and compare them with the control group. METHODS: Fifty-one consecutive newly diagnosed migraine patients who did not receive any vitamin supplement medication were enrolled. The study group consisted of 51 patients, suffering from migraine with aura (n= 23 and migraine without aura (n= 28. The control group consisted of 28 healthy participants without history of headache, anemia and vitamin supplement. Serum vitamin B12, folic acid, ferritin and transferin levels were measured using a chemiluminescence method. RESULTS: Migraine patients had significantly lower concentrations of vitamin B12 and folic acid compared with the healthy controls (for vitamin B12; 215.6±133.7 pg/ml vs. 289.9±12 pg/ml, respectively, p=0.005; for folic acid; 6.74 ± 4.31 pg/ml vs. 8.47 ± 1.85 pg/ml, respectively, p=0.048. The vitamin B12 levels were found to be significantly lower during attacks in migraine patients than in interictal periods (177.3 ± 139.2 pg/ml vs 252.5 ± 119.5 pg/ml, p=0.043. There were no differences in folic acid, ferritin, and transferritin levels between during attacks and in interictal period of patients with migraine (p>0.05. The ferritin levels were found to be significantly lower during attacks in migraine patients than in interictal periods (43.4 ± 41.1 mg/ml, vs 75.4 ± 51.7, mg/ml, p=0.018. CONCLUSION: Migraine patients had lower serum vitamin B12 and folic acid levels than healthy subjects. These findings supported that vitamin B12

  8. Combined indicator of vitamin B 12 status: modification for missing biomarkers and folate status and recommendations for revised cut-points

    Science.gov (United States)

    Background: A novel approach to determine vitamin B 12 status is to combine four blood markers: total B 12 (B 12 ), holotranscobalamin (holoTC), methylmalonic acid (MMA) and total homocysteine (tHcy). This combined indicator of B 12 status is expressed as cB 12 = log 10 [(holoTC · B 12 )/ (MMA · Hcy...

  9. Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development.

    Science.gov (United States)

    Molloy, Anne M; Kirke, Peadar N; Brody, Lawrence C; Scott, John M; Mills, James L

    2008-06-01

    The importance of folate in reproduction can be appreciated by considering that the existence of the vitamin was first suspected from efforts to explain a potentially fatal megaloblastic anemia in young pregnant women in India. Today, low maternal folate status during pregnancy and lactation remains a significant cause of maternal morbidity in some communities. The folate status of the neonate tends to be protected at the expense of maternal stores; nevertheless, there is mounting evidence that inadequate maternal folate status during pregnancy may lead to low infant birthweight, thereby conferring risk of developmental and long-term adverse health outcomes. Moreover, folate-related anemia during childhood and adolescence might predispose children to further infections and disease. The role of folic acid in prevention of neural tube defects (NTD) is now established, and several studies suggest that this protection may extend to some other birth defects. In terms of maternal health, clinical vitamin B12 deficiency may be a cause of infertility or recurrent spontaneous abortion. Starting pregnancy with an inadequate vitamin B12 status may increase risk of birth defects such as NTD, and may contribute to preterm delivery, although this needs further evaluation. Furthermore, inadequate vitamin B12 status in the mother may lead to frank deficiency in the infant if sufficient fetal stores of vitamin B12 are not laid down during pregnancy or are not available in breastmilk. However, the implications of starting pregnancy and lactation with low vitamin B12 status have not been sufficiently researched.

  10. [Vitamin B12 levels in the patient population attending an urban health centre in Madrid].

    Science.gov (United States)

    Camarero-Shelly, M

    2018-04-01

    Vitamin B 12 levels are usually measured in Primary Care when the patients have symptoms or risk factors associated with its deficiency, mostly in the elderly. However, no evidence has been found to support the recommendation of screening in the general population. The aim of this study is to assess the relevance of having extended the screening of vitamin B 12 deficiency to a younger population, after observing an increase in the prescription of this injected vitamin in a population under 65 years, by analysing the vitamin B 12 values obtained. A descriptive, retrospective, observational study was conducted on a sample consisting of 5,531 patients from Barajas Health Primary Centre, Madrid, between 2008 and 2012, and on whom a blood test was performed for any reason, with values of vitamin B 12 . A deficiency was found in 9.1% (SD 2.3) of the patients, of whom 49.4% were less than 65 years. The deficiencies were associated (P<.001, 95% CI) with age, dementia, changes in blood red cell counts, memory, and with the taking of metformin and proton pump inhibitors (P=.007). The prevalence of vitamin B 12 deficiency in our served population is similar in patients older and younger than 65 years. The extended screening was relevant. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Intergenotypic variation of Vitamin B12 and Folate in AD: In north Indian population

    Directory of Open Access Journals (Sweden)

    Neelam Chhillar

    2014-01-01

    Full Text Available Objectives: Changes in lifestyle habits such as diet modification or supplementation have been indicated as probable protective factors for a number of chronic conditions including Alzheimer′s disease (AD. With this background, we aim to hypothesize that whether C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR gene contributes towards the risk of developing AD and its association with vitamin B12 and folate levels. Materials and Methods: A case-control study comprising of total 200 subjects, within the age group of 50-85 years. Their blood samples were analyzed for serum folate, vitamin B12 levels, and MTHFR C677T polymorphism by restriction fragment length polymorphism (RFLP. Results: The mean plasma levels of vitamin B12 and folate were significantly lower in study group when compared to the control group (P < 0.001. Genotypic and allelic frequency of MTHFR gene in both groups was found to be significant (P < 0.05. The intergenotypic variations of vitamin B12 and folate were found to be significant (P < 0.001. Conclusion: We concluded that the subjects with homozygous mutated alleles are more prone to AD and also pointed out the influence of presence/absence of MTHFR T allelic variants on serum folate and vitamin B12 levels.

  12. Analytical electrochemistry of vitamin B12 on a bismuth-film electrode surface

    International Nuclear Information System (INIS)

    Kreft, Gabriel L.; Braga, Otoniel C. de; Spinelli, Almir

    2012-01-01

    Cyclic voltammetry (CV) and square wave adsorptive stripping voltammetry (SWAdSV) were used to investigate the performance of an ex situ plated bismuth-film electrode (BiFE) employed to study the electrochemical behavior and the electroanalytical determination of vitamin B 12 . Two pH-dependent reversible peaks were observed for the B 12r –B 12s (Co(II)–Co(I)) couple after pre-concentration of vitamin B 12 at −1.2 V for 30 s. An adsorption-controlled reaction rate with one electron involved in the electrochemical step was observed for the mechanism implicated. The calibration curve obtained in a Britton–Robinson solution at pH 12.0 was linear in the concentration range of 0.100–1.000 μmol L −1 (r = 0.9980). The detection limit was found to be 33.1 nmol L −1 . The electrode was successfully employed for the determination of vitamin B 12 in two pharmaceutical products. The electrode performance was compared with those of modified and unmodified electrodes as well as with the UV–vis spectrophotometric method.

  13. Determination of vitamin B12 (cobalamine) absorption by means of a simple double-isotope technique

    International Nuclear Information System (INIS)

    Hippe, E.; Brynskov, J.; Gimsing, P.; Hjelt, K.

    1986-01-01

    The background, practical instruction and clinical results of a simplified method of determining the absorption of cobalamine (vitamin B 12 ) are presented. The simultaneous administration of 57 CO-CN-cobalamine, a non-absorbable marker ( 51 CrCl 3 ), and red carmine tablets enable quantitative assessments of the cobalamine absorption by collection of a small red feaces sample. In contrast to the classical Schilling-test, this vitamin B 12 absorption test (B 12 -ABS-test) or faeces-spot-test is, independent of fasting, flushing dose, renal function and diurnal urinary collection. This is documented in a series of clinical studies. The B 12 -ABS-test provides accurate and precise results compared to the reference method (whole-body-counting). The Schilling test, on the contrary, gives approximately 50% false low values in a reference group of elderly hospitalized patients. A modification of the B 12 -ABS-test, has been used to determine the cobalamine absorption in children, and a set of age-related reference intervals have been established, together with quantitative measurements of the cobalamine absorption in children with small bowel diseases. Based on several years of practical experience, we recommend replacement of the Schilling test by this simple double-isotope technique. (author)

  14. Treatment of radiation skin lesions in various stages with different preparations of vitamin B12

    International Nuclear Information System (INIS)

    Ji Hui; Chen Qiang; Yang Xiaohong

    1989-01-01

    Since the aqueous solution of Vit. B 12 was firstly used to treat efficaciously the acute radiation injury of skin and superficial second-degree skin burn, we have successfully treated radiation skin lesions in acute, chronic and recovering stages with the cream or oil preparation of Vit. B 12 . In the period of ten years (1979-1988), altogether 418 cases of radiation or non-radiation skin injury were observed and 48 out of 49 cases with acute radiation skin ulcer treated with aqueous solution of Vit. B 12 were healed with an effective rate of 97.95% and average healing time of 12.6 days. All of 37 cases with chronic radiation skin injury treated with oil preparation of Vit. B 12 were healed or improved with an effective rate of 100% and average healing time of 21.49 days. However, in the control group, of 18 cases treated with conventional drugs only 13 were healed, the effective rate being 72.22% and healing time 63.5 days, and both of these indices were of significant difference, as compared with those treated with Vit. B 12

  15. Use of vitamin B12 radioassay in the analysis of biological materials, mainly of foods

    International Nuclear Information System (INIS)

    Kralova, B.; Rauch, P.; Cerna, J.

    1982-01-01

    Vitamin B 12 was determined in biological materials by three basically different methods: microbiological assay with Lactobacillus leichmannii, microbiological assay with Escherichia coli and radioassay. The method with E. coli has a relatively low sensitivity to vitamin B 12 and in some cases of vitamin B 12 determination in microbial materials it can be used only after a separation of the interfering substances by gel chromatography. The procedure is suitable for orientational determinations of vitamin B 12 because it is very little affected by external factors. The assay with L. leichmannii is universal owing to its high specifity and sensitivity to vitamin B 12 . The main disadvantage of the latter procedure depends on the high requirements for a clean atmosphere which can be maintained in laboratories in industrial areas only with difficulties. These limitations do not apply to the quick and sensitive radioassay. The radioassay can be used after a suitable adjustment of the working procedure for large series of analyses of biological materials without any preliminary separational techniques. (author)

  16. Characterization of extracellular vitamin B12 producing Lactobacillus plantarum strains and assessment of the probiotic potentials.

    Science.gov (United States)

    Li, Ping; Gu, Qing; Yang, Lanlan; Yu, Yue; Wang, Yuejiao

    2017-11-01

    We investigated extracellular vitamin B 12 -producing Lactobacillus strains and their characteristics in tolerance to environmental stresses, gastric acid and bile salts. Two isolates, Lactobacillus plantarum LZ95 and CY2, showed high extracellular B 12 production, 98±15μg/L and 60±9μg/L respectively. Extracellular B 12 from LZ95 were identified as adenosylcobalamin and methylcobalamin using a combination of solid phase extraction and reverse-phase HPLC, while that from CY2 was adenosylcobalamin. Both strains grew under environmental stresses, and LZ95 exhibited better tolerance to low temperature and high ethanol concentration. LZ95 also showed good viability when exposed to gastric acid (pH 2.0 and 3.0) and bile salts (0.3%) as well as good adhesion to Caco-2 cells. The viability of CY2 was significantly reduced under low pH and exposure to bile salt. Together, extracellular B 12 producer LZ95 with good probiotic properties might be a candidate for in situ B 12 fortification in the food industry. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Vitamin B12–dependent taurine synthesis regulates growth and bone mass

    Science.gov (United States)

    Roman-Garcia, Pablo; Quiros-Gonzalez, Isabel; Mottram, Lynda; Lieben, Liesbet; Sharan, Kunal; Wangwiwatsin, Arporn; Tubio, Jose; Lewis, Kirsty; Wilkinson, Debbie; Santhanam, Balaji; Sarper, Nazan; Clare, Simon; Vassiliou, George S.; Velagapudi, Vidya R.; Dougan, Gordon; Yadav, Vijay K.

    2014-01-01

    Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass. PMID:24911144

  18. Stability of added and in situ-produced vitamin B12 in breadmaking.

    Science.gov (United States)

    Edelmann, Minnamari; Chamlagain, Bhawani; Santin, Marco; Kariluoto, Susanna; Piironen, Vieno

    2016-08-01

    Vitamin B12 exists naturally in foods of animal origin and is synthesised only by certain bacteria. New food sources are needed to ensure vitamin B12 intake in risk groups. This study aimed to investigate the stability of added cyanocobalamin (CNCbl, chemically modified form) and hydroxocobalamin (OHCbl, natural form) and in situ-synthesised vitamin B12 in breadmaking. Samples were analysed both with a microbiological (MBA) and a liquid chromatographic (UHPLC) method to test applicability of these two methods. Proofing did not affect CNCbl and OHCbl levels. By contrast, 21% and 31% of OHCbl was lost in oven-baking steps in straight- and sponge-dough processes, respectively, whereas CNCbl remained almost stable. In sourdough baking, 23% of CNCbl and 44% of OHCbl were lost. In situ-produced vitamin B12 was almost as stable as added CNCbl and more stable than OHCbl. The UHPLC method showed its superiority to the MBA in determining the active vitamin B12. Copyright © 2016. Published by Elsevier Ltd.

  19. Associations between Vitamin B-12 Status and Oxidative Stress and Inflammation in Diabetic Vegetarians and Omnivores.

    Science.gov (United States)

    Lee, Yau-Jiunn; Wang, Ming-Yang; Lin, Mon-Chiou; Lin, Ping-Ting

    2016-02-26

    Diabetes is considered an oxidative stress and a chronic inflammatory disease. The purpose of this study was to investigate the correlations between vitamin B-12 status and oxidative stress and inflammation in diabetic vegetarians and omnivores. We enrolled 154 patients with type 2 diabetes (54 vegetarians and 100 omnivores). Levels of fasting glucose, glycohemoglobin (HbA1c), lipid profiles, oxidative stress, antioxidant enzymes activity, and inflammatory makers were measured. Diabetic vegetarians with higher levels of vitamin B-12 (>250 pmol/L) had significantly lower levels of fasting glucose, HbA1c and higher antioxidant enzyme activity (catalase) than those with lower levels of vitamin B-12 (≤ 250 pmol/L). A significant association was found between vitamin B-12 status and fasting glucose (r = -0.17, p = 0.03), HbA1c (r = -0.33, p = 0.02), oxidative stress (oxidized low density lipoprotein-cholesterol, r = -0.19, p = 0.03), and antioxidant enzyme activity (catalase, r = 0.28, p = 0.01) in the diabetic vegetarians; vitamin B-12 status was significantly correlated with inflammatory markers (interleukin-6, r = -0.33, p vegetarian diet.

  20. Purification and characterization of nattokinase from Bacillus subtilis natto B-12.

    Science.gov (United States)

    Wang, Cong; Du, Ming; Zheng, Dongmei; Kong, Fandong; Zu, Guoren; Feng, Yibing

    2009-10-28

    Bacillus subtilis natto B-12 was isolated from natto, a traditional fermented soybean food in Japan. A fibrinolytic enzyme (B-12 nattokinase) was purified from the supernatant of B. subtilis natto B-12 culture broth and showed strong fibrinolytic activity. The enzyme was homogenously purified to 56.1-fold, with a recovery of 43.2% of the initial activity. B-12 nattokinase was demonstrated to be homogeneous by SDS-PAGE and was identified as a monomer of 29000 +/- 300 Da in its native state by SDS-PAGE and size exclusion methods. The optimal pH value and temperature were 8.0 and 40 degrees C, respectively. Purified nattokinase showed high thermostability at temperatures from 30 to 50 degrees C and alkaline stability within the range of pH 6.0-9.0. The enzyme activity was activated by Zn(2+) and obviously inhibited by Fe(3+) and Al(3+). This study provides some important information for the effect factors of fibrinolytic activity, the purification methods, and characterization of nattokinase from B. subtilis natto B-12, which enriches the theoretical information of nattokinase for the research and development of nattokinase as a functional additive of food.

  1. Vitamin B12 Deficiency Presenting as Pancytopenia in Pregnancy: A Case Report

    Directory of Open Access Journals (Sweden)

    Idris N

    2012-12-01

    Full Text Available Vitamin B12 deficiency is a well-known cause of megaloblastic anaemia and pancytopenia. However, the incidence in pregnancy is rarely reported. We present a case of a 32-year old multigravid woman who was diagnosed with megaloblastic anaemia since 22 weeks gestation and progressed to develop severe pancytopenia at 30 weeks gestation. she was also diagnosed with vitamin B12 deficiency related to dietary and sociocultural habits. Folate and iron levels were normal throughout pregnancy. treatment with parenteral cyano-cobalamin resulted in sustained improvement of haematological parameters. the pregnancy was carried to term and the baby was born weighing 2,050gm but otherwise well at birth and had normal developmental milestones thereafter. this case illustrates the clinical presentation of maternal vitamin B12 deficiency and demonstrates the importance of detecting and treating maternal vitamin B12 deficiency during pregnancy in at-risk patients. Failure to diagnose and institute treatment carries significant risks to both mother and child. oral vitamin B12 supplementation should be considered for patients who are strict vegetarians or consume very little animal products.

  2. Clinical Significances of Serum Vitamin B12, Folate and Ferritin Levels in Patients with Malignant Tumors

    International Nuclear Information System (INIS)

    Monn, Youn Sung; Soung, In Whan; Kim, Sam Yong; Ro, Heung Kyu; Lee, Bok Hee

    1987-01-01

    In order to evaluate the clinical significances of the serum vitamin B 12 , folate and ferritin levels in patients with malignant tumors, the levels were measured in 10 normal control subjects, 70 patients with malignant tumors, 7 patients with liver cirrhosis and 25 patients with other benign diseases. The results are as follows: 1) In normal control subjects, mean serum values for vitamin B 12 , folate and ferritin level were 588.80±131.58 pg/ml, 5.59±1.52 ng/ml and 89.22±42.78 ng/ml retrospectively. 2) There was no significant difference in serum levels between patients with benign diseases and normal control subjects. 3) The serum vitamin B 12 and ferritin levels in patients with liver cirrhosis were significantly higher than in normal control, and the serum folate levels in these patients were lower than in normal control subjects. 4) The serum vitamin B 12 and ferritin levels in patients with malignant tumors were significantly higher than in normal control subjects, and the serum folate levels in these patients were significantly lower than in normal control subjects. The above results suggest that the serum vitamin B 12 and ferritin may be useful as tumor markers in patients with malignant tumors.

  3. Vitamin B-12 concentrations in breast milk are low and are not associated with reported household hunger, recent animal source food or vitamin B-12 intake among women in rural Kenya

    Science.gov (United States)

    Background: Breastmilk vitamin B-12 concentration may be inadequate in mothers living in regions where animal source food consumption is low or infrequent. Vitamin B-12 deficiency causes megaloglastic anemia and impairs growth and development in children. Objective: To measure vitamin B-12 in breast...

  4. Antibody Treatment of Ebola and Sudan Virus Infection via a Uniquely Exposed Epitope within the Glycoprotein Receptor Binding Site

    Science.gov (United States)

    2016-06-14

    defective particles. For example, studies performed with anti-EBOV equine immunoglobulin clearly showed rapid reduction in EBOV specific equine IgG...titer during the peak of viremia in NHPs, while total equine IgG titer remained constant (Jahrling et al., 1996), suggesting high antibody consumption... therapy of Ebola hemorrhagic fever. J Infect Dis 179 Suppl 1, S248-258. Coughlin, M.M., and Prabhakar, B.S. (2012). Neutralizing human monoclonal

  5. Sensory Neuronopathy Revealing Severe Vitamin B12 Deficiency in a Patient with Anorexia Nervosa: An Often-Forgotten Reversible Cause

    Directory of Open Access Journals (Sweden)

    Jérôme Franques

    2017-03-01

    Full Text Available Vitamin B12 (B12 deficiency is known to be associated with various neurological manifestations. Although central manifestations such as dementia or subacute combined degeneration are the most classic, neurological manifestations also include sensory neuropathies. However, B12 deficiency is still rarely integrated as a potential cause of sensory neuronopathy. Moreover, as many medical conditions can falsely normalize serum B12 levels even in the context of a real B12 deficiency, some cases may easily remain underdiagnosed. We report the illustrating case of an anorexic patient with sensory neuronopathy and consistently normal serum B12 levels. After all classical causes of sensory neuronopathy were ruled out, her clinical and electrophysiological conditions first worsened after folate administration, but finally improved dramatically after B12 administration. B12 deficiency should be systematically part of the etiologic workup of sensory neuronopathy, especially in a high risk context such as anorexia nervosa.

  6. The relationship between cerebrovascular disease and homocysteine, folate and vitamin B12 in serum

    International Nuclear Information System (INIS)

    Wang Wei; Yang Chen; Shi Yizhen; Liu Zengli

    2005-01-01

    To investigate the relationship between cerebrovascular disease and the serum levels of homocysteine(Hcy), folate and vitamin B 12 , the serum levels of Hcy, folate and vitamin B 12 in 148 patients with cerebrovascular disease were measured by fluorescence polarization immuno- assay and chemiluminescence and were compared with those in healthy controls. The result showed that the serum Hcy levels in patients with cerebral infarction, cerebral hemorrhage and vertebrobasilar ischemiay were significantly higher than those in healthy controls (P 12 levels were signifieantly lower (P 0.05). No significantly higher ratio of increased Hcy levels was observed in patient with complications (P> 0.05). Our conclusion is that hyperhomocysteinemia may be a new and an independent risk factor for cerebrovascular disease. The serum Hcy level is correlated with decreased levels of folate and vitamin B 12 but not obviously correlated with hypertension, diabetes and coronary heart disease. (authors)

  7. Clinical observation of vitamin B12 eye drops for vision fatigue caused by visual display terminals

    Directory of Open Access Journals (Sweden)

    Qiang Guo

    2016-07-01

    Full Text Available AIM: To investigate the clinical effect of vitamin B12 eye drops for vision fatigue caused by visual display terminals(VDT. METHODS: Totally 50 patients(100 eyeswith vision fatigue caused by VDT were averagely divided into two groups. The control group were treated with normal saline,the treatment group were treated with vitamin B12 eye drops,3 times per day, one drop each time, continuous for 60d. Accommodative parameters and Schirmer Ⅰtest were measured and analyzed before and after treatment. RESULTS:After treatment, the results of Schirmer Ⅰtest, accommodative amplitude and accommodative facility of the treatment group were higher than those of the control group(all PPCONCLUSION: Vitamin B12 eye drops can lessen symptoms of dry eye, improve accommodative function and treat vision fatigue caused by VDT.

  8. Iron, folacin, vitamin B12 and zinc status and immune response in the elderly

    International Nuclear Information System (INIS)

    Henry-Christian, J.R.; Johnson, A.A.; Walters, C.S.; Greene, E.J.; Lindsey, A.A.

    1986-01-01

    The relationships of iron, folacin, vitamin B 12 and zinc status to cell-mediated immune response were investigated among 125 healthy, elderly persons (60-87 years of age). Plasma ferritin, plasma and red cell folate, and plasma vitamin B 12 levels were assayed immuno-radiometrically. Plasma and hair zinc levels were determined by atomic absorption spectroscopy. Immune response was determined by transformation of peripheral blood lymphocytes after stimulation with phytohemagglutinin (PHA) and concanavalin A (con A), and in mixed lymphocyte reaction. Deficiencies of iron, folacin vitamin B 12 and zinc were each associated (independently) with significantly lower lymphocyte responses to PHA and con A, and mixed lymphocyte reaction (P 12 or zinc. Further, they suggest that deficiencies of these nutrients may play a role in the depression of cell-mediated immunity with age, which in turn may lead to increased susceptibility to infectious diseases and cancer in the elderly

  9. Vitamin B12 and folate levels in normal population of northern Pakistan

    International Nuclear Information System (INIS)

    Madood-ul-mannan; Anwar, M.; Saleem, M.; Waqar, A.; Ahmad, M.

    1990-01-01

    Diagnosis of vitamin B12 or folate deficiency can not be made unless reference ranges of these vitamins in a given population are known. These serum levels depend upon the dietary intake of these vitamins which in turn depends upon the availability of foods containing these vitamins and the methods of cooking/processing. The latter vary in different populations. Therefore serum level of these vitamins would vary in different populations. Serum levels of vitamin B12 and folate were estimated by radioimmunoassay technique in 30 normal subjects of different age groups. The levels of vitamin B12 were found to be 215.2 pg/ml and that of folate 3.9 ng/ml. These values are much lower than those described for European population. It is therefore concluded that the cut off point of the levels of these vitamins should be different than the European figures. (author)

  10. Vitamin B12-catalyzed synthesis of some peracetylated alkyl b-D-xylopyranosides

    Directory of Open Access Journals (Sweden)

    LJILJANA STEVANOVIC

    2003-10-01

    Full Text Available The vitamin B12-catalyzed glycosylation reaction of brominated b-D-xylose peracetate with alkanols ROH (C1-C8 has been studied. The catalytically active species in this reaction was cob(Ialamin, obtained by chemical reduction of Vitamin B12 with NaBH4 (Co(III to Co(I. The reaction was carried out with 2 mol% of vitamin B12, with respect to xylosyl bromide 1, under argon at room temperature. Under these conditions, peracetylated C1-C8-alkyl b-D-xylopyranosides (3a–3f were obtained in moderate yield (55–70 %. In all cases 3,4-di-O-acetyl-D-xylal (4 was obtained, as the product of reductive elimination of peracetylated xylosyl bromide (15–25 %.

  11. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site.

    Directory of Open Access Journals (Sweden)

    Ema T Crooks

    2015-05-01

    Full Text Available Eliciting broad tier 2 neutralizing antibodies (nAbs is a major goal of HIV-1 vaccine research. Here we investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit nAbs. Unusually potent nAb titers developed in 2 of 8 rabbits immunized with virus-like particles (VLPs expressing trimers (trimer VLP sera and in 1 of 20 rabbits immunized with DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. Specifically, trimer VLP sera took advantage of the unusual absence of a glycan at residue 197 (present in 98.7% of Envs. Intriguingly, removing the N197 glycan (with no loss of tier 2 phenotype rendered 50% or 16.7% (n = 18 of clade B tier 2 isolates sensitive to the two trimer VLP sera, showing broad neutralization via the surface masked by the N197 glycan. Neutralizing sera targeted epitopes that overlap with the CD4 binding site, consistent with the role of the N197 glycan in a putative "glycan fence" that limits access to this region. A bioinformatics analysis suggested shared features of one of the trimer VLP sera and monoclonal antibody PG9, consistent with its trimer-dependency. The neutralizing DNA trimer serum took advantage of the absence of a glycan at residue 230, also proximal to the CD4 binding site and suggesting an epitope similar to that of monoclonal antibody 8ANC195, albeit lacking tier 2 breadth. Taken together, our data show for the first time that strain-specific holes in the glycan fence can allow the development of tier 2 neutralizing antibodies to native spikes. Moreover, cross-neutralization can occur in the absence of protecting glycan. Overall, our observations provide new insights that may inform the future development of a neutralizing antibody vaccine.

  12. NutriPhone: vitamin B12 testing on your smartphone (Conference Presentation)

    Science.gov (United States)

    Lee, Seoho; O'Dell, Dakota; Hohenstein, Jessica; Colt, Susannah; Mehta, Saurabh; Erickson, David

    2016-03-01

    Vitamin B12 deficiency is the leading cause of cognitive decline in the elderly and is associated with increased risks of several acute and chronic conditions including anemia. The deficiency is prevalent among the world population, most of whom are unaware of their condition due to the lack of a simple diagnostics system. Recent advancements in the smartphone-enabled mobile health can help address this problem by making the deficiency tests more accessible. Previously, our group has demonstrated the NutriPhone, a smartphone platform for the accurate quantification of vitamin D levels. The NutriPhone technology comprises of a disposable test strip that performs a colorimetric reaction upon collecting a sample, a reusable accessory that interfaces with the smartphone camera, and a smartphone app that stores the algorithm for analyzing the test-strip reaction. In this work, we show that the NutriPhone can be expanded to measure vitamin B12 concentrations by developing a lateral flow assay for B12 that is compatible with our NutriPhone system. Our novel vitamin B12 assay incorporates blood sample processing and key reagent storage on-chip, which advances it into a sample-in-answer-out format that is suitable for point-of-care diagnostic applications. In order to enable the detection of pM levels of vitamin B12 levels, silver amplification of the initial signal is used within the total assay time of less than 15 minutes. We demonstrate the effectiveness of our NutriPhone system by deploying it in a resource-limited clinical setting in India where it is used to test tens of participants for vitamin B12 deficiency.

  13. Vitamin B12 deficiency evaluation and treatment in severe dry eye disease with neuropathic ocular pain.

    Science.gov (United States)

    Ozen, Serkan; Ozer, Murat Atabey; Akdemir, Mehmet Orçun

    2017-06-01

    This study aims to understand the effect of vitamin B12 deficiency on neuropathic ocular pain (NOP) and symptoms in patients with dry eye disease (DED). Patients with severe DED (without receiving topical artificial tears treatment) and ocular pain were enrolled (n = 90). Patients with severe DED and vitamin B12 deficiency (group 1, n = 45) received parenteral vitamin B12 supplement + topical treatment (artificial tears treatment + cyclosporine), and patients with severe DED and normal serum vitamin B12 level (group 2, n = 45) received only topical treatment (artificial tears treatment + cyclosporine). Patients were evaluated by the ocular surface disease index (OSDI) questionnaire, 3rd question (have you experienced painful or sore eyes during last week?) score of OSDI as a pain determiner and pain frequency measure), tear break up time (TBUT), and Schirmer's type 1 test. We compared the groups' OSDI, TBUT, and Schirmer's test recordings at the first visit and after 12 weeks retrospectively. The OSDI score, 3rd OSDI question score, TBUT, and Schirmer's test results improved after 12 weeks (p treatment. The mean score changes between the groups were not statistically significant; however, the decrease in the OSDI questionnaire score (-30.80 ±5.24) and 3rd OSDI question score (-2.82 ±0.53) were remarkable in group 1 (Table 2). The mean TBUT increase was +7.98 ±2.90 s and Schirmer's test result increase was +12.16 ±2.01 mm in group 1. The mean TBUT increase was +6.18 ±1.49 s and Schirmer's test result increase was +6.71 ±1.47 mm in group 2. These findings indicate that vitamin B12 deficiency is related with NOP. It may be important to consider measuring the serum vitamin B12 level in patients with severe DED presenting with resistant ocular pain despite taking topical treatment.

  14. Serum homocysteine, folate, vitamin B12 and total antioxidant status in vegetarian children.

    Science.gov (United States)

    Ambroszkiewicz, J; Klemarczyk, W; Chełchowska, M; Gajewska, J; Laskowska-Klita, T

    2006-01-01

    The results of several studies point to the positive role of vegetarian diets in reducing the risk of diabetes, some cancers and cardiovascular diseases. However, exclusion of animal products in vegetarian diets may affect the cobalamin status and cause an elevation of the plasma homocysteine level. The aim of this study was to assess the effect of vegetarian diets on serum concentrations of homocysteine, folate, vitamin B12 and total antioxidant status (TAS) in children. The study included 32 vegetarians (including 5 vegans), age 2-10 years. Dietary constituents were analyzed using a local nutritional programme. Serum homocysteine, folate and vitamin B12 were determined with fluorescence and chemiluminescence immunoassays. The concentration of TAS was measured by a colorimetric method. Average daily energy intake and the percentage of energy from protein, fat and carbohydrates in the diets of the studied children were just above or similar to the recommended amounts. It could be shown that vegetarian diets contain high concentrations of folate. In vegan diets it even exceeds the recommended dietary allowance. Mean daily intake of vitamin B12 in the studied diets was adequate but in vegans was below the recommended range. The serum concentrations of homocysteine, folate, vitamin B12 and TAS in vegetarian children remained within the physiological range. The presented data indicate that vegetarian children, contrary to adults, have enough vitamin B12 in their diet (excluding vegans) and normal serum concentrations of homocysteine, folate and vitamin B12. Therefore, in order to prevent deficiencies in the future, close monitoring of vegetarian children (especially on a vegan diet) is important to make sure that they receive adequate quantities of nutrients needed for healthy growth.

  15. A Computational Tale of Two Enzymes: Glycerol Dehydration With or Without B12.

    Science.gov (United States)

    Kovačević, Borislav; Barić, Danijela; Babic, Darko; Bilić, Luka; Hanževački, Marko; Sandala, Gregory M; Radom, Leo; Smith, David M

    2018-06-12

    We present a series of QM/MM calculations aimed at understanding the mechanism of the biological dehydration of glycerol. Strikingly and unusually, this process is catalyzed by two different radical enzymes, one of which is a coenzyme-B 12 - dependent enzyme and the other which is a coenzyme-B 12 - independent enzyme. We show that glycerol dehydration in the presence of the coenzyme-B 12 -dependent enzyme proceeds via a 1,2-OH shift, which benefits from a significant catalytic reduction in the barrier. In contrast, the same reaction in the presence of the coenzyme-B 12 -independent enzyme is unlikely to involve the 1,2-OH shift; instead, a strong preference for direct loss of water from a radical intermediate is indicated. We show that this preference and, ultimately the evolution of such enzymes, is strongly linked with the reactivities of the species responsible for abstracting a hydrogen atom from the substrate. It appears that the hydrogen re-abstraction step involving the product-related radical is fundamental to the mechanistic preference. The unconventional 1,2-OH shift seems to be required to generate a product-related radical of sufficient reactivity to cleave the relatively inactive C-H bond arising from the B 12 cofactor. In the absence of B 12 , it is the relatively weak S-H bond of a cysteine residue that must be homolyzed. Such a transformation is much less demanding and its inclusion apparently enables a simpler overall dehydration mechanism.

  16. Site-specific antibody-liposome conjugation through copper-free click chemistry: a molecular biology approach for targeted photodynamic therapy (Conference Presentation)

    Science.gov (United States)

    Obaid, Girgis; Wang, Yucheng; Kuriakose, Jerrin; Broekgaarden, Mans; Alkhateeb, Ahmed; Bulin, Anne-Laure; Hui, James; Tsourkas, Andrew; Hasan, Tayyaba

    2016-03-01

    Nanocarriers, such as liposomes, have the ability to potentiate photodynamic therapy (PDT) treatment regimens by the encapsulation of high payloads of photosensitizers and enhance their passive delivery to tumors through the enhanced permeability and retention effect. By conjugating targeting moieties to the surface of the liposomal nanoconstructs, cellular selectivity is imparted on them and PDT-based therapies can be performed with significantly higher dose tolerances, as off-target toxicity is simultaneously reduced.1 However, the maximal benefits of conventional targeted nanocarriers, including liposomes, are hindered by practical limitations including chemical instability, non-selective conjugation chemistry, poor control over ligand orientation, and loss of ligand functionality following conjugation, amongst others.2 We have developed a robust, physically and chemically stable liposomal nanoplatform containing benzoporphyrin derivative photosensitizer molecules within the phospholipid bilayer and an optimized surface density of strained cyclooctyne moieties for `click' conjugation to azido-functionalized antibodies.3 The clinical chimeric anti-EGFR antibody Cetuximab is site-specifically photocrosslinked to a recombinant bioengineered that recognizes the antibody's Fc region, containing a terminal azide.4 The copper-free click conjugation of the bioengineered Cetuximab derivative to the optimized photosensitizing liposome provides exceptional control over the antibody's optimal orientation for cellular antigen binding. Importantly, the reaction occurs rapidly under physiological conditions, bioorthogonally (selectively in the presence of other biomolecules) and without the need for toxic copper catalysis.3 Such state-of-the-art conjugation strategies push the boundaries of targeted photodynamic therapy beyond the limitations of traditional chemical coupling techniques to produce more robust and effective targeted therapeutics with applications beyond

  17. Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older hispanics

    Science.gov (United States)

    Background: A common polymorphism, C776G, in the plasma B12 transport protein transcobalamin (TC), encodes for either proline or arginine at codon 259. This polymorphism may affect the affinity of TC for B12 and subsequent delivery of B12 to tissues. Methods: TC genotype and its associations with i...

  18. Fisiopatologia da deficiência de vitamina B12 e seu diagnóstico laboratorial

    OpenAIRE

    Paniz,Clóvis; Grotto,Denise; Schmitt,Gabriela Cristina; Valentini,Juliana; Schott,Karen Lílian; Pomblum,Valdeci Juarez; Garcia,Solange Cristina

    2005-01-01

    INTRODUÇÃO: A vitamina B12 é hidrossolúvel, não-sintetizada pelo organismo humano, presente em alimentos de origem animal. Sua deficiência é muito freqüente entre idosos, vegetarianos e indivíduos que adotam baixa dieta protéica ou apresentam problemas de absorção gastrintestinal. FISIOPATOLOGIA: A deficiência de vitamina B12 leva a transtornos hematológicos, neurológicos e cardiovasculares, principalmente, por interferir no metabolismo da homocisteína (Hcy) e nas reações de metilação do orga...

  19. Biosynthesis of vitamin B12: concerning the origin of the methine protons of the corrin nucleus

    International Nuclear Information System (INIS)

    Scott, A.I.; Kajiwara, M.; Santander, P.J.

    1987-01-01

    13C NMR spectroscopy has been used to locate six deuterium atoms incorporated biosynthetically on the periphery of the corrin nucleus of vitamin B12 (cyanocobalamin) derived from cells of Propionibacterium shermanii grown in a medium containing 50% 2 H 2 O and 13 C-enriched delta-aminolevulinic acid. The implications of these results for the mechanism of vitamin B12 biosynthesis are discussed, and it is concluded that the same oxidation level of the intermediates is maintained throughout the biosynthetic pathway, from delta-aminolevulinic acid to corrin

  20. CA 15-3 predicting breast cancer relapse: beware of vitamin B12 deficiency.

    Science.gov (United States)

    Rassy, Elie El; Ghor, Maya Al; Kattan, Joseph

    2018-05-10

    A sustained increase of cancer antigen 15-3 serum levels was found in a 54-year-old woman treated 2 years ago for early stage breast cancer, without any evidence of cancer recurrence. The patient thereafter developed severe megaloblastic anemia secondary to vitamin B12 deficiency. Supplementation with B12 to reverse the anemia led to the normalization of the cancer antigen 15-3 serum levels. As such, with the limited understanding of molecular biology, the integrative approach of clinical history, physical examination, and diagnostic imaging remain pivotal in the management of cancer patients.

  1. Reversible Vitamin B12 Deficiency Presenting with Acute Dementia, Paraparesis, and Normal Hemoglobin

    Directory of Open Access Journals (Sweden)

    Hani Almoallim

    2016-01-01

    Full Text Available Vitamin B12 is essential for neurological function and its deficiency is associated with many neuropsychiatric disorders. We report the case of a previously healthy 53-year-old male patient presenting with delirium and multiple neurological findings. Complete blood analysis indicated megaloblastic anemia. All infectious causes were excluded owing to negative cultures (blood and urine. Tests for human immunodeficiency virus, syphilis, and toxoplasma were also negative. Metabolic workup showed severe vitamin B12 deficiency, decreased reticulocyte count, and increased direct bilirubin and lactate dehydrogenase. Intramuscular injection of cobalamin was started, and the patient showed significant improvement.

  2. [Evaluation of the needs and possibilities of increasing the vitamin B12 content in diet].

    Science.gov (United States)

    Sicińska, Ewa; Cholewa, Małgorzata

    2012-01-01

    Vitamin B12 belongs to the biologically active compounds related to cyanocobalamin group. The bioavailability of B12 from different food products varies considerably, for example from the chicken meat it ranges from 61 to 66%, from fish meat is 42%, and from eggs below 9% only. The deficiency of vitamin B12 could easily be overcame by the appropriate diet or food supplements. The aim of this study was to characterize the fortified with vitamin B12 food products available on the market and to assess the possibilities of increasing the intake of this vitamin by including such products into the daily diet. The study was carried out in winter 2011, at eleven Warsaw supermarkets. Information about food products was based on label declarations. There were 220 products fortified with vitamin B12 from various food categories, like breakfast cereals, fruit juice, non-alcoholic beverages, cereals bars, candies, instant cocoa and tea, margarine, as well as soya products. Breakfast cereals (40%) and juice, non-alcoholic beverages (30%) were the largest groups. RESULTS. The highest amount of vitamin B12 was found in some candies (max. 4,5 microg/100 g) and instant tea (max. 3,75 microg/100g). The lowest amount was found in some fruit beverages (min. 0,12 microg/100 g). There is possibility of increasing the vitamin B12 intake by consuming various fortified products: for instance a glass of soya drink (20,8% RDA), a cup of soya pudding (15%), a glass of instant tea (14%), apple juice (12,5%), a cereal bar (10%), a bowl of corn flakes (9,8%) or a slice of bread with margarine (7,5%). The intake of one average portion of chosen food products fortified with vitamin B12 provides about 0,18-0,5 microg (7,5-20,8% Polish RDA for adults). The wide public education is essential for increasing the role of these products in nutrition, it is especially recommendable to vegetarian and elderly people.

  3. Lessons to be learned: a case study approach. Vitamin B12 deficiency of nutritional origin.

    Science.gov (United States)

    Donaldson, D

    1997-10-01

    The case is presented of a 14 year old boy who developed severe anaemia at the onset of puberty caused by nutritional deficiency of vitamin B12 of about 10 years duration. The dietary intake comprised mainly chips, ice-cream, fruit and Coca-Cola--with small amounts of vitamin B12 from occasional slices of chicken meat. His denial of abnormal nutritional intake, supported by his mother, delayed confirmation of the correct diagnosis. However, the true situation was eventually confessed--and following implementation of a normal diet he rapidly improved clinically, the haemoglobin value rose to normal and he subsequently remained well.

  4. Vitamin B12 supplementation and cognitive scores in geriatric patients with Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Komal Chauhan

    2016-09-01

    Full Text Available Background: The Neurodegenerative diseases are increasingly affecting the elderly with a severe impact on their brain health. There is a wide gap in supplementation based studies for increasing the cognition levels of the geriatric population, especially in developing countries like India which are at extreme risk of developing neurological disorders. And recently Vitamin B12 has drawn considerable attention due to its ability to improve the cognitive status. Current literature has linked the possibility of alleviating neurological disorders in the elderly with effective vitamin B12 management. Abundant animal and human models have proved that supplementation of vitamin B12 is beneficial for the restoration of cognitive functions. Objective: To supplement vitamin B12 deficient mild cognitively impaired geriatric patients with injectable doses of vitamin B12 followed by impact evaluation. Methods: Screening of the mild cognitively impaired patients was carried out using the Mini- Mental State Examination and Yamaguchi Fox Pigeon Imitation test. Baseline information was elicited from the patients residing in urban Vadodara (a district in the state of Gujarat, India. This included socio-demographic, medical and drug history, anthropometric and physical activity pattern, in addition to biochemical parameters comprising of serum vitamin B12 and glycated haemoglobin profile. A sub-sample of 60 patients with mild cognitive impairment (MCI demonstrating severe vitamin B12 deficiency were conveniently enrolled for injectable doses of Vitamin B 12 in the dosage of 1,000 µg every day for one week, followed by 1,000 µg every week for 4 weeks & finishing with 1,000 µg for the remaining 4 months. An intervention six- month after the experiment with all the parameters were elicited. Results: Vitamin B12 supplementation resulted in a significant (p<0.001 improvement in the MMSE scores of the patients with a rise of 9.63% in the total patients. Gender

  5. Homocisteína, folato e vitamina B12 em pacientes colombianos portadores de coronariopatia Homocysteine, folate and vitamin B12 in colombian patients with coronary disease

    Directory of Open Access Journals (Sweden)

    Gilberto Garcia

    2007-08-01

    Full Text Available OBJETIVO: Determinar a existência de associação entre os níveis plasmáticos de homocisteína, folato ou vitamina B12 e síndrome coronariana aguda em pacientes colombianos. MÉTODOS: Estudo caso-controle: foram 50 pacientes portadores de síndrome coronariana aguda e 50 pacientes ambulatoriais sem síndrome coronariana. Foram medidos os níveis de homocisteína, folato e vitamina B12 por meio de imunoensaio por quimioluminescência. Foram também medidos os níveis de colesterol e frações, triglicérides, uréia, creatinina, hemoglobina e hematócrito. RESULTADOS: As concentrações plasmáticas médias de homocisteína foram significativamente diferentes entre os casos (12,4 µmol/l ± 6,0 e os controles (9,7 µmol/l ± 2,4, p=0,01. Os níveis de ácido fólico dos casos foram menores que os dos controles (respectivamente 10,5 ng/ml ± 3,5 x 12,6 ng/ml ± 3,6; p=0,01. Foi observada relação inversa entre os níveis de folato e os de homocisteína. Não houve relação entre os níveis de vitamina B12 e os de homocisteína. Houve diferença significativa nos níveis de triglicérides entre os grupos caso e controle (respectivamente 136,91 ± 67,27 x 174,3 ± 77,6; p=0,01. A razão das chances para hiper-homocisteinemia na síndrome coronariana aguda foi de 4,45 (intervalo de confiança de 95%: 1,5 - 13,3. CONCLUSÃO: O presente estudo demonstrou associação significativa entre os níveis de homocisteína e síndrome coronariana aguda em pacientes colombianos semelhante à encontrada em populações européias e norte-americanas. Houve correlação negativa entre os níveis plasmáticos de homocisteína e os de folato. Não houve associação entre os níveis plasmáticos de homocisteína e os de vitamina B12.OBJECTIVE: To determine the occurrence of association between homocysteine, folate, or vitamin B12 plasma levels and acute coronary syndrome in Colombian patients. METHODS: Case control study: cases were 50 patients with acute

  6. Method of stably radiolabeling antibodies with technetium and rhenium

    International Nuclear Information System (INIS)

    Paik, C.H.; Reba, R.C.; Eckelman, W.C.

    1987-01-01

    A method is described for labeling antibodies or antibody fragments with radionuclides of technetium or rhenium to obtain stable labeling, comprising: reacting a reduced radioisotope of technetium or rhenium with an antibody or antibody fragment, or a diethylenetriaminepentaacetic acid conjugated antibody or antibody fragment, in the presence of free or carrier-bound diethylenetriaminepentaacetic acid (DTPA). The amount of DTPA is sufficient to substantially completely inhibit binding of the reduced technetium or rhenium to nonstable binding sites of the antibody or antibody fragment, or the DTPA-conjugated antibody or antibody fragment. The resultant stably labeled antibody or antibody fragment, or DTPA[conjugated antibody or antibody fragment is recovered

  7. Prevalence of anemia and deficiencies of iron, folic acid and vitamin B12 in an indigenous community from the Venezuelan Amazon with a high incidence of malaria.

    Science.gov (United States)

    García-Casal, Maria Nieves; Leets, Irene; Bracho, Carmen; Hidalgo, Mariana; Bastidas, Gilberto; Gomez, Ana; Peña, Ana; Pérez, Hilda

    2008-03-01

    The objective of this work was to determine the prevalence of anemia and deficiencies of iron, folic acid and vitamin B12 in Betania del Topocho, a Piaroa community from Estado Amazonas, Venezuela, a zone with a high incidence of malaria. The group studied included 184 subjects of all ages that assisted to the local health center for malaria diagnosis. Analysis performed included hematology by coulter counter, ferritin quantification by ELISA with monoclonal antibodies and folic acid and vitamin B12 determinations by an immunoradiometric assay. It was found that the prevalence of anemia was 89.6% and deficiencies of iron, folic acid and vitamin B12 affected 37.1,70.3 and 12.4% of the population studied, respectively. Plasmodium infection was detected by molecular diagnosis in 53.2% of the cases, and 86% of them were anemic. The highest incidence of anemia was found in children, with a prevalence of 100% in infants of both sexes. The high prevalence of anemia, iron and folic acid deficiencies found, indicates an important health and nutrition problem that should be immediately and properly addressed. The number of cases of anemia due to iron deficiency could be underestimated, since ferritin concentration increased as a acute phase protein, although prevalence data was also analyzed with a cutoff point of 30 microg/L for ferritin concentration.

  8. Hepatitis A virus antibody

    International Nuclear Information System (INIS)

    Novak, J.; Kselikova, M.; Urbankova, J.

    1980-01-01

    A description is presented of a radioimmunoassay designed to prove the presence of the antibody against the hepatitis A virus (HA Ab, anti-Ha) using an Abbott HAVAB set. This proof as well as the proof of the antibody against the nucleus of the hepatitis B virus is based on competition between a normal antibody against hepatitis A virus and a 125 I-labelled antibody for the binding sites of a specific antigen spread all over the surface of a tiny ball; this is then indirect proof of the antibody under investigation. The method is described of reading the results from the number of impulses per 60 seconds: the higher the titre of the antibody against the hepatitis A virus in the serum examined, the lower the activity of the specimen concerned. The rate is reported of incidence of the antibody against the hepatitis A virus in a total of 68 convalescents after hepatitis A; the antibody was found in 94.1%. The immunoglobulin made from the convalescents' plasma showed the presence of antibodies in dilutions as high as 1:250 000 while the comparable ratio for normal immunoglobulin Norga was only 1:2500. Differences are discussed in the time incidence of the antibodies against the hepatitis A virus, the antibodies against the surface antigen of hepatitis B, and the antibody against the nucleus of the hepatitis V virus. (author)

  9. Phylogenetic analysis of vitamin B12-related metabolism in Mycobacterium tuberculosis

    OpenAIRE

    Young, Douglas B.; Comas, I?aki; de Carvalho, Luiz P. S.

    2015-01-01

    Comparison of genome sequences from clinical isolates of Mycobacterium tuberculosis with phylogenetically-related pathogens Mycobacterium marinum, Mycobacterium kansasii, and Mycobacterium leprae reveals diversity amongst genes associated with vitamin B12-related metabolism. Diversity is generated by gene deletion events, differential acquisition of genes by horizontal transfer, and single nucleotide polymorphisms (SNPs) with predicted impact on protein function and transcriptional regulation...

  10. Vitamin B12 deficiency might be related to sarcopenia in older adults.

    Science.gov (United States)

    Bulut, Esra Ates; Soysal, Pinar; Aydin, Ali Ekrem; Dokuzlar, Ozge; Kocyigit, Suleyman Emre; Isik, Ahmet Turan

    2017-09-01

    Sarcopenia and dynapenia are related to repeated falls, mobility restriction, depression, frailty, increased mortality and morbidity. The aim of this study is to evaluate the relationship between vitamin B12 deficiency and sarcopenia in older adults. 403 patients, who attended to outpatient clinic and underwent comprehensive geriatric assessment, were included study. All cases' skeletal muscle mass (SMM), walking speed and hand grip strength were recorded by bioimpedance, 4meter walking test and hand dynamometer respectively. The diagnosis of sarcopenia was defined according to the criteria of the European Working Group on Sarcopenia in Older People. Sarcopenia was accepted low SMM with low handgrip strength or low physical performance. Dynapenia was defined as handgrip strength sarcopenia and dynapenia was 24.8% and 32.0%, respectively. In the patients with sarcopenia, mean age, osteoporosis and frailty were higher, and MMSE, and instrumental ADL scores were lower than the patients without sarcopenia (psarcopenia and dynapenia were 31.6% and 35.4%, respectively, in patients with vitamin B12 levels Sarcopenia, which results in lots of negative clinical outcomes in older adults, might be related to vitamin B12 deficiency. Therefore, these patients should be periodically examined for vitamin B12 deficiency due to the potential negative clinical outcomes such as sarcopenia in older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Lifestyle and genetic determinants of folate and vitamin B12 levels in a general adult population

    DEFF Research Database (Denmark)

    Thuesen, Betina H; Husemoen, Lise Lotte N; Ovesen, Lars

    2009-01-01

    and the prevalence was lower with increasing age. Low serum folate was associated with smoking, low alcohol intake, high coffee intake, unhealthy diet, and the TT genotype of the methylenetetrahydrofolate reductase (MTHFR)-C677T polymorphism. The overall prevalence of low serum vitamin B12 (

  12. Serum folate, vitamin B-12 and cognitive function in middle and older age: The HAPIEE study.

    Science.gov (United States)

    Horvat, Pia; Gardiner, Julian; Kubinova, Ruzena; Pajak, Andrzej; Tamosiunas, Abdonas; Schöttker, Ben; Pikhart, Hynek; Peasey, Anne; Jansen, Eugene; Bobak, Martin

    2016-04-01

    Nutrient status of B vitamins, particularly folate and vitamin B-12, may be related to cognitive ageing but epidemiological evidence remains inconclusive. The aim of this study was to estimate the association of serum folate and vitamin B-12 concentrations with cognitive function in middle-aged and older adults from three Central and Eastern European populations. Men and women aged 45-69 at baseline participating in the Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) study were recruited in Krakow (Poland), Kaunas (Lithuania) and six urban centres in the Czech Republic. Tests of immediate and delayed recall, verbal fluency and letter search were administered at baseline and repeated in 2006-2008. Serum concentrations of biomarkers at baseline were measured in a sub-sample of participants. Associations of vitamin quartiles with baseline (n=4166) and follow-up (n=2739) cognitive domain-specific z-scores were estimated using multiple linear regression. After adjusting for confounders, folate was positively associated with letter search and vitamin B-12 with word recall in cross-sectional analyses. In prospective analyses, participants in the highest quartile of folate had higher verbal fluency (pcognitive domains in older Central and Eastern Europeans. These findings do not lend unequivocal support to potential importance of folate and vitamin B-12 status for cognitive function in older age. Long-term longitudinal studies and randomised trials are required before drawing conclusions on the role of these vitamins in cognitive decline. Copyright © 2016. Published by Elsevier Inc.

  13. Brief Report: Childhood Disintegrative Disorder as a Likely Manifestation of Vitamin B12 Deficiency

    Science.gov (United States)

    Malhotra, Savita; Subodh, B. N.; Parakh, Preeti; Lahariya, Sanjay

    2013-01-01

    Childhood disintegrative disorder is a rare disorder, characterized by regression of acquired skills after a period of normal development. The case of childhood disintegrative disorder presented here was found to have vitamin B12 deficiency and hyperhomocysteinemia on extensive evaluation to find a probable cause for regression. This case…

  14. Vitamin B12, folate, and homocysteine in depression: the Rotterdam Study

    NARCIS (Netherlands)

    H.W. Tiemeier (Henning); H.R. van Tuijl (Ruud); J. Meijer (John); A.J. Kiliaan (Amanda); M.M.B. Breteler (Monique); A. Hofman (Albert)

    2002-01-01

    textabstractOBJECTIVE: The associations of vitamin B(12), folate, and homocysteine with depression were examined in a population-based study. METHOD: The authors screened 3,884 elderly people for depressive symptoms. Subjects with positive screening results had psychiatric workups.

  15. Effects of divalent cations on vitamin B12 adsorption to brush borders of rat intestine

    International Nuclear Information System (INIS)

    Miyata, Satoru; Inada, Masami

    1976-01-01

    A brush border preparation from rat intestine was incubated with rat intrinsic factor-vitamin B 12 complex in 0.01M Tris-HCl buffer, pH 7.4. The 57 Co-B 12 uptake to brush borders was proportional to the amount of protein or to alkaline phosphatase activity in the preparations. The uptake increased with time of incubation. At 37 0 C, the uptake after incubation for 15 min. was 80-85% of that for one hr. The uptake at 4 0 C was approximately 70% of that at 37 0 C. There was no difference as a result of adding glucose to the incubation medium. The uptake was observed in the alkaline environment above pH 6.3. Maximum uptake occurred at pH 8.0. Brush borders washed with Krebs-Ringer bicarbonate buffer (pH 7.4) exhibited no difference in B 12 uptake, whether in the presence of absence of calcium ion. But brush borders washed with ethylenediaminetetraacetate exhibited no uptake when incubated in calcium-free medium. The uptake reached a maximum by addition of calcium ion at a concentration of 0.3 mM, and was not alter up to 10 mM. Addition of magnesium ion exhibited no uptake. Calcium-dependent B 12 uptake was markedly inhibited by manganese ion. Magnesium ion seemed to slightly inhibit the calcium-dependent uptake. (auth.)

  16. Expeditious synthesis of noble metal nanoparticles using Vitamin B12 under microwave irradiation

    Science.gov (United States)

    A greener synthesis protocol for noble nanometals is developed using vitamin B12 as a reducing and capping agent in conjunction with the use of microwaves. Successful assembly of nanoparticles or microparticles with varied shapes and sizes have been demonstrated. The synthesized ...

  17. Dual pathology as a result of spinal stenosis and vitamin B12 deficiency.

    Science.gov (United States)

    Patel, Mohammed Shakil; Rasul, Zurqa; Sell, Philip

    2011-12-01

    Vitamin B12 deficiency can confound the clinical assessment of patients presenting with features of spinal disorders. Speciality practice within spinal surgery may lead the clinician to a focus upon spinal explanations for symptoms and that belief may be reinforced by supporting imaging. In the presence of mainly sensory symptoms consideration and exclusion of non surgical causes needs to occur. This study aimed at identifying the prevalence of vitamin B12 deficiency; the presence of dual pathology on imaging performed; the implementation of replacement therapy and their subsequent clinical response as perceived by patients. This was performed through a retrospective review of patients presenting to specialist spine out-patient clinics over a 4-year period via access to pathology reports followed by a telephone survey. 457 patients were investigated of which 8.5% were vitamin B12 deficient. 70% of patients had repeat levels and 31% continued to be deficient. 26% of these patients were not placed on any supplemental therapy. 72% of patients on treatment had self perceived improved outcomes as compared with 55% not on treatment. 73% of patients underwent MRI/CT imaging. 59% of which had evidence of spinal stenosis. In older patients with sensory symptoms, the coexistence of B12 deficiency should be considered. Detection of deficiency with consequent treatment results in better global outcomes than no treatment. Unless the correct blood test is done, the pathology will remain undetected, and patients may continue with their primary symptoms despite high-risk spinal surgical procedures.

  18. Low-temperature heat capacity and thermodynamic functions of vitamin B12

    International Nuclear Information System (INIS)

    Knyazev, A.V.; Smirnova, N.N.; Plesovskikh, A.S.; Shushunov, A.N.; Knyazeva, S.S.

    2014-01-01

    Graphical abstract: - Highlights: • Temperature dependence of heat capacity of vitamin B 12 has been measured by precision adiabatic vacuum calorimetry. • The thermodynamic functions of the vitamin B 12 have been determined for the range from T → 0 to 343 K. • The character of heterodynamics of structure was detected. • The thermal stability of cyanocobalamin was studied by differential scanning calorimetry. - Abstract: In the present work temperature dependence of heat capacity of vitamin B 12 (cyanocobalamin) has been measured for the first time in the range from 6 to 343 K by precision adiabatic vacuum calorimetry. Based on the experimental data, the thermodynamic functions of the vitamin B 12 , namely, the heat capacity, enthalpy H°(T) − H°(0), entropy S°(T) − S°(0) and Gibbs function G°(T) − H°(0) have been determined for the range from T → 0 to 343 K. The value of the fractal dimension D in the function of multifractal generalization of Debye's theory of the heat capacity of solids was estimated and the character of heterodynamics of structure was detected. The thermal stability of cyanocobalamin was also studied by differential scanning calorimetry

  19. Total serum homocysteine as an indicator of vitamin B12 and folate status

    International Nuclear Information System (INIS)

    Chu, R.C.; Hall, C.A.

    1988-01-01

    Presented is a modification of an assay for total serum homocysteine (Hcy) in which the Hcy plus radioactive adenosine is converted enzymatically to labeled S-adenosylhomocysteine (AdoHcy). The modifications included a commerical source for the AdoHcy hydrolase, adenosine labeled with either 14 C or 3 H, and separation of the AdoHcy by thin layer chromatography. The assay was sensitive to 25 pmol. Hcy levels in sera from 18 controls ranged from 6.9 to 12.1 mumol/L with a mean of 9.1 and a SD of 1.5 mumol/L. The total serum Hcy was increased in vitamin B12 and folate deficiency. The level was high in congenital defects of vitamin B12 metabolism, blocking the methylation of Hcy regardless of the serum vitamin B12 levels, but was normal in the absence of tissue deficiency even if the serum vitamin B12 levels were low. The procedure has been found practical in two years of use and requires only 0.1 mL of serum

  20. A triple isotope technique for estimation of fat and vitamin B12 malabsorption in Chrohn's disease

    International Nuclear Information System (INIS)

    Pedersen, N.T.; Rannem, T.

    1991-01-01

    A test for simultaneous estimation of vitamin B 12 and fat absorption from stool samples was investigated in 25 patients with severe diarrhoea after operation for Chrohn's disease. 51 CrCl 3 was ingested as a non-absorbable marker, 58 Co-cyanocobalamin as vitamin B 12 tracer, and 14 C-triolein as lipid tracer. Faeces were collected separately for three days. Some stool-to-stool variation in the 58 Co/ 51 Cr and 14 C/ 51 Cr ratios was seen. When the 58 Co-B 12 and 14 C-triolein excretion was estimated in samples of the two stools with the highest activities of 51 Cr, the variations of the estimates were less than ±10% and ±15% of the doses ingested, respectively. 12 of the 25 patients were not able to collect faeces and urine quantitatively and separately. However, in all patients faeces with sufficient radioactivity for simultaneous estimation of faecal 58 Co-B 12 and 14 C-triolein excretion from stool samples were obtained. 16 refs., 3 figs., 1 tab

  1. Coenzyme B12 model studies: Equilibrium constants for the pH ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 114; Issue 1. Coenzyme B12 model studies: Equilibrium constants for the H-dependent axial ligation of benzyl(aquo)cobaloxime by various N- and S-donor ligands. D Sudarshan Reddy N Ravi Kumar Reddy V Sridhar S Satyanarayana. Inorganic and Analytical ...

  2. 17 CFR 240.3b-12 - Definition of OTC derivatives dealer.

    Science.gov (United States)

    2010-04-01

    ... to options, forwards, futures, swap agreements, or collars involving currencies, interest or other... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Definition of OTC derivatives... Securities Exchange Act of 1934 Definitions § 240.3b-12 Definition of OTC derivatives dealer. The term OTC...

  3. High prevalence of suboptimal vitamin B12 status in young adult women of South Asian and European ethnicity.

    Science.gov (United States)

    Quay, Teo A W; Schroder, Theresa H; Jeruszka-Bielak, Marta; Li, Wangyang; Devlin, Angela M; Barr, Susan I; Lamers, Yvonne

    2015-12-01

    Suboptimal vitamin B12 (B12) status has been associated with an increased risk of congenital anomalies, preterm birth, and childhood insulin resistance. South Asians - Canada's largest minority group - and women of reproductive age are vulnerable to B12 deficiency. This study aimed to assess the prevalence of and factors associated with B12 deficiency and suboptimal B12 status in a convenience sample of young adult women of South Asian and European descent in Metro Vancouver. We measured serum B12, holotranscobalamin, plasma methylmalonic acid, red blood cell and plasma folate, and hematologic parameters in 206 nonpregnant, healthy women aged 19-35 years. Categorization for B12 status adhered to serum B12 cutoffs for deficiency (women is higher than in the general Canadian population. In light of maternal and fetal health risks associated with B12 inadequacy in early-pregnancy, practitioners should consider monitoring B12 status before and during early pregnancy, especially in immigrants and women with low dietary B12 intakes including non-users of vitamin supplements.

  4. Low levels of vitamin B12 can persist in the early resettlement of refugees: symptoms, screening and monitoring.

    Science.gov (United States)

    Benson, Jill; Phillips, Christine; Kay, Margaret; Hanifi, Hoda; Giri, Gauri; Leahy, Catherine; Lorimer, Michelle

    2015-09-01

    Many refugees have vitamin B12 (B12) deficiency. It has been assumed that deficiency would be predictable from macrocytosis or symptoms, and borderline levels would improve after a period of resettlement in countries rich with animal-source foods. We explored B12 levels and symptoms soon after the refugees' arrival and 4-8 months after settlement in Australia. Newly arrived refugees aged >18 years (n = 136) were tested for vitamin B12 and haematological indices. They also completed a language-validated questionnaire, which they repeated 4-8 months after arrival. B12 levels were reassessed in patients with levels ≤240 pmol at baseline. We found that 21 participants (15%) had low levels of B12 
(≤150 pmol/L) and 65 (48%) had borderline B12 levels 
(151-240 pmol/L). There was no relationship between B12 level and mean corpuscular volume, ferritin or symptoms. Borderline B12 levels persisted in 64% of participants at follow-up and deficiency developed in 11%. B12 levels cannot be predicted from macrocytosis or symptoms, and may not 'self-correct' after resettlement. Health assessments for newly arrived refugees should include B12 measurement and those with borderline levels should be followed up.

  5. Treatment of depression: time to consider folic acid and vitamin B12.

    Science.gov (United States)

    Coppen, Alec; Bolander-Gouaille, Christina

    2005-01-01

    We review the findings in major depression of a low plasma and particularly red cell folate, but also of low vitamin B12 status. Both low folate and low vitamin B12 status have been found in studies of depressive patients, and an association between depression and low levels of the two vitamins is found in studies of the general population. Low plasma or serum folate has also been found in patients with recurrent mood disorders treated by lithium. A link between depression and low folate has similarly been found in patients with alcoholism. It is interesting to note that Hong Kong and Taiwan populations with traditional Chinese diets (rich in folate), including patients with major depression, have high serum folate concentrations. However, these countries have very low life time rates of major depression. Low folate levels are furthermore linked to a poor response to antidepressants, and treatment with folic acid is shown to improve response to antidepressants. A recent study also suggests that high vitamin B12 status may be associated with better treatment outcome. Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional marker of both folate and vitamin B12 deficiency. Increased homocysteine levels are found in depressive patients. In a large population study from Norway increased plasma homocysteine was associated with increased risk of depression but not anxiety. There is now substantial evidence of a common decrease in serum/red blood cell folate, serum vitamin B12 and an increase in plasma homocysteine in depression. Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is shown to be overrepresented among depressive patients, which strengthens the association. On the basis of current data, we suggest that oral doses of both folic acid (800 microg daily

  6. Antibodies to H2a and H2b histones from the sera of HIV-infected patients catalyze site-specific degradation of these histones.

    Science.gov (United States)

    Baranova, Svetlana V; Dmitrienok, Pavel S; Ivanisenko, Nikita V; Buneva, Valentina N; Nevinsky, Georgy A

    2017-06-01

    major cleavage site of H2a are located in the disordered N-terminal region interacting with DNA. According to the crystal structure of the nucleosome core particle, all identified cleavage sites are expected to affect H2a and H2b folding, nucleosome assembly, and binding of H2a and H2b with DNA. The existence of H2a and H2b hydrolyzing abzymes may be very important for the further understanding of unknown possibilities of immune systems and biological functions of antibodies.

  7. Comparative genomic analyses of nickel, cobalt and vitamin B12 utilization

    Directory of Open Access Journals (Sweden)

    Gelfand Mikhail S

    2009-02-01

    Full Text Available Abstract Background Nickel (Ni and cobalt (Co are trace elements required for a variety of biological processes. Ni is directly coordinated by proteins, whereas Co is mainly used as a component of vitamin B12. Although a number of Ni and Co-dependent enzymes have been characterized, systematic evolutionary analyses of utilization of these metals are limited. Results We carried out comparative genomic analyses to examine occurrence and evolutionary dynamics of the use of Ni and Co at the level of (i transport systems, and (ii metalloproteomes. Our data show that both metals are widely used in bacteria and archaea. Cbi/NikMNQO is the most common prokaryotic Ni/Co transporter, while Ni-dependent urease and Ni-Fe hydrogenase, and B12-dependent methionine synthase (MetH, ribonucleotide reductase and methylmalonyl-CoA mutase are the most widespread metalloproteins for Ni and Co, respectively. Occurrence of other metalloenzymes showed a mosaic distribution and a new B12-dependent protein family was predicted. Deltaproteobacteria and Methanosarcina generally have larger Ni- and Co-dependent proteomes. On the other hand, utilization of these two metals is limited in eukaryotes, and very few of these organisms utilize both of them. The Ni-utilizing eukaryotes are mostly fungi (except saccharomycotina and plants, whereas most B12-utilizing organisms are animals. The NiCoT transporter family is the most widespread eukaryotic Ni transporter, and eukaryotic urease and MetH are the most common Ni- and B12-dependent enzymes, respectively. Finally, investigation of environmental and other conditions and identity of organisms that show dependence on Ni or Co revealed that host-associated organisms (particularly obligate intracellular parasites and endosymbionts have a tendency for loss of Ni/Co utilization. Conclusion Our data provide information on the evolutionary dynamics of Ni and Co utilization and highlight widespread use of these metals in the three

  8. Influenza human monoclonal antibody 1F1 interacts with three major antigenic sites and residues mediating human receptor specificity in H1N1 viruses.

    Directory of Open Access Journals (Sweden)

    Tshidi Tsibane

    Full Text Available Most monoclonal antibodies (mAbs to the influenza A virus hemagglutinin (HA head domain exhibit very limited breadth of inhibitory activity due to antigenic drift in field strains. However, mAb 1F1, isolated from a 1918 influenza pandemic survivor, inhibits select human H1 viruses (1918, 1943, 1947, and 1977 isolates. The crystal structure of 1F1 in complex with the 1918 HA shows that 1F1 contacts residues that are classically defined as belonging to three distinct antigenic sites, Sa, Sb and Ca(2. The 1F1 heavy chain also reaches into the receptor binding site (RBS and interacts with residues that contact sialoglycan receptors and determine HA receptor specificity. The 1F1 epitope is remarkably similar to the previously described murine HC63 H3 epitope, despite significant sequence differences between H1 and H3 HAs. Both antibodies potently inhibit receptor binding, but only HC63 can block the pH-induced conformational changes in HA that drive membrane fusion. Contacts within the RBS suggested that 1F1 may be sensitive to changes that alter HA receptor binding activity. Affinity assays confirmed that sequence changes that switch the HA to avian receptor specificity affect binding of 1F1 and a mAb possessing a closely related heavy chain, 1I20. To characterize 1F1 cross-reactivity, additional escape mutant selection and site-directed mutagenesis were performed. Residues 190 and 227 in the 1F1 epitope were found to be critical for 1F1 reactivity towards 1918, 1943 and 1977 HAs, as well as for 1I20 reactivity towards the 1918 HA. Therefore, 1F1 heavy-chain interactions with conserved RBS residues likely contribute to its ability to inhibit divergent HAs.

  9. A blue corrinoid from partial degradation of vitamin B12 in aqueous bicarbonate: spectra, structure, and interaction with proteins of B12 transport.

    Science.gov (United States)

    Fedosov, Sergey N; Ruetz, Markus; Gruber, Karl; Fedosova, Natalya U; Kräutler, Bernhard

    2011-09-20

    Cobalamin (Cbl) is a complex cofactor produced only by bacteria but used by all animals and humans. Cyanocobalamin (vitamin B(12), CNCbl) is one commonly isolated form of cobalamin. B(12) belongs to a large group of corrinoids, which are characterized by a distinct red color conferred by the system of conjugated double bonds of the corrin ring retaining a Co(III) ion. A unique blue Cbl derivative was produced by hydrolysis of CNCbl in a weakly alkaline aqueous solution of bicarbonate. This corrinoid was purified and isolated as dark blue crystals. Its spectroscopic analysis and X-ray crystallography revealed B-ring opening with formation of 7,8-seco-cyanocobalamin (7,8-sCNCbl). The unprecedented structural change was caused by cleavage of the peripheral C-C bond between saturated carbons 7 and 8 of the corrin macrocycle accompanied by formation of a C═C bond at C7 and a carbonyl group at C8. Additionally, the C-amide was hydrolyzed to a carboxylic acid. The extended conjugation of the π-system caused a considerable red shift of the absorbance spectrum. Formation and degradation of 7,8-sCNCbl were analyzed qualitatively. Its interaction with the proteins of mammalian Cbl transport revealed both a slow binding kinetics and a low overall affinity. The binding data were compared to those of other monocarboxylic derivatives and agreed with the earlier proposed scheme for two-step ligand recognition. The obtained results are consistent with the structural models of 7,8-sCNCbl and the transport proteins intrinsic factor and transcobalamin. Potential applications of the novel derivative for drug conjugation are discussed. © 2011 American Chemical Society

  10. Novel Prostate Specific Antigen plastic antibody designed with charged binding sites for an improved protein binding and its application in a biosensor of potentiometric transduction

    International Nuclear Information System (INIS)

    Rebelo, Tânia S.C.R.; Santos, C.; Costa-Rodrigues, J.; Fernandes, M.H.; Noronha, João P.; Sales, M. Goreti F.

    2014-01-01

    Graphical abstract: EF13-201, Novel Prostate Specific Antigen plastic antibody designed with charged binding sites for an improved protein binding and its application in a biosensor of potentiometric transduction. - Abstract: This work shows that the synthesis of protein plastic antibodies tailored with selected charged monomers around the binding site enhances protein binding. These charged receptor sites are placed over a neutral polymeric matrix, thus inducing a suitable orientation the protein reception to its site. This is confirmed by preparing control materials with neutral monomers and also with non-imprinted template. This concept has been applied here to Prostate Specific Antigen (PSA), the protein of choice for screening prostate cancer throughout the population, with serum levels >10 ng/mL pointing out a high probability of associated cancer. Protein Imprinted Materials with charged binding sites (C/PIM) have been produced by surface imprinting over graphene layers to which the protein was first covalently attached. Vinylbenzyl(trimethylammonium chloride) and vinyl benzoate were introduced as charged monomers labelling the binding site and were allowed to self-organize around the protein. The subsequent polymerization was made by radical polymerization of vinylbenzene. Neutral PIM (N/PIM) prepared without oriented charges and non imprinted materials (NIM) obtained without template were used as controls. These materials were used to develop simple and inexpensive potentiometric sensor for PSA. They were included as ionophores in plasticized PVC membranes, and tested over electrodes of solid or liquid conductive contacts, made of conductive carbon over a syringe or of inner reference solution over micropipette tips. The electrodes with charged monomers showed a more stable and sensitive response, with an average slope of -44.2 mV/decade and a detection limit of 5.8 × 10 −11 mol/L (2 ng/mL). The corresponding non-imprinted sensors showed lower

  11. Monoclonal antibodies and cancer

    International Nuclear Information System (INIS)

    Haisma, H.J.

    1987-01-01

    The usefulness of radiolabeled monoclonal antibodies for imaging and treatment of human (ovarian) cancer was investigated. A review of tumor imaging with monoclonal antibodies is presented. Special attention is given to factors that influence the localization of the antibodies in tumors, isotope choice and methods of radiolabeling of the monoclonal antibodies. Two monoclonal antibodies, OC125 and OV-TL3, with high specificity for human epithelial ovarian cancer are characterized. A simple radio-iodination technique was developed for clinical application of the monoclonal antibodies. The behavior of monoclonal antibodies in human tumor xenograft systems and in man are described. Imaging of tumors is complicated because of high background levels of radioactivity in other sites than the tumor, especially in the bloodpool. A technique was developed to improve imaging of human tumor xenographs in nude mice, using subtraction of a specific and a non-specific antibody, radiolabeled with 111 In, 67 Ga and 131 I. To investigate the capability of the two monoclonal antibodies, to specifically localize in human ovarian carcinomas, distribution studies in mice bearing human ovarian carcinoma xenografts were performed. One of the antibodies, OC125, was used for distribution studies in ovarian cancer patients. OC125 was used because of availability and approval to use this antibody in patients. The same antibody was used to investigate the usefulness of radioimmunoimaging in ovarian cancer patients. The interaction of injected radiolabeled antibody OC125 with circulating antigen and an assay to measure the antibody response in ovarian cancer patients after injection of the antibody is described. 265 refs.; 30 figs.; 19 tabs

  12. Antigenic Fingerprinting following Primary RSV Infection in Young Children Identifies Novel Antigenic Sites and Reveals Unlinked Evolution of Human Antibody Repertoires to Fusion and Attachment Glycoproteins.

    Directory of Open Access Journals (Sweden)

    Sandra Fuentes

    2016-04-01

    Full Text Available Respiratory Syncytial Virus (RSV is the major cause of pneumonia among infants. Here we elucidated the antibody repertoire following primary RSV infection and traced its evolution through adolescence and adulthood. Whole genome-fragment phage display libraries (GFPDL expressing linear and conformational epitopes in the RSV fusion protein (F and attachment protein (G were used for unbiased epitope profiling of infant sera prior to and following RSV infection. F-GFPDL analyses demonstrated modest changes in the anti-F epitope repertoires post-RSV infection, while G-GFPDL analyses revealed 100-fold increase in number of bound phages. The G-reactive epitopes spanned the N- and C-terminus of the G ectodomain, along with increased reactivity to the central conserved domain (CCD. Panels of F and G antigenic sites were synthesized to evaluate sera from young children (<2 yr, adolescents (14-18 yr and adults (30-45 yr in SPR real-time kinetics assays. A steady increase in RSV-F epitope repertoires from young children to adults was observed using peptides and F proteins. Importantly, several novel epitopes were identified in pre-fusion F and an immunodominant epitope in the F-p27. In all age groups, antibody binding to pre-fusion F was 2-3 folds higher than to post-fusion form. For RSV-G, antibody responses were high following early RSV infection in children, but declined significantly in adults, using either G proteins or peptides. This study identified unlinked evolution of anti-F and anti G responses and supportive evidence for immune pressure driven evolution of RSV-G. These findings could help development of effective countermeasures including vaccines.

  13. The impact of vegan diet on B-12 status in healthy omnivores: five-year prospective study.

    Science.gov (United States)

    Mądry, Edyta; Lisowska, Aleksandra; Grebowiec, Philip; Walkowiak, Jarosław

    2012-04-02

    There are no long-term prospective studies assessing the impact of the vegan diet on vitamin B-12 (B-12) status. Many vegans take B-12 supplements irregularly or refuse to adopt them at all, considering them to be "unnatural" products. The use of B-12 fortified food may be an alternative. Therefore, we aimed to estimate the long-term effect of a vegan diet on serum B-12 concentrations in healthy omnivore adults, comparing the influence of natural products consumption and B-12 fortified food. A five year prospective study was carried out comprising 20 omnivore healthy adult subjects, who moved to strict vegan diet for 5 years. Ten volunteers followed vegan diet based entirely on natural products, while the remaining ten subjects consumed food fortified in B-12. In all subjects serum vitamin B-12 concentration was determined before and 6, 12, 24 and 60 months after the implementation of the diet. A significant decrease (p vegan diet. However, observed changes were in fact limited to the subgroup consuming exclusively natural products (p vegan diet is associated with the risk of vitamin B-12 deficiency. B-12 fortified products might constitute a valuable alternative in vegans refusing to take vitamin supplements.

  14. Impact of cathepsin B-sensitive triggers and hydrophilic linkers on in vitro efficacy of novel site-specific antibody-drug conjugates.

    Science.gov (United States)

    Bryden, Francesca; Martin, Camille; Letast, Stéphanie; Lles, Eva; Viéitez-Villemin, Inmaculada; Rousseau, Anaïs; Colas, Cyril; Brachet-Botineau, Marie; Allard-Vannier, Emilie; Larbouret, Christel; Viaud-Massuard, Marie-Claude; Joubert, Nicolas

    2018-03-14

    Herein we describe the synthesis and evaluation of four novel HER2-targeting, cathepsin B-sensitive antibody-drug conjugates bearing a monomethylauristatin E (MMAE) cytotoxic payload, constructed via the conjugation of cleavable linkers to trastuzumab using a site-specific bioconjugation methodology. These linkers vary by both cleavable trigger motif and hydrophilicity, containing one of two cathepsin B sensitive dipeptides (Val-Cit and Val-Ala), and engendered with either hydrophilic or hydrophobic character via application of a PEG 12 spacer. Through evaluation of physical properties, in vitro cytotoxicity, and receptor affinity of the resulting antibody-drug conjugates (ADCs), we have demonstrated that while both dipeptide triggers are effective, the increased hydrophobicity of the Val-Ala pair limits its utility within this type of linker. In addition, while PEGylation augments linker hydrophilicity, this change does not translate to more favourable ADC hydrophilicity or potency. While all described structures demonstrated excellent and similar in vitro cytotoxicity, the ADC with the ValCitPABMMAE linker shows the most promising combination of in vitro potency, structural homogeneity, and hydrophilicity, warranting further evaluation into its therapeutic potential.

  15. Antimitochondrial antibody

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003529.htm Antimitochondrial antibody To use the sharing features on this page, please enable JavaScript. Antimitochondrial antibodies (AMA) are substances ( antibodies ) that form against mitochondria. ...

  16. Vitamina B12, Acido Fólico y Función Mental en Adultos Mayores

    OpenAIRE

    Meertens-R, Lesbia; Solano-R, Liseti

    2005-01-01

    Los adultos mayores constituyen un grupo de población vulnerable a cuadros de deficiencias de nutrientes específicos como la vitamina B12 y el ácido fólico, íntimamente ligados al deterioro de las funciones mentales, en especial, del área cognitiva. El objetivo de este estudio fue determinar indicadores del estado de vitamina B12 y ácido fólico y asociarlos a la evaluación de la función mental de 53 adultos mayores de 60 años de edad, residenciados en un hogar geriátrico. Se evaluó consumo di...

  17. Radioisotope dilution technique for determination of vitamin B12 in foods

    International Nuclear Information System (INIS)

    Casey, P.J.; Speckman, K.R.; Ebert, F.J.; Hobbs, W.E.

    1982-01-01

    A radioisotope dilution (RID) method for the determination of vitamin B 12 is presented. The method combines a standard extraction procedure (AOAC 43.108, 12th ed.) with a commercially available RID assay kit. The method was evaluated on a wide range of fortified and unfortified food products. Recovery studies on both groups yielded average recoveries of 98.1 and 95.8%, respectively. Reproducibility data generated from replicate analysis on both groups gave a relative standard deviation of 6.9% for the fortified group and 9.2% for the unfortified group. For the samples studied, the mean vitamin B 12 content determined by the RID method was 8.01 μ/100 g vs a mean of 7.54 μg/100 g by the AOAC microbiological method; the correlation coefficient was r = 0.983

  18. An evaluation of commercial radioisotope methods for the determination of folate and vitamin B12

    International Nuclear Information System (INIS)

    Dawson, D.W.

    1980-01-01

    Five commercial kits for the determination of folate and six kits for the determination of vitamin B 12 were investigated. Their performance has been compared with microbiological methods for the two vitamins and with a non-commercial radioisotopic method for B 12 . The results show the importance of the determination of the reference range for an individual laboratory for each method. The precision of the kits varied appreciably, as did their performance using specimens from patients with different haematological disorders. In particular, certain kits failed to detect all patients with pernicious anaemia. The relative accuracy of the kits was assessed. Various factors which should be taken into account in the final selection of a satisfactory kit are discussed. (author)

  19. Phylogenetic analysis of vitamin B12-related metabolism in Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Douglas B. Young

    2015-03-01

    Full Text Available Comparison of genome sequences from clinical isolates of Mycobacterium tuberculosis with phylogenetically-related pathogens Mycobacterium marinum, Mycobacterium kansasii and Mycobacterium leprae reveals diversity amongst genes associated with vitamin B12-related metabolism. Diversity is generated by gene deletion events, differential acquisition of genes by horizontal transfer, and single nucleotide polymorphisms with predicted impact on protein function and transcriptional regulation. Differences in the B12 synthesis pathway, methionine biosynthesis, fatty acid catabolism, and DNA repair and replication are consistent with adaptations to different environmental niches and pathogenic lifestyles. While there is no evidence of further gene acquisition during expansion of the M. tuberculosis complex, the emergence of other forms of genetic diversity provides insights into continuing host-pathogen co-evolution and has the potential to identify novel targets for disease intervention.

  20. Synthesis and crystal structure of Pb(Bipy)(DMFA)B12H12

    International Nuclear Information System (INIS)

    Lagun, V.L.; Solntsev, K.A.; Katser, S.B.; Orlova, A.M.; Kuznetsov, N.T.

    1994-01-01

    Lead complex with B 12 H 12 2- anion and neutral ligands -2,2' -bipyridine (Bipy) and dimethylformamide (DMFA) has been prepared by Pb(Bipy) B 12 H 12 recrystallization from mixed solvent DMFA - benzene (1:1). The complex prepared has been studied by the methods of IR spectroscopy, element and X-ray diffraction analyses. Parameters of monoclinic cell are as follows: 1 = 9.583(2), b = 16.958 (4), c = 18.685 (3) A; β = 105.65 (2), V = 2924 (1) A 3 , Z =4; sp.gr. P2 1 /c. The structure consists of dimer units. Pb-B distance is within 3.23-3.71 (3) A. 5 refs.; 2 figs.; 2 tabs

  1. Synthesis and crystal structure of Pb(Bipy)2B12H12

    International Nuclear Information System (INIS)

    Lagun, V.L.; Orlova, A.M.; Katser, S.B.; Solntsev, K.A.; Kuznetsov, N.T.

    1994-01-01

    Lead complex with B 12 H 12 2- anion and 2,2' bipyridine-lead(2) dodecahydro-closo-dodecaborate di(2,2' bipyridine) is synthesized and characterized by IF, UV and NMR spectrography methods. According to roentgen-structural analysis the crystals belong to monoclinic syngony, sp.gr. C2/m,a=17.872(4), b=18.672(5), c=9.228(7)A, β=109.11(4), V=2910(2)A 3 , Z=4. The structure consists of Pb 2 (Bipy) 4 (B 12 H 12 ) 2 dimeric units. The Pb-B distances are within the limits of 3.313-3.514A. 11 refs.; 2 figs.; 2 tabs

  2. Diffusion of Vitamin B12 Across a Mesoporous Metal Organic Framework

    Directory of Open Access Journals (Sweden)

    Veronica Valencia

    2013-01-01

    Full Text Available We measure the rate of uptake and the rate of release of a Vitamin B12 solution (dissolved in water at 2 different temperatures (room temperature and 37°C by the mesoporous metal organic framework TbMOF-100 at 1-hour intervals using a spectrophotometer. Using the Beer-Lambert law, we calculate the concentration of the stock solution based on the absorbance values obtained with the spectrophotometer. These values allow for the quantification of the initial rate of uptake and the rate of uptake at a random incubation time of the Vitamin B12 by the TbMOF-100. We also calculate the value of the coefficient of diffusion for this 2-phase system using Fick’s laws of diffusion.

  3. Vitamin B12 in metformin-treated diabetic patients: a cross-sectional study in Brazil Vitamina B12 em pacientes diabéticos usando metformina: um corte transversal no Brasil

    OpenAIRE

    Monique Nervo; Adriano Lubini; Fabiana Viegas Raimundo; Gustavo Adolpho Moreira Faulhaber; Carine Leite; Leonardo Moura Fischer; Tania Weber Furlanetto

    2011-01-01

    OBJECTIVE: The objective of this study was to evaluate the presence of vitamin B12 deficiency and the factors associated with serum vitamin B12 levels in a sample of metformin-treated Brazilian diabetic patients. METHOD: Cross-sectional study. RESULTS: 144 patients were included. Serum vitamin B12 levels were low (< 125 pmol/L) in 10 patients (6.9%) and possibly low (125 - 250 pmol/L) in 53 patients (36.8%). Serum vitamin B12 levels were negatively associated with age (B = -3.17; β= -0.1...

  4. A simple and fast detection method for bovine milk residues in foods: a 2-site monoclonal antibody immunochromatography assay.

    Science.gov (United States)

    Xuli, Wu; Weiyi, He; Ji, Kunmei; Wenpu, Wan; Dongsheng, Hu; Hui, Wu; Xinpin, Luo; Zhigang, Liu

    2013-03-01

    The ingredient declaration on food labels assumes paramount importance in the protection of food-allergic consumers. China has not implemented Food allergen labeling. A gold immunochromatography assay (GICA) was developed using 2 monoclonal antibodies (mAb) against the milk allergen β-lactoglobulin in this study. The GICA was specific for pure milk samples with a sensitivity of 0.2 ng/mL. Milk protein traces extracted from 110 food products were detected by this method. The labels of 106 were confirmed by our GICA method: 57 food samples originally labeled as containing milk were positive for β-lactoglobulin and 49 food samples labeled as not containing milk were negative for β-lactoglobulin. However, 3 food samples falsely labeled as containing milk were found to contain no β-lactoglobulin whereas 1 food sample labeled as not containing milk actually contained β-lactoglobulin. First, these negatives could be because of the addition of a casein fraction. Second, some countries demand that food manufacturers label all ingredients derived from milk as "containing milk" even though the ingredients contain no detectable milk protein by any method. Our GICA method could thus provide a fast and simple method for semiquantitatation of β-lactoglobulin in foods. The present method provides a fast, simple, semiquantitative method for the determination of milk allergens in foods. © 2013 Institute of Food Technologists®

  5. Ultrafast electronic relaxation of excited state vitamin B12 in the gas phase

    International Nuclear Information System (INIS)

    Shafizadeh, Niloufar; Poisson, Lionel; Soep, Benoit

    2008-01-01

    The time evolution of electronically excited vitamin B 12 (cyanocobalamin) has been observed for the first time in the gas phase. It reveals an ultrafast decay to a state corresponding to metal excitation. This decay is interpreted as resulting from a ring to metal electron transfer. This opens the observation of the excited state of other complex biomimetic systems in the gas phase, the key to the characterisation of their complex evolution through excited electronic states

  6. Quantifying the Electrocatalytic Turnover of Vitamin B12-Mediated Dehalogenation on Single Soft Nanoparticles.

    Science.gov (United States)

    Cheng, Wei; Compton, Richard G

    2016-02-12

    We report the electrocatalytic dehalogenation of trichloroethylene (TCE) by single soft nanoparticles in the form of Vitamin B12 -containing droplets. We quantify the turnover number of the catalytic reaction at the single soft nanoparticle level. The kinetic data shows that the binding of TCE with the electro-reduced vitamin in the Co(I) oxidation state is chemically reversible. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Long term treatment with metformin in patients with type 2 diabetes and vitamin B 12

    Directory of Open Access Journals (Sweden)

    Yu V Pankratova

    2012-12-01

    Full Text Available Реферат по статье: De Jager J, Kooy A, Lehert P, Wulffelé MG, van der Kolk J, Bets D, Verburg J, Donker AJ, Stehouwer CD. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010 May 20;340:c2181.

  8. C. elegans MRP-5 Exports Vitamin B12 from Mother to Offspring to Support Embryonic Development.

    Science.gov (United States)

    Na, Huimin; Ponomarova, Olga; Giese, Gabrielle E; Walhout, Albertha J M

    2018-03-20

    Vitamin B12 functions as a cofactor for methionine synthase to produce the anabolic methyl donor S-adenosylmethionine (SAM) and for methylmalonyl-CoA mutase to catabolize the short-chain fatty acid propionate. In the nematode Caenorhabditis elegans, maternally supplied vitamin B12 is required for the development of offspring. However, the mechanism for exporting vitamin B12 from the mother to the offspring is not yet known. Here, we use RNAi of more than 200 transporters with a vitamin B12-sensor transgene to identify the ABC transporter MRP-5 as a candidate vitamin B12 exporter. We show that the injection of vitamin B12 into the gonad of mrp-5 deficient mothers rescues embryonic lethality in the offspring. Altogether, our findings identify a maternal mechanism for the transit of an essential vitamin to support the development of the next generation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Mielopatia por deficiência de vitamina B12 apresentando-se como mielite transversa

    Directory of Open Access Journals (Sweden)

    Vasconcellos Luiz Felipe Rocha

    2002-01-01

    Full Text Available As manifestações neurológicas associadas à deficiência de vitamina B12 incluem polineuropatia, mielopatia, demência e neuropatia óptica. O diagnóstico laboratorial é feito através da dosagem sérica de cianocobalamina ou homocisteína e da excreção urinária de ácido metilmalônico. No estudo anatomopatológico observa-se na microscopia a destruição da mielina e de axônios vistos na substância branca. A região mais comumente afetada é o cordão posterior cervical e/ou torácico. O acometimento da coluna lateral é raro, ocorrendo em casos graves e avançados. O tratamento consiste na reposição de vitamina B12 e a resposta depende da gravidade do quadro e do tempo transcorrido entre o inicio dos sintomas e inicio do tratamento. Relatamos o caso de um paciente que apresentou, como manifestação de deficiência de vitamina B12, mielite transversa. O estudo morfológico da medula demonstrou comprometimento dos tractos cortico-espinhais lateral e anterior, da coluna dorsal e ainda do tracto espino-talâmico.

  10. Coenzyme B12 synthesis as a baseline to study metabolite contribution of animal microbiota.

    Science.gov (United States)

    Danchin, Antoine; Braham, Sherazade

    2017-07-01

    Microbial communities thrive in a number of environments. Exploration of their microbiomes - their global genome - may reveal metabolic features that contribute to the development and welfare of their hosts, or chemical cleansing of environments. Yet we often lack final demonstration of their causal role in features of interest. The reason is that we do not have proper baselines that we could use to monitor how microbiota cope with key metabolites in the hosting environment. Here, focusing on animal gut microbiota, we describe the fate of cobalamins - metabolites of the B12 coenzyme family - that are essential for animals but synthesized only by prokaryotes. Microbiota produce the vitamin used in a variety of animals (and in algae). Coprophagy plays a role in its management. For coprophobic man, preliminary observations suggest that the gut microbial production of vitamin B12 plays only a limited role. By contrast, the vitamin is key for structuring microbiota. This implies that it is freely available in the environment. This can only result from lysis of the microbes that make it. A consequence for biotechnology applications is that, if valuable for their host, B12-producing microbes should be sensitive to bacteriophages and colicins, or make spores. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  11. Possible Involvement of Hydrosulfide in B12-Dependent Methyl Group Transfer

    Directory of Open Access Journals (Sweden)

    John I. Toohey

    2017-04-01

    Full Text Available Evidence from several fields of investigation lead to the hypothesis that the sulfur atom is involved in vitamin B12-dependent methyl group transfer. To compile the evidence, it is necessary to briefly review the following fields: methylation, the new field of sulfane sulfur/hydrogen sulfide (S°/H2S, hydrosulfide derivatives of cobalamins, autoxidation of hydrosulfide radical, radical S-adenosylmethionine methyl transfer (RSMT, and methionine synthase (MS. Then, new reaction mechanisms for B12-dependent methyl group transfer are proposed; the mechanisms are facile and overcome difficulties that existed in previously-accepted mechanisms. Finally, the theory is applied to the effect of S°/H2S in nerve tissue involving the “hypomethylation theory” that was proposed 50 years ago to explain the neuropathology resulting from deficiency of vitamin B12 or folic acid. The conclusions are consistent with emerging evidence that sulfane sulfur/hydrogen sulfide may be beneficial in treating Alzheimer’s disease.

  12. Crosstalk between Vitamins A, B12, D, K, C, and E Status and Arterial Stiffness

    Science.gov (United States)

    Luca, Constantin Tudor

    2017-01-01

    Arterial stiffness is associated with cardiovascular risk, morbidity, and mortality. The present paper reviews the main vitamins related to arterial stiffness and enabling destiffening, their mechanisms of action, providing a brief description of the latest studies in the area, and their implications for primary cardiovascular prevention, clinical practice, and therapy. Despite inconsistent evidence for destiffening induced by vitamin supplementation in several randomized clinical trials, positive results were obtained in specific populations. The main mechanisms are related to antiatherogenic effects, improvement of endothelial function (vitamins A, C, D, and E) and metabolic profile (vitamins A, B12, C, D, and K), inhibition of the renin-angiotensin-aldosterone system (vitamin D), anti-inflammatory (vitamins A, D, E, and K) and antioxidant effects (vitamins A, C, and E), decrease of homocysteine level (vitamin B12), and reversing calcification of arteries (vitamin K). Vitamins A, B12, C, D, E, and K status is important in evaluating cardiovascular risk, and vitamin supplementation may be an effective, individualized, and inexpensive destiffening therapy. PMID:28167849

  13. Disposable pencil graphite electrode modified with peptide nanotubes for Vitamin B12 analysis

    International Nuclear Information System (INIS)

    Pala, Betül Bozdoğan; Vural, Tayfun; Kuralay, Filiz; Çırak, Tamer; Bolat, Gülçin; Abacı, Serdar; Denkbaş, Emir Baki

    2014-01-01

    In this study, peptide nanostructures from diphenylalanine were synthesized in various solvents with various polarities and characterized with Scanning Electron Microscopy (SEM) and Powder X-ray Diffraction (PXRD) techniques. Formation of peptide nanofibrils, nanovesicles, nanoribbons, and nanotubes was observed in different solvent mediums. In order to investigate the effects of peptide nanotubes (PNT) on electrochemical behavior of disposable pencil graphite electrodes (PGE), electrode surfaces were modified with fabricated peptide nanotubes. Electrochemical activity of the pencil graphite electrode was increased with the deposition of PNTs on the surface. The effects of the solvent type, the peptide nanotube concentration, and the passive adsorption time of peptide nanotubes on pencil graphite electrode were studied. For further electrochemical studies, electrodes were modified for 30 min by immobilizing PNTs, which were prepared in water at 6 mg/mL concentration. Vitamin B 12 analyses were performed by the Square Wave (SW) voltammetry method using modified PGEs. The obtained data showed linearity over the range of 0.2 μM and 9.50 μM Vitamin B 12 concentration with high sensitivity. Results showed that PNT modified PGEs were highly simple, fast, cost effective, and feasible for the electro-analytical determination of Vitamin B 12 in real samples.

  14. Low vitamin B12 levels among newly-arrived refugees from Bhutan, Iran and Afghanistan: a multicentre Australian study.

    Directory of Open Access Journals (Sweden)

    Jill Benson

    Full Text Available BACKGROUND: Vitamin B12 deficiency is prevalent in many countries of origin of refugees. Using a threshold of 5% above which a prevalence of low Vitamin B12 is indicative of a population health problem, we hypothesised that Vitamin B12 deficiency exceeds this threshold among newly-arrived refugees resettling in Australia, and is higher among women due to their increased risk of food insecurity. This paper reports Vitamin B12 levels in a large cohort of newly arrived refugees in five Australian states and territories. METHODS: In a cross-sectional descriptive study, we collected Vitamin B12, folate and haematological indices on all refugees (n = 916; response rate 94% of eligible population who had been in Australia for less than one year, and attended one of the collaborating health services between July 2010 and July 2011. RESULTS: 16.5% of participants had Vitamin B12 deficiency (<150 pmol/L. One-third of participants from Iran and Bhutan, and one-quarter of participants from Afghanistan had Vitamin B12 deficiency. Contrary to our hypothesis, low Vitamin B12 levels were more prevalent in males than females. A higher prevalence of low Vitamin B12 was also reported in older age groups in some countries. The sensitivity of macrocytosis in detecting Vitamin B12 deficiency was only 4.6%. CONCLUSION: Vitamin B12 deficiency is an important population health issue in newly-arrived refugees from many countries. All newly-arrived refugees should be tested for Vitamin B12 deficiency. Ongoing research should investigate causes, treatment, and ways to mitigate food insecurity, and the contribution of such measures to enhancing the health of the refugee communities.

  15. Imerslund-Grasbeck syndrome in a Chinese family with distinct skin lesions refractory to vitamin B12.

    OpenAIRE

    Lin, S H; Sourial, N A; Lu, K C; Hsueh, E J

    1994-01-01

    Two brothers in a Chinese family with selective malabsorption of vitamin B12 associated with proteinuria (Imerslund-Grasbeck syndrome) presented with widespread mottled skin pigmentation, termed poikiloderma. In contrast to anaemia, this pigmentary disturbance remained unresponsive to vitamin B12 replacement. This is different from the reported hyperpigmentation sometimes seen in vitamin B12 deficiency which is reversible following treatment. As far as is known, an irreversible and persistent...

  16. A combined supplementation of vitamin B12 and omega-3 fatty acids across two generations improves cardiometabolic variables in rats.

    Science.gov (United States)

    Khaire, Amrita; Rathod, Richa; Randhir, Karuna; Kale, Anvita; Joshi, Sadhana

    2016-09-14

    Our earlier studies indicate that micronutrients (vitamin B12, folic acid) and omega-3 fatty acids especially docosahexaenoic acid (DHA) are interlinked in one carbon cycle. The present study examines the effects of a sustained vitamin B12 deficiency/supplementation in the presence of omega-3 fatty acids across two generations on the pregnancy outcome and cardiometabolic profile [blood pressure, plasma lipid profile (cholesterol and triglycerides), plasma/liver fatty acid profile and hepatic lipid metabolism] in the second generation adult Wistar rat offspring. Two generations of animals were fed the following diets: control; vitamin B12 deficient; vitamin B12 supplemented; vitamin B12 deficient diet supplemented with omega-3 fatty acids; vitamin B12 and omega-3 fatty acid supplemented diets. Male offspring were sacrificed at 3 months of age. Vitamin B12 deficiency lowered the weight gain (p blood pressure, and lowered the levels of plasma/liver DHA (p lipid profile. Vitamin B12 supplementation showed weight gain, blood pressure and the fatty acid profile similar to the control. However, it increased (p acid supplementation to the vitamin B12 deficient group lowered the weight gain although the levels of cardiometabolic variables were comparable to the control. Omega-3 fatty acid supplementation in the presence of vitamin B12 improved the pregnancy outcome and all cardio-metabolic variables. Our study highlights the adverse effects of sustained vitamin B12 deficiency across two generations on the pregnancy outcome, fatty acid profile and blood pressure while a combined supplementation of vitamin B12 and omega-3 fatty acids is beneficial.

  17. Techno-functional differentiation of two vitamin B12 producing Lactobacillus plantarum strains: an elucidation for diverse future use.

    Science.gov (United States)

    Bhushan, Bharat; Tomar, S K; Chauhan, Arun

    2017-01-01

    An appropriate selection of Lactobacillus strain (probiotic/starter/functional) on the basis of its techno-functional characteristics is required before developing a novel fermented functional food. We compared vitamin B 12 (B 12 , cobalamin) producing Lactobacillus plantarum isolates, BHM10 and BCF20, for functional (vitamin over-production, genomic insight to B 12 structural genes, and probiotic attributes) and technological [milks (skim and soy) fermentation and B 12 bio-fortification] characteristics. Addition of B 12 precursors (5-amonolevulinate and dimethylbenzimidazole) to cobalamin-free fermentation medium increased vitamin production in BHM10, BCF20, and DSM20016 (a positive standard) by 3.4-, 4.4-, and 3.86-folds, respectively. Three important B 12 structural genes were detected in L. plantarum species (strains BHM10 and BCF20) by PCR for the first time. The gene sequences were submitted to NCBI GenBank and found phylogenetically closer to respective sequences in B 12 producing Lactobacillus reuteri strains. During comparative probiotic testing, BCF20 showed significantly higher (p < 0.05 to p < 0.001) gastrointestinal tolerance and cell surface hydrophobicity (p < 0.05) than BHM10. Moreover, only BCF20 was found positive for BSH activity and also exhibited comparatively better antagonistic potential against potent pathogens. Conversely, high acid and bile susceptible strain BHM10 displayed significantly higher soy milk fermentation and resultant B 12 bio-fortification abilities during technological testing. Two B 12 quantification techniques, UFLC and competitive immunoassay, confirmed the in vitro and in situ bio-production of bio-available form of B 12 after BHM10 fermentation. Conclusively, techno-functional differentiation of two B 12 producing strains elucidates their diverse future use; BCF20 either for B 12 over-production (in vitro) or as a probiotic candidate, while BHM10 for cobalamin bio-fortification (in situ) in soy milk.

  18. Stability and aromaticity of nH2@B12N12 (n=1–12 clusters

    Directory of Open Access Journals (Sweden)

    Pratim K. Chattaraj

    2011-04-01

    Full Text Available Standard ab initio and density functional calculations are carried out to determine the structure, stability, and reactivity of B12N12 clusters with hydrogen doping. To lend additional support, conceptual DFT-based reactivity descriptors and the associated electronic structure principles are also used. Related cage aromaticity of this B12N12 and nH2@B12N12 are analyzed through the nucleus independent chemical shift values.

  19. Chemoradiotherapy of cancer using boronated monoclonal antibodies. Progress report, December 1, 1982-November 30, 1983

    International Nuclear Information System (INIS)

    Soloway, A.H.

    1984-01-01

    The feasibility was established of using antibodies for the delivery of 10 B. Problems faced included 1) preservation of antibody activity following boronation, 2) antigenic receptor site density of the target cells, and 3) delivery of a critical number of 10 B atoms per cell. The linkage of a heavily boronated polymeric species to antibody by means of a single functional group allow for the delivery of a large number 10 B atoms per antibody molecule without a significant reduction in affinity. Both the polyclonally derived anti-thymocyte globulin (ATG) and the monoclonal anti-colorectal carcinoma antibody (17-1A) recognize antigens that are expressed with a density of approximately 10 6 epitopes per cell. The major concept that we advance is that just as effective cancer chemotherapy is based on the use of a combination of drugs, similarly a combination of compounds could be employed to deliver the requisite amount of 10 B to tumor target cells. This could include compounds such as Na 2 B 12 H 11 Sh together with boronated antibodies directed against tumor associated antigens. (DT)

  20. Homocysteine, vitamin B12 and folate levels in premature coronary artery disease

    Directory of Open Access Journals (Sweden)

    Fallah Nader

    2006-09-01

    Full Text Available Abstract Background Hyperhomocysteinemia is known as an independent risk factor of atherosclerosis, but the probable role of hyperhomocysteinemia in premature Coronary Artery Disease (CAD is not well studied. The aim of this study was to assess the role of hyperhomocysteinemia, folate and Vitamin B12 deficiency in the development of premature CAD. Methods We performed an analytical case-control study on 294 individuals under 45 years (225 males and 69 females who were admitted for selective coronary angiography to two centers in Tehran. Results After considering the exclusion criteria, a total number of 225 individuals were enrolled of which 43.1% had CAD. The mean age of participants was 39.9 +/- 4.3 years (40.1 +/- 4.2 years in males and 39.4 +/- 4.8 years in females. Compared to the control group, the level of homocysteine measured in the plasma of the male participants was significantly high (14.9 +/- 1.2 versus 20.3 +/- 1.9 micromol/lit, P = 0.01. However there was no significant difference in homocysteine level of females with and without CAD (11.8 +/- 1.3 versus 11.5 ± 1.1 micromol/lit, P = 0.87. Mean plasma level of folic acid and vitamin B12 in the study group were 6.3 +/- 0.2 and 282.5 +/- 9.1 respectively. Based on these findings, 10.7% of the study group had folate deficiency while 26.6% had Vitamin B12 deficiency. Logistic regression analysis for evaluating independent CAD risk factors showed hyperhomocysteinemia as an independent risk factor for premature CAD in males (OR = 2.54 0.95% CI 1.23 to 5.22, P = 0.01. Study for the underlying causes of hyperhomocysteinemia showed that male gender and Vitamin B12 deficiency had significant influence on incidence of hyperhomocysteinemia. Conclusion We may conclude that hyperhomocysteinemia is an independent risk factor for CAD in young patients (bellow 45 years old – especially in men -and vitamin B12 deficiency is a preventable cause of hyperhomocysteinemia.

  1. EVALUATION OF SERUM VITAMIN B12 LEVELS IN TYPE 2 DIABETES PATIENTS ON METFORMIN THERAPY ATTENDING A TERTIARY CARE HOSPITAL

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    Anand Kalakappa Koppad

    2017-11-01

    Full Text Available BACKGROUND Type 2 Diabetes Mellitus (T2DM is an endocrine disorder and a heterogeneous group of syndromes characterised by an elevation of fasting blood glucose that is caused by a relative or absolute deficiency in insulin. Serum vitamin B12 levels have been reported to be inversely associated with the dose and duration of metformin use. Vitamin B12 deficiency is a treatable condition. However, there is insufficient data regarding prevalence of vitamin B12 deficiency in the South Indian population. Hence, the study was undertaken to evaluate serum vitamin B12 levels in T2DM on metformin therapy. MATERIALS AND METHODS A total of 100 T2DM patients attending Outpatient Department (OPD or admitted under Department of General Medicine of KIMS, Hubli, during the time period of 2 years were taken for study considering the inclusion and exclusion criteria. Qualifying patients underwent detailed history, clinical examination, routine investigation and vitamin B12 estimation. RESULTS Majority were in the age group of 45-59 years making 42% of the total. The age group in most patients having vitamin B12 deficiency was >60 years. Males had more vitamin B12 deficiency forming 54.5%. Vitamin B12 deficiency was more in hypertensive group accounting for 71.4%, which was statistically significant. Most of the vitamin B12 deficiency patients had diabetes duration >10 years. Most of the vitamin B12 deficient patients were taking metformin therapy for longer years (≥10 years and in higher dose (>2 g/day. Most of the vitamin B12 deficient diabetes patients were overweight forming 52.5% of the total. CONCLUSION Longer duration of diabetes increases the risk of developing vitamin B12 deficiency on metformin therapy. The higher dose of metformin intake had inverse relation with vitamin B12 levels. Longer duration of metformin intake causes vitamin B12 deficiency and hence should be screened for vitamin B12 deficiency and can be supplemented with vitamin B12.

  2. Association of Helicobacter pylori infection with serum vitamin B12 level in women of gestational age in Khorram Abad

    Directory of Open Access Journals (Sweden)

    fatemeh Yari

    2006-02-01

    Findings: There was no significant difference between mean age of HP positive and HP negative participants. 76 out of 110 (72.2% samples were HP positive. The rate of HP seropositivity was significantly higher in patients with serum vitamin B12 level less than 12 pg/ml. who had lower and moderate vitamin B12 levels (145-180 pg/ml, that is 94% vs 64.5%, P<0.013. Conclusion: High HP seropositivity rate among patients with low-normal less serum vitamin B12 levels than normal indicates that there may be an association between HP infection and serum vitamin B12 levels.

  3. Short communication: Factors affecting vitamin B12 concentration in milk of commercial dairy herds: An exploratory study.

    Science.gov (United States)

    Duplessis, M; Pellerin, D; Cue, R I; Girard, C L

    2016-06-01

    Only bacteria can synthesize vitamin B12, and this requires adequate Co supply. The natural source of vitamin B12 in human diets comes from animal products, especially those from ruminants. This study aimed to describe variability regarding vitamin B12 concentration in milk among and within commercial dairy herds in early lactation. A secondary objective was to explore potential causes for this variability such as genetic variation and diet characteristics. In total, 399 dairy cows (135 primiparous and 264 multiparous; 386 Holstein and 13 Jersey cows) in 15 commercial herds were involved. Milk samples were taken at 27.4±4.1 and 55.4±4.1d in milk. Neither parity (primiparous vs. multiparous) nor sampling time affected milk concentrations of vitamin B12. Nevertheless, vitamin B12 concentration in milk was highly variable among and within dairy herds. The lowest vitamin B12 concentration in milk of cows was observed in the Jersey herd. Among herds, vitamin B12 concentration in milk ranged from 2,309 to 3,878 pg/mL; one glass (250mL) of milk from those herds would provide between 23 and 40% of the vitamin B12 recommended daily allowance. Among individual cows, however, this provision varied between 16 and 57% of the recommendation. In spite of the limited size of the studied population, the heritability value was 0.23, suggesting that genetic selection could modify milk vitamin B12 concentration. We observed a positive relationship between milk vitamin B12 concentration and dietary acid detergent fiber content and a negative relationship between milk concentration of vitamin B12 and dietary crude protein content. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  4. HSD17B12 gene rs11037575 C>T polymorphism confers neuroblastoma susceptibility in a Southern Chinese population

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    Zhang ZR

    2017-04-01

    Full Text Available Zhuorong Zhang,1,2 Yan Zou,2 Jinhong Zhu,3 Ruizhong Zhang,2 Tianyou Yang,2 Fenghua Wang,2 Huimin Xia,1,2 Jing He,2 Zhichun Feng1,4–6 1Southern Medical University, Guangzhou, Guangdong, 2Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 3Molecular Epidemiology Laboratory, Department of Laboratory Medicine, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 4Division of Neonatology, Affiliated BaYi Children’s Hospital, Clinical Medical College in PLA Army General Hospital, Southern Medical University, 5National Engineering Laboratory for Birth Defects Prevention and Control of Key Technology, 6Beijing Key Laboratory of Pediatric Organ Failure, Beijing, People’s Republic of China Abstract: A previous genome-wide association study (GWAS identified four genetic polymorphisms (rs1027702 near DUSP12, rs10055201 in IL31RA, rs2619046 in DDX4, and rs11037575 in HSD17B12 gene that were associated with neuroblastoma susceptibility, especially for low-risk subjects. The aim of this study was to examine the association between these four polymorphisms and neuroblastoma susceptibility in a Southern Chinese population composed of 256 cases and 531 controls. Overall, among all the polymorphisms, single-locus analysis only revealed significant association between the HSD17B12 rs11037575 C>T polymorphism and neuroblastoma susceptibility (CT vs CC: adjusted odds ratio [OR] =0.71, 95% confidence interval [CI] =0.51–0.97, P=0.030. Moreover, stratified analysis indicated that the rs11037575 T allele was associated with decreased neuroblastoma risk among the children aged 0–18 months (adjusted OR =0.60, 95% CI =0.37–0.97, P=0.036; regarding the tumor site, this polymorphism protected against tumor in the mediastinum (adjusted OR =0.59, 95% CI =0.37–0.94, P=0.025. When risk genotypes were combined, we found that girls with

  5. Targeting the active site of the placental isozyme of alkaline phosphatase by phage-displayed scFv antibodies selected by a specific uncompetitive inhibitor

    Directory of Open Access Journals (Sweden)

    Kala Mrinalini

    2005-12-01

    . Conclusion The results demonstrate the biochemical modulation of scFv binding. Also, the scFvs bound to the active site and denied the access to the substrate. The selection strategy could generate specific anti-enzyme antibodies to PLAP that can potentially be used for targeting, for modulating enzyme activity in in vitro and in vivo and as probes for the active site. This strategy also has a general application in selecting antibodies from combinatorial libraries to closely related molecules and conformations.

  6. Vitamin B12 in metformin-treated diabetic patients: a cross-sectional study in Brazil Vitamina B12 em pacientes diabéticos usando metformina: um corte transversal no Brasil

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    Monique Nervo

    2011-02-01

    Full Text Available OBJECTIVE: The objective of this study was to evaluate the presence of vitamin B12 deficiency and the factors associated with serum vitamin B12 levels in a sample of metformin-treated Brazilian diabetic patients. METHOD: Cross-sectional study. RESULTS: 144 patients were included. Serum vitamin B12 levels were low (OBJETIVO: O objetivo deste estudo foi avaliar a prevalência de deficiência de vitamina B12 em pacientes diabéticos brasileiros tratados com metformina e os fatores associados aos níveis séricos de vitamina B12. MÉTODO: Corte transversal. RESULTADOS: 144 pacientes foram incluídos. Os níveis séricos de vitamina B12 foram baixos (< 125 pmol/L em 10 pacientes (6,9% e possivelmente baixos (125 - 250pmol/L em 53 pacientes (36,8%. Os níveis séricos de vitamina B12 foram associados negativamente à idade (B = -3,17; β = -0,171; p = 0,037 e à duração do uso de metformina (B = -33,36; β= -0,161; p = 0,048 e positivamente com a ingestão estimada de vitamina B12 (B = 67,96; β = 0,249; p = 0,002. CONCLUSÃO: Estes resultados sugerem alta prevalência de deficiência de vitamina B12 em pacientes diabéticos tratados com metformina. Pacientes mais velhos, em uso de metformina há muito tempo e com ingestão baixa de vitamina B12 estão provavelmente mais predispostos a essa deficiência.

  7. TD-DFT Insight into Photodissociation of Co-C Bond in Coenzyme B12

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    Pawel Michal Kozlowski

    2014-02-01

    Full Text Available Coenzyme B12 (AdoCbl is one of the most biologically active forms of vitamin B12, and continues to be a topic of active research interest. The mechanism of Co-C bond cleavage in AdoCbl, and the corresponding enzymatic reactions are however, not well understood at the molecular level. In this work, time-dependent density functional theory (TD-DFT has been applied to investigate the photodissociation of coenzyme B12. To reduce computational cost, while retaining the major spectroscopic features of AdoCbl, a truncated model based on ribosylcobalamin (RibCbl was used to simulate Co-C photodissociation. Equilibrium geometries of RibCbl were obtained by optimization at the DFT/BP86/TZVP level of theory, and low-lying excited states were calculated by TD-DFT using the same functional and basis set. The calculated singlet states, and absorption spectra were simulated in both the gas phase, and water, using the polarizable continuum model (PCM. Both spectra were in reasonable agreement with experimental data, and potential energy curves based on vertical excitations were plotted to explore the nature of Co-C bond dissociation. It was found that a repulsive 3(σCo-C → σ*Co-C triplet state became dissociative at large Co-C bond distance, similar to a previous observation for methylcobalamin (MeCbl. Furthermore, potential energy surfaces (PESs obtained as a function of both Co-CRib and Co-NIm distances, identify the S1 state as a key intermediate generated during photoexcitation of RibCbl, attributed to a mixture of a MLCT (metal-to-ligand charge transfer and a σ bonding-ligand charge transfer (SBLCT states.

  8. Importance of Neutralizing Monoclonal Antibodies Targeting Multiple Antigenic Sites on the Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein To Avoid Neutralization Escape

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lingshu; Shi, Wei; Chappell, James D.; Joyce, M. Gordon; Zhang, Yi; Kanekiyo, Masaru; Becker, Michelle M.; van Doremalen, Neeltje; Fischer, Robert; Wang, Nianshuang; Corbett, Kizzmekia S.; Choe, Misook; Mason, Rosemarie D.; Van Galen, Joseph G.; Zhou, Tongqing; Saunders, Kevin O.; Tatti, Kathleen M.; Haynes, Lia M.; Kwong, Peter D.; Modjarrad, Kayvon; Kong, Wing-Pui; McLellan, Jason S.; Denison, Mark R.; Munster, Vincent J.; Mascola, John R.; Graham, Barney S.; Gallagher, Tom

    2018-03-07

    ABSTRACT

    Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with ~35% mortality. The potential for a future pandemic originating from animal reservoirs or health care-associated events is a major public health concern. There are no vaccines or therapeutic agents currently available for MERS-CoV. Using a probe-based single B cell cloning strategy, we have identified and characterized multiple neutralizing monoclonal antibodies (MAbs) specifically binding to the receptor-binding domain (RBD) or S1 (non-RBD) regions from a convalescent MERS-CoV-infected patient and from immunized rhesus macaques. RBD-specific MAbs tended to have greater neutralizing potency than non-RBD S1-specific MAbs. Six RBD-specific and five S1-specific MAbs could be sorted into four RBD and three non-RBD distinct binding patterns, based on competition assays, mapping neutralization escape variants, and structural analysis. We determined cocrystal structures for two MAbs targeting the RBD from different angles and show they can bind the RBD only in the “out” position. We then showed that selected RBD-specific, non-RBD S1-specific, and S2-specific MAbs given prophylactically prevented MERS-CoV replication in lungs and protected mice from lethal challenge. Importantly, combining RBD- and non-RBD MAbs delayed the emergence of escape mutations in a cell-based virus escape assay. These studies identify MAbs targeting different antigenic sites on S that will be useful for defining mechanisms of MERS-CoV neutralization and for developing more effective interventions to prevent or treat MERS-CoV infections.

    IMPORTANCEMERS-CoV causes a highly lethal respiratory infection for which no vaccines or antiviral therapeutic options are currently available. Based on continuing exposure from established reservoirs in dromedary camels and bats, transmission of MERS-CoV into humans and future outbreaks are expected. Using

  9. Acquired thermotolerance and heat shock in the extremely thermophilic archaebacterium Sulfolobus sp. strain B12.

    OpenAIRE

    Trent, J D; Osipiuk, J; Pinkau, T

    1990-01-01

    The extreme thermophile Sulfolobus sp. strain B12 exhibits an acquired thermotolerance response. Thus, survival of cells from a 70 degrees C culture at the lethal temperature of 92 degrees C was enhanced by as much as 6 orders of magnitude over a 2-h period if the culture was preheated to 88 degrees C for 60 min or longer before being exposed to the lethal temperature. In eubacteria and eucaryotes, acquired thermotolerance correlates with the induced synthesis of a dozen or so proteins known ...

  10. Measurement of total-body cobalt-57 vitamin B12 absorption with a gamma camera

    International Nuclear Information System (INIS)

    Cardarelli, J.A.; Slingerland, D.W.; Burrows, B.A.; Miller, A.

    1985-01-01

    Previously described techniques for the measurement of the absorption of [ 57 Co]vitamin B 12 by total-body counting have required an iron room equipped with scanning or multiple detectors. The present study uses simplifying modifications which make the technique more available and include the use of static geometry, the measurement of body thickness to correct for attenuation, a simple formula to convert the capsule-in-air count to a 100% absorption count, and finally the use of an adequately shielded gamma camera obviating the need of an iron room

  11. A review of radioisotope techniques in the study of vitamin B12 absorption

    International Nuclear Information System (INIS)

    Boddy, K.

    1976-01-01

    The five in vivo tests in common use for the study of vitamin B 12 absorption, namely, 1) faecal excretion method, 2) urinary excretion method, 3) plasma radioactivity method, 4) hepatic uptake method, and 5) whole-body counting method, are described. The merits, disadvantages and limitations of each method are considered in a clinical context. Whole-body counting is regarded as the method of choice where appropriate facilities are available and when the delay of about 7 days in obtaining the result is acceptable. The plasma radioactivity method can provide concurrently a rapid assessment. (author)

  12. Ultrasonographic evaluation to diagnose hepatic lipidosis in Egyptian Zaraibi goats with vitamin B12 deficiency

    OpenAIRE

    Sabry A. El-Khodery; Hussein S. Hussein; Mohamed E. El-Boshy; Medhat N. Nassif

    2011-01-01

    As little is known about the ultrasonographic features of hepatic lipidosis (white liver disease) in goats, this study was undertaken to evaluate the use of ultrasound for the diagnosis of hepatic lipidosis associated with vitamin B12 (cyanocobalamin) deficiency in Egyptian Zaraibi goats. A total of 38 goats (28 with weight loss, diarrhoea and anaemia and 10 clinically healthy) were studied. Twenty-one goats were demonstrated to have cobalt and cyanocobalamin deficiency (0.33 ± 0.12 μmol/l an...

  13. Blood homocysteine, folic acid, vitamin B12 and vitamin B6 levels in psoriasis patients

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    Meltem Uslu

    2017-09-01

    Full Text Available Background and Design: Homocysteine, a sulfur-containing amino acid, is known to be related with autoimmunity-inflammation, cardiovascular disease and DNA methylation. In this case-control study, we aimed to determine plasma homocysteine, folic acid, vitamin B12 and vitamin B6 levels in patients with psoriasis. Materials and Methods: Smoking, alcohol and coffee consumption habits were recorded in adult patients with plaque-type psoriasis and age- and sex-matched controls. Height and weight measurements were performed and Psoriasis Area and Severity Index (PASI scores were calculated. Fasting venous blood samples were collected to determine homocysteine, folic acid, vitamin B12, vitamin B6, glucose, total cholesterol, triglyceride, high density lipoprotein (HDL, erythrocyte sedimentation rate (ESR, and C-reactive protein (CRP levels. Results: There was no significant difference between psoriasis patients (n=43 and controls (n=47 in body mass index and alcohol and coffee consumption. Smoking rate was significantly high in psoriasis patients. The median PASI score was 10.0 (8.3-12.8. Plasma homocysteine, folic acid, vitamin B12, vitamin B6, total cholesterol, triglyseride, ESR and CRP values were not significantly different between patients and the controls. HDL level was low in psoriasis patients (p=0.001. Plasma homocysteine level was higher in males than in females. There was no relationship of homocysteine levels with patient’s age, PASI scores, ESR, CRP values and lipids. Homocysteine levels were inversely related with folic acid and vitamin B12 (p=0.000, r=-0.436, p=0.047, r=-0.204, respectively. We did not find any relationship between homocysteine and vitamin B6 levels. Conclusion: There was no increase in plasma homocysteine levels in psoriasis patients we followed up. Homocysteine level increases in inflammatory disorders and this increase is accepted as a cardiovascular disease marker. Homocysteine homeostasis may be balanced in our

  14. Expeditious Synthesis of Noble Metal Nanoparticles Using Vitamin B12 under Microwave Irradiation

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    Changseok Han

    2015-08-01

    Full Text Available A greener synthesis protocol for noble nanometals is developed using vitamin B12 as a reducing and capping agent in conjunction with the use of microwaves. Successful assembly of nanoparticles or microparticles with varied shapes and sizes have been demonstrated. The synthesized Ag, Au, and Pd samples were thoroughly characterized with X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high resolution transmission microscopy, and UV-visible spectrophotometry, confirming that metallic Ag, Au, and Pd were synthesized by the green chemistry method.

  15. Rapid microbiological assay of serum vitamin B 12 by electronic counter.

    Science.gov (United States)

    Stuart, J; Sklaroff, S A

    1966-01-01

    A new method of measuring the growth of Lactobacillus leichmannii is reported. Its adoption for the estimation of serum vitamin B(12) levels shortens the incubation period required to five hours at 45 degrees C. The method is compared statistically with a standard method of estimation, requiring incubation at 37 degrees C., by duplicate determinations on 106 hospital patients. The significance of the apparently decreased accuracy of the new method at low serum levels is discussed, and a re-appraisal of the optimum growth temperature of Lactobacillus leichmannii suggested.

  16. High-level folate production in fermented foods by the B12 producer Lactobacillus reuteri JCM1112

    NARCIS (Netherlands)

    Santos, F.; Wegkamp, A.; de Vos, W.M.; Smid, E.J.; Hugenholtz, J.

    2008-01-01

    We observed that Lactobacillus reuteri JCM1112 produces B12 and folate. However, the folate/B12 mass ratio found was far below that desired for human consumption (~170:1). We used metabolic engineering applying genetic and physiological approaches to improve this ratio and developed a generic and

  17. Optimization of folic acid, vitamin B-12, and vitamin B-6 supplements in pediatric patients with sickle cell disease

    NARCIS (Netherlands)

    van der Dijs, Fey P L; Fokkema, M Rebecca; Dijck-Brouwer, D A Janneke; Niessink, Bram; van der Wal, Thaliet I C; Schnog, John-John B; Duits, Ashley J; Muskiet, Fred D; Muskiet, Frits A J

    Using homocysteine as a functional marker, we determined optimal folic acid, vitamin B-12, and vitamin B-6 dosages in 21 pediatric sickle cell disease (SCD) patients (11 HbSS, 10 HbSC; 7-16 years). Daily supplements of folic acid (400, 700, or 1,000 mug), vitamin B-12 (1, 3, or 5 U.S. 1989 RDA), and

  18. Effect of vitamin B12 pulse addition on the performance of cobalt deprived anaerobic granular sludge bioreactors

    KAUST Repository

    Fermoso, Fernando G.; Bartacek, Jan; Lens, Piet N.L.

    2010-01-01

    The effect of a pulse addition of vitamin B12 as cobalt source to restore the performance of cobalt depleted methanol-fed bioreactors was investigated. One upflow anaerobic sludge bed (UASB) reactor was supplied with a pulse of vitamin B12, and its

  19. Human Vitamin B12 Absorption and Metabolism are Measured by Accelerator Mass Spectrometry Using Specifically Labeled 14C-Cobalamin

    International Nuclear Information System (INIS)

    Carkeet, C; Dueker, S R; Lango, J; Buchholz, B A; Miller, J W; Green, R; Hammock, B D; Roth, J R; Anderson, P J

    2006-01-01

    There is need for an improved test of human ability to assimilate dietary vitamin B 12 . Assaying and understanding absorption and uptake of B 12 is important because defects can lead to hematological and neurological complications. Accelerator mass spectrometry (AMS) is uniquely suited for assessing absorption and kinetics of 14 C-labeled substances after oral ingestion because it is more sensitive than decay counting and can measure levels of carbon-14 ( 14 C) in microliter volumes of biological samples, with negligible exposure of subjects to radioactivity. The test we describe employs amounts of B 12 in the range of normal dietary intake. The B 12 used was quantitatively labeled with 14 C at one particular atom of the DMB moiety by exploiting idiosyncrasies of Salmonellametabolism. In order to grow aerobically on ethanolamine, S. entericamust be provided with either pre-formed B 12 or two of its precursors: cobinamide and dimethylbenzimidazole (DMB). When provided with 14 C-DMB specifically labeled in the C2 position, cells produced 14 C-B 12 of high specific activity (2.1 GBq/mmol, 58 mCi/mmol) and no detectable dilution of label from endogenous DMB synthesis. In a human kinetic study, a physiological dose (1.5 mg, 2.2 KBq/59 nCi) of purified 14 C-B 12 was administered and showed plasma appearance and clearance curves consistent with the predicted behavior of the pure vitamin. This method opens new avenues for study of B 12 assimilation

  20. Vitamin B-12 deficiency and the lack of its consequences in type 2 diabetes patients using metformin

    NARCIS (Netherlands)

    de Groot-Kamphuis, D. M.; van Dijk, P. R.; Groenier, K. H.; Houweling, Sebastiaan; Bilo, H. J. G.; Kleefstra, N.

    Objectives: To study vitamin B-12 concentrations in patients with type 2 diabetes with and without metformin use and to identify risk factors and consequences of low vitamin B-12 concentrations. Research design and methods: This study had a cross-sectional design. During eight weeks all patients

  1. Vitamin B12 deficiency and the lack of its consequences in type 2 diabetes patients using metformin

    NARCIS (Netherlands)

    de Groot-Kamphuis, D M; van Dijk, P R; Groenier, K H; Houweling, S T; Bilo, H J G; Kleefstra, N

    OBJECTIVES: To study vitamin B12 concentrations in patients with type 2 diabetes with and without metformin use and to identify risk factors and consequences of low vitamin B12 concentrations. RESEARCH DESIGN AND METHODS: This study had a cross-sectional design. During eight weeks all patients with

  2. Associations of genetic determinants of serum vitamin B12 and folate concentrations with hay fever and asthma

    DEFF Research Database (Denmark)

    Skaaby, Tea; Taylor, Amy E; Jacobsen, Rikke K

    2017-01-01

    Background/objectives: Studies of the effect of vitamin B12 and folate on the risk of asthma and hay fever have shown inconsistent results that may be biased by reverse causation and confounding. We used a Mendelian randomization approach to examine a potential causal effect of vitamin B12 and fo...

  3. Vitamin B-12 Concentrations in Breast Milk Are Low and Are Not Associated with Reported Household Hunger, Recent Animal-Source Food, or Vitamin B-12 Intake in Women in Rural Kenya.

    Science.gov (United States)

    Williams, Anne M; Chantry, Caroline J; Young, Sera L; Achando, Beryl S; Allen, Lindsay H; Arnold, Benjamin F; Colford, John M; Dentz, Holly N; Hampel, Daniela; Kiprotich, Marion C; Lin, Audrie; Null, Clair A; Nyambane, Geoffrey M; Shahab-Ferdows, Setti; Stewart, Christine P

    2016-05-01

    Breast milk vitamin B-12 concentration may be inadequate in regions in which animal-source food consumption is low or infrequent. Vitamin B-12 deficiency causes megaloblastic anemia and impairs growth and development in children. We measured vitamin B-12 in breast milk and examined its associations with household hunger, recent animal-source food consumption, and vitamin B-12 intake. In a cross-sectional substudy nested within a cluster-randomized trial assessing water, sanitation, hygiene, and nutrition interventions in Kenya, we sampled 286 women 1-6 mo postpartum. Mothers hand-expressed breast milk 1 min into a feeding after 90 min observed nonbreastfeeding. The Household Hunger Scale was used to measure hunger, food intake in the previous week was measured with the use of a food-frequency questionnaire (FFQ), and vitamin B-12 intake was estimated by using 24-h dietary recall. An animal-source food score was based on 10 items from the FFQ (range: 0-70). Breast milk vitamin B-12 concentration was measured with the use of a solid-phase competitive chemiluminescent enzyme immunoassay and was modeled with linear regression. Generalized estimating equations were used to account for correlated observations at the cluster level. Median (IQR) vitamin B-12 intake was 1.5 μg/d (0.3, 9.7 μg/d), and 60% of women consumed hunger prevalence was 27%; the animal-source food score ranged from 0 to 30 item-d/wk. Hunger and recent animal-source food and vitamin B-12 intake were not associated with breast milk vitamin B-12 concentrations. Maternal age was negatively associated with breast milk vitamin B-12 concentrations. Most lactating Kenyan women consumed less than the estimated average requirement of vitamin B-12 and had low breast milk vitamin B-12 concentrations. We recommend interventions that improve vitamin B-12 intake in lactating Kenyan women to foster maternal health and child development. The main trial was registered at clinicaltrials.gov as NCT01704105. © 2016

  4. Investigations with a simplified method for radiometric determination of vitamin B12 in body fluids and feeding stuffs

    International Nuclear Information System (INIS)

    Menke, K.H.; Kohlberger, G.; Koenemund, A.

    1979-01-01

    A modified method for radiometrical determination of vitamin B 12 is described, which in difference to the known methods is based on measurement of free B 12 after absorption to albumin-coated charcoal instead of measurement of intrinsic factor B 12 -complex. The conditions for extraction from serum, milk, rumen-liquor and urine have been investigated and the effect of pH on IF-B 12 -binding in presence of these body fluids examined. Parallel microbiological determinations (O.m.- and L.1.-test) were in good correlation (r = 0,93-0,97) to radiometrically determined B 12 -contents in milk and rumen-liquor, but not to that in serum of dairy cows (r = 0,54-0,82). The analytical procedures are given in detail. (orig.) [de

  5. Probing Reversible Chemistry in Coenzyme B12-Dependent Ethanolamine Ammonia Lyase with Kinetic Isotope Effects

    Science.gov (United States)

    Jones, Alex R; Rentergent, Julius; Scrutton, Nigel S; Hay, Sam

    2015-01-01

    Coenzyme B12-dependent enzymes such as ethanolamine ammonia lyase have remarkable catalytic power and some unique properties that enable detailed analysis of the reaction chemistry and associated dynamics. By selectively deuterating the substrate (ethanolamine) and/or the β-carbon of the 5′-deoxyadenosyl moiety of the intrinsic coenzyme B12, it was possible to experimentally probe both the forward and reverse hydrogen atom transfers between the 5′-deoxyadenosyl radical and substrate during single-turnover stopped-flow measurements. These data are interpreted within the context of a kinetic model where the 5′-deoxyadenosyl radical intermediate may be quasi-stable and rearrangement of the substrate radical is essentially irreversible. Global fitting of these data allows estimation of the intrinsic rate constants associated with CoC homolysis and initial H-abstraction steps. In contrast to previous stopped-flow studies, the apparent kinetic isotope effects are found to be relatively small. PMID:25950663

  6. Fast and effective transformation of toxaphene by superreduced vitamin B12 and dicyanocobalamin

    Energy Technology Data Exchange (ETDEWEB)

    Recke, R. von der; Gaul, S. [Inst. of Food Chemistry, Univ. of Hohenheim, Stuttgart (Germany); Ruppe, S.; Vetter, W. [Inst. of Food and Nutrition, Friedrich-Schiller-Univ. Jena (Germany); Neumann, A. [Dept. of Technical Biology, Univ. of Karlsruhe (Germany)

    2004-09-15

    The chloropesticide toxaphene (Camphechlor, Melipax) has been used in high quantities since 1945. Toxaphene has been classified as a persistent organohalogen pollutant (POP) and belongs to the ''dirty dozen''. Due to its heavy use in the 1960s and 1970s, several environmental compartments were significantly contaminated with toxaphene. For instance, concentrations in polluted areas could exceed 1 mg/kg sediment. Recently, it was shown that cultures of the isolated bacterium Dehalospirillum multivorans transformed toxaphene in a similar way as anaerobic sediment and soil samples. The potential of D. multivorans for the anaerobic transformation of organohalogens was previously demonstrated for chloroethenes (PCE and TCE) 6. The reactive dehalogenase of D. multivorans contains a corrinoide co-factor. In this study two corrinoids cyanocobalamin (vitamin B12, CCA) and dicyanocobinamide (DCC) were used in their superreduced forms (i. e. those having the central atom Co in the oxidation state +I). Interestingly, a very fast transformation of toxaphene was observed with superreduced DCC. Unfortunately, the transformation occurred so fast that no transformation products could be identified. For this reason, we performed further experiments with the less reactive superreduced vitamin B12 (CCA{sub s}). CCA{sub s} has previously been used for the transformation of PCBs, hexachlorobenzene, chloroform, and chloroethanes.

  7. Physiological role of vitamin B12 in a methanol-utilizing bacterium, Protaminobacter ruber

    International Nuclear Information System (INIS)

    Shimizu, S.; Ueda, S.; Sato, K.

    1984-01-01

    The methanol-utilizing bacterium Protaminobacter ruber is able to produce a relatively large amount of vitamin B 12 . The present study aims at the physiological role of vitamin B 12 in P. ruber. P. ruber was found to contain the two sequential reactions of glutamate mutase with β-methylaspartase and propionyl-CoA carboxylase with methylmalonyl-CoA mutase. Considering the presence of these enzyme systems and the reaction from mesaconyl-CoA to glyoxylate and propionyl-CoA, it could be considered that the formation of glutamate from α-ketoglutarate, the conversion of glutamate to mesaconate via β-methylaspartate, the activation of mesaconate with CoA to form mesaconyl-CoA, the cleavage of mesaconyl-CoA to glyoxylate and propionyl-CoA, the carboxylation of propionyl-CoA to methylmalonyl-CoA, and the isomerization of methylmalonyl-CoA to succinyl-CoA require cobalamine as a cofactor. 29 refs., 2 figs., 2 tabs

  8. Supplementing lactating dairy cows with a vitamin B12 precursor, 5,6-dimethylbenzimidazole, increases the apparent ruminal synthesis of vitamin B12.

    Science.gov (United States)

    Brito, A; Chiquette, J; Stabler, S P; Allen, R H; Girard, C L

    2015-01-01

    Cobalamin (CBL), the biologically active form of vitamin B12, and its analogs, are produced by bacteria only if cobalt supply is adequate. The analogs differ generally by the nucleotide moiety of the molecule. In CBL, 5,6-dimethylbenzimidazole (5,6-DMB) is the base in the nucleotide moiety. The present study aimed to determine if a supplement of 5,6-DMB could increase utilization of dietary cobalt for synthesis of CBL and change ruminal fermentation, nutrient digestibility, omasal flow of nutrients and ruminal protozoa counts. Eight ruminally cannulated multiparous Holstein cows (mean±standard deviation=238±21 days in milk and 736±47 kg of BW) were used in a crossover design. Cows were randomly assigned to a daily supplement of a gelatin capsule containing 1.5 g of 5,6-DMB via the rumen cannula or no supplement. Each period lasted 29 days and consisted of 21 days for treatment adaptation and 8 days for data and samples collection. Five corrinoids, CBL and four cobamides were detected in the total mixed ration and the omasal digesta from both treatments. The dietary supplement of 5,6-DMB increased (P=0.02) apparent ruminal synthesis of CBL from 14.6 to 19.6 (s.e.m. 0.8) mg/day but had no effect (P>0.1) on apparent ruminal synthesis of the four analogs. The supplement of 5,6-DMB had no effect (P>0.1) on milk production and composition, or on protozoal count, ruminal pH and concentrations of volatile fatty acids and ammonia nitrogen in rumen content. The supplement had also no effect (P>0.1) on intake, omasal flow and apparent ruminal digestibility of dry matter, organic matter, NDF, ADF and nitrogenous fractions. Plasma concentration of CBL was not affected by treatments (P=0.98). Providing a preformed part of the CBL molecule, that is, 5,6-DMB, increased by 34% the apparent ruminal synthesis of CBL by ruminal bacteria but had no effect on ruminal fermentation or protozoa count and it was not sufficient to increase plasma concentrations of the vitamin. Even though

  9. NutriPhone: a mobile platform for low-cost point-of-care quantification of vitamin B12 concentrations.

    Science.gov (United States)

    Lee, Seoho; O'Dell, Dakota; Hohenstein, Jess; Colt, Susannah; Mehta, Saurabh; Erickson, David

    2016-06-15

    Vitamin B12 is necessary for formation of red blood cells, DNA synthesis, neural myelination, brain development, and growth. Vitamin B12 deficiency is often asymptomatic early in its course; however, once it manifests, particularly with neurological symptoms, reversal by dietary changes or supplementation becomes less effective. Access to easy, low cost, and personalized nutritional diagnostics could enable individuals to better understand their own deficiencies as well as track the effects of dietary changes. In this work, we present the NutriPhone, a mobile platform for the analysis of blood vitamin B12 levels in 15 minutes. The NutriPhone technology comprises of a smartphone accessory, an app, and a competitive-type lateral flow test strip that quantifies vitamin B12 levels. To achieve the detection of sub-nmol/L physiological levels of vitamin B12, our assay incorporates an innovative "spacer pad" for increasing the duration of the key competitive binding reaction and uses silver amplification of the initial signal. We demonstrate the efficacy of our NutriPhone system by quantifying physiologically relevant levels of vitamin B12 and performing human trials where it was used to accurately evaluate blood vitamin B12 status of 12 participants from just a drop (~40 μl) of finger prick blood.

  10. Recreational Nitrous Oxide Abuse-Induced Vitamin B12 Deficiency in a Patient Presenting with Hyperpigmentation of the Skin

    Directory of Open Access Journals (Sweden)

    Tsung-Ta Chiang

    2013-06-01

    Full Text Available Vitamin B12 deficiency causes skin hyperpigmentation, subacute combined degeneration of the spinal cord, and megaloblastic anemia. Although vitamin B12 deficiency rarely occurs in well-nourished, healthy, young people, nitrous oxide (N2O intoxication is an important cause of vitamin B12 deficiency in this cohort. N2O, a colorless gas used as an anesthetic since the late 19th century because of its euphoric and analgesic qualities, is now used as a recreational drug and is available via the Internet and at clubs. Here, we describe the case of a 29-year-old woman presenting with skin hyperpigmentation as her only initial symptom after N2O abuse for approximately 2 years. N2O intoxication-induced vitamin B12 deficiency was diagnosed based on the skin pigmentation that had manifested over the dorsa of her fingers, toes, and trunk, coupled with myeloneuropathy of the posterior and lateral columns, a low serum vitamin B12 level, an elevated serum homocysteine level, and the N2O exposure revealed while establishing the patient's history. Symptoms improved significantly with vitamin B12 treatment. We recommend that dermatologists consider N2O intoxication-induced vitamin B12 deficiency as a potential cause of skin hyperpigmentation and myeloneuropathy of the posterior and lateral columns in young, otherwise healthy patients. Failure to recognize this presentation may result in inappropriate treatment, thus affecting patients' clinical outcomes.

  11. Vitamin B12 and folate during pregnancy and offspring motor, mental and social development at 2 years of age.

    Science.gov (United States)

    Bhate, V K; Joshi, S M; Ladkat, R S; Deshmukh, U S; Lubree, H G; Katre, P A; Bhat, D S; Rush, E C; Yajnik, C S

    2012-04-01

    Insufficiency of vitamin B12 (B12) and folate during pregnancy can result in low concentrations in the fetus and have adverse effects on brain development. We investigated the relationship between maternal B12 and folate nutrition during pregnancy and offspring motor, mental and social development at two years of age (2 y). Mothers (n = 123) and their offspring (62 girls, 61 boys) from rural and middle-class urban communities in and around Pune city were followed through pregnancy up to 2 y. Maternal B12 and folate concentrations were measured at 28 and 34 weeks of gestation. At 2 y, the Developmental Assessment Scale for Indian Infants was used to determine motor and mental developmental quotients and the Vineland Social Maturity Scale for the social developmental quotient. Overall, 62% of the mothers had low B12 levels (development was associated with maternal folate at 28 and 34 weeks of gestation. Mental and social development quotients were associated positively with head circumference and negatively with birth weight. In addition, pregnancy B12 and folate were positively associated with mental and social development quotients. Maternal B12 and folate during intrauterine life may favorably influence brain development and function. Pregnancy provides a window of opportunity to enhance fetal psychomotor (motor and mental) development.

  12. Efficacy of vitamin B12 combined with metformin in treating type 2 diabetes and its effect on homocysteine

    Directory of Open Access Journals (Sweden)

    Na Geng

    2016-03-01

    Full Text Available Objective: To observe and analyze Vitamin B12 combined with metformin treat for the type 2 diabetes, which affect the homocysteine. Methods: 92 cases of type 2 diabetes were selected in our hospital for treatment and study from October 2014 to April 2014. All patients were randomly divided into control group (46 cases and observation group (46 cases. Treatment of patients in the control group: patients were treated by metformin; observation group patients: Take vitamin B12 to patients treated with metformin. Finally, patient outcomes, as well as vitamin B12 and homocysteine in patients before and after treatment were analyzed. Results: Before treatment, all patients vitamin B12 content difference comparisons were no significant differences (P>0.05. Patients were treated in January, June and 1 year after the vitamin B12 content of the observation group were significantly higher in patients with vitamin B12 levels of data compared to each other there was a significant difference (P0.05. Patients were treated in January, June and 1 year after the homocysteine content of the observation group were not significantly reduced, the control group of patients with homocysteine increased significantly (P<0.000 1. Conclusions: Vitamin B12 combined with metformin in type 2 diabetes treatment, can significantly increase a patient's body to control homocysteine, while the treatment effect is obvious, clinical recommendations widely implemented.

  13. Vitamin B12 deficiency results in severe oxidative stress, leading to memory retention impairment in Caenorhabditis elegans.

    Science.gov (United States)

    Bito, Tomohiro; Misaki, Taihei; Yabuta, Yukinori; Ishikawa, Takahiro; Kawano, Tsuyoshi; Watanabe, Fumio

    2017-04-01

    Oxidative stress is implicated in various human diseases and conditions, such as a neurodegeneration, which is the major symptom of vitamin B 12 deficiency, although the underlying disease mechanisms associated with vitamin B 12 deficiency are poorly understood. Vitamin B 12 deficiency was found to significantly increase cellular H 2 O 2 and NO content in Caenorhabditis elegans and significantly decrease low molecular antioxidant [reduced glutathione (GSH) and L-ascorbic acid] levels and antioxidant enzyme (superoxide dismutase and catalase) activities, indicating that vitamin B 12 deficiency induces severe oxidative stress leading to oxidative damage of various cellular components in worms. An NaCl chemotaxis associative learning assay indicated that vitamin B 12 deficiency did not affect learning ability but impaired memory retention ability, which decreased to approximately 58% of the control value. When worms were treated with 1mmol/L GSH, L-ascorbic acid, or vitamin E for three generations during vitamin B 12 deficiency, cellular malondialdehyde content as an index of oxidative stress decreased to the control level, but the impairment of memory retention ability was not completely reversed (up to approximately 50%). These results suggest that memory retention impairment formed during vitamin B 12 deficiency is partially attributable to oxidative stress. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Antibody biotechnology

    African Journals Online (AJOL)

    STORAGESEVER

    2009-07-06

    Jul 6, 2009 ... Another milestone in the history of antibodies was the work of Porter and Edelman ... transgenic animals (Lonberg et al., 1994; Green et al.,. 1994) or .... create and to screen human recombinant antibodies libraries, that is ...

  15. Fluorometric titration approach for calibration of quantity of binding site of purified monoclonal antibody recognizing epitope/hapten nonfluorescent at 340 nm.

    Science.gov (United States)

    Yang, Xiaolan; Hu, Xiaolei; Xu, Bangtian; Wang, Xin; Qin, Jialin; He, Chenxiong; Xie, Yanling; Li, Yuanli; Liu, Lin; Liao, Fei

    2014-06-17

    A fluorometric titration approach was proposed for the calibration of the quantity of monoclonal antibody (mcAb) via the quench of fluorescence of tryptophan residues. It applied to purified mcAbs recognizing tryptophan-deficient epitopes, haptens nonfluorescent at 340 nm under the excitation at 280 nm, or fluorescent haptens bearing excitation valleys nearby 280 nm and excitation peaks nearby 340 nm to serve as Förster-resonance-energy-transfer (FRET) acceptors of tryptophan. Titration probes were epitopes/haptens themselves or conjugates of nonfluorescent haptens or tryptophan-deficient epitopes with FRET acceptors of tryptophan. Under the excitation at 280 nm, titration curves were recorded as fluorescence specific for the FRET acceptors or for mcAbs at 340 nm. To quantify the binding site of a mcAb, a universal model considering both static and dynamic quench by either type of probes was proposed for fitting to the titration curve. This was easy for fitting to fluorescence specific for the FRET acceptors but encountered nonconvergence for fitting to fluorescence of mcAbs at 340 nm. As a solution, (a) the maximum of the absolute values of first-order derivatives of a titration curve as fluorescence at 340 nm was estimated from the best-fit model for a probe level of zero, and (b) molar quantity of the binding site of the mcAb was estimated via consecutive fitting to the same titration curve by utilizing such a maximum as an approximate of the slope for linear response of fluorescence at 340 nm to quantities of the mcAb. This fluorometric titration approach was proved effective with one mcAb for six-histidine and another for penicillin G.

  16. Antithyroid microsomal antibody

    Science.gov (United States)

    Thyroid antimicrosomal antibody; Antimicrosomal antibody; Microsomal antibody; Thyroid peroxidase antibody; TPOAb ... Granulomatous thyroiditis Hashimoto thyroiditis High levels of these antibodies have also been linked with an increased risk ...

  17. Effects of Chemical and Physical Enhancement Techniques on Transdermal Delivery of Cyanocobalamin (Vitamin B12 In Vitro

    Directory of Open Access Journals (Sweden)

    Ajay K. Banga

    2011-08-01

    Full Text Available Vitamin B12 deficiency, which may result in anemia and nerve damage if left untreated, is currently treated by administration of cyanocobalamin via oral or intramuscular routes. However, these routes are associated with absorption and compliance issues which have prompted us to investigate skin as an alternative site of administration. Delivery through skin, however, is restricted to small and moderately lipophilic molecules due to the outermost barrier, the stratum corneum (SC. In this study, we have investigated the effect of different enhancement techniques, chemical enhancers (ethanol, oleic acid, propylene glycol, iontophoresis (anodal iontophoresis and microneedles (soluble maltose microneedles, which may overcome this barrier and improve cyanocobalamin delivery. Studies with different chemical enhancer formulations indicated that ethanol and oleic acid decreased the lag time while propylene glycol based formulations increased the lag time. The formulation with ethanol (50%, oleic acid (10% and propylene glycol (40% showed the maximum improvement in delivery. Iontophoresis and microneedle treatments resulted in enhanced permeation levels compared to passive controls. These enhancement approaches can be explored further to develop alternative treatment regimens.

  18. Nitrous Oxide Abuse and Vitamin B12 Action in a 20-Year-Old Woman: A Case Report.

    Science.gov (United States)

    Duque, Miriam Andrea; Kresak, Jesse L; Falchook, Adam; Harris, Neil S

    2015-01-01

    Herein, we report a case of a 20-year-old (ethnicity not reported) woman with a history of nitrous oxide abuse and clinical symptoms consistent with spinal cord subacute combined degeneration with associated low serum concentrations of vitamin B12, elevated methylmalonic acid levels, and radiologic evidence of demyelination of the dorsal region of the spinal column. The health of the patient improved dramatically with B12 supplementation. In this case, we discuss the interaction of nitrous oxide with the enzymatic pathways involved in the biochemistry of vitamin B12. Copyright© by the American Society for Clinical Pathology (ASCP).

  19. The need for a sufficient number of low level sera in comparisons of different serum vitamin B12 assays

    International Nuclear Information System (INIS)

    Gijzen, A.H.J.; Kock, H.W. de; Meulendijk, P.N.; Schmidt, N.A.; Schopman, W.; Tertoolen, J.F.W.; Voogd, C.E.

    1983-01-01

    Eight radiochemical methods for the assay of vitamin B 12 in serum were compared with the microbiological assay with Lactobacillus leichmannii ATCC 7830 using 198 individual sera of patients. There was a good agreement between the results of most samples with some kits and the microbiological assay. However, especially in the sera of vitamin B 12 -deficient patients large discrepancies between the results could occur. These variations were due to both the kits used and the performance of the assays in different laboratories. A sufficient number of non-pooled sera of vitamin B 12 -deficient patients should be included in investigations to validate radiochemical methods. (Auth.)

  20. Elevated Plasma Vitamin B12 Levels as a Marker for Cancer

    DEFF Research Database (Denmark)

    Arendt, Johan Frederik Berg; Pedersen, Lars; Nexo, Ebba

    2013-01-01

    ) with 95% confidence intervals (CIs), stratified by plasma Cbl levels. All statistical tests were two-sided. RESULTS: We identified 333 667 persons without prevalent cancer and not receiving Cbl treatment. Six percent had Cbl levels greater than the upper reference limit (≥601 pmol/L). Cancer risk......BACKGROUND: A substantial proportion of patients referred for plasma vitamin B12 (cobalamin [Cbl]) measurement present with high Cbl levels, which have been reported in patients with different cancer types. However, the cancer risk among patients with newly diagnosed high Cbl levels has not been...... adequately examined. METHODS: We conducted this cohort study using population-based Danish medical registries. Patients referred for Cbl measurement with levels greater than the lower reference limit (≥200 pmol/L) were identified from the population of Northern Denmark during the period of 1998 to 2009 using...

  1. Structural and magnetic characterization of Co67Fe4Ni2Si15B12

    International Nuclear Information System (INIS)

    Manjura Hoque, S.; Khan, F.A.; Hakim, M.A.

    2007-01-01

    Soft magnetic properties of Co-based amorphous alloy of the composition Co 67 Fe 4 Ni 2 Si 15 B 12 have been investigated by isothermal heat treatment up to the conventional crystallization temperature. In the as-cast condition the Curie temperature of the sample is 272 deg. C and saturation magnetization is 74 emu/g. Magnetic properties undergo variation depending on the heat treatment temperature. For the heat treatment temperatures of around 420 and 490 deg. C, superior soft magnetic properties are obtained. For both the temperatures initial permeability, μ' reaches value up to ten times the value of permeability in the as-received samples. Annealing effect on giant magneto-impedance has been observed for the current-driving frequencies of 4.5 and 6 MHz. Field dependence of magneto-impedance shows hysteresis at low field, which is related to the changes in the magnetization process of the sample

  2. TOTAL PARENTERAL NUTRITION (TPN: ROLE OF RIBOFLAVIN (VITAMIN B2 AND CYANOCOBALAMIN (VITAMIN B12

    Directory of Open Access Journals (Sweden)

    Samina Shiekh

    2015-06-01

    Full Text Available Total parenteral nutrition (TPN replaces and maintains essential nutrients in patients in whom oral or tube feedings are contraindicated or inadequate. A nutritional assessment must be carried out before initiating TPN in order to determine nutritional needs and any metabolic changes due to the patient’s underlying condition, medications or concurrent therapies. In addition to carbohydrates, proteins and fats, certain amounts of micronutirents are also added to TPN solutions. These micronutrients include electrolytes, vitamins, and trace minerals. This review highlights some basic concepts regarding the use and formulation of TPNs along with their advantages and disadvantages and the importance of water soluble vitamins B2 and B12 in human nutrition.

  3. Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes

    DEFF Research Database (Denmark)

    Andersen, Christian Brix Folsted; Madsen, Mette; Storm, Tina

    2010-01-01

    Cobalamin (Cbl, vitamin B(12)) is a bacterial organic compound and an essential coenzyme in mammals, which take it up from the diet. This occurs by the combined action of the gastric intrinsic factor (IF) and the ileal endocytic cubam receptor formed by the 460-kilodalton (kDa) protein cubilin...... and the 45-kDa transmembrane protein amnionless. Loss of function of any of these proteins ultimately leads to Cbl deficiency in man. Here we present the crystal structure of the complex between IF-Cbl and the cubilin IF-Cbl-binding-region (CUB(5-8)) determined at 3.3 A resolution. The structure provides...... of how Cbl indirectly induces ligand-receptor coupling. Finally, the comparison of Ca(2+)-binding CUB domains and the low-density lipoprotein (LDL) receptor-type A modules suggests that the electrostatic pairing of a basic ligand arginine/lysine residue with Ca(2+)-coordinating acidic aspartates...

  4. Vitamin B12 Metabolism during Pregnancy and in Embryonic Mouse Models

    Directory of Open Access Journals (Sweden)

    Maira A. Moreno-Garcia

    2013-09-01

    Full Text Available Vitamin B12 (cobalamin, Cbl is required for cellular metabolism. It is an essential coenzyme in mammals for two reactions: the conversion of homocysteine to methionine by the enzyme methionine synthase and the conversion of methylmalonyl-CoA to succinyl-CoA by the enzyme methylmalonyl-CoA mutase. Symptoms of Cbl deficiency are hematological, neurological and cognitive, including megaloblastic anaemia, tingling and numbness of the extremities, gait abnormalities, visual disturbances, memory loss and dementia. During pregnancy Cbl is essential, presumably because of its role in DNA synthesis and methionine synthesis; however, there are conflicting studies regarding an association between early pregnancy loss and Cbl deficiency. We here review the literature about the requirement for Cbl during pregnancy, and summarized what is known of the expression pattern and function of genes required for Cbl metabolism in embryonic mouse models.

  5. Thyroid Antibodies

    Science.gov (United States)

    ... PF4 Antibody Hepatitis A Testing Hepatitis B Testing Hepatitis C Testing HER2/neu Herpes Testing High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV Antiretroviral Drug Resistance Testing, Genotypic HIV Viral Load HLA Testing HLA- ...

  6. Identification of ABC transporters acting in vitamin B12 metabolism in Caenorhabditis elegans.

    Science.gov (United States)

    McDonald, Megan K; Fritz, Julie-Anne; Jia, Dongxin; Scheuchner, Deborah; Snyder, Floyd F; Stanislaus, Avalyn; Curle, Jared; Li, Liang; Stabler, Sally P; Allen, Robert H; Mains, Paul E; Gravel, Roy A

    2017-12-01

    Vitamin B 12 (cobalamin, Cbl) is a micronutrient essential to human health. Cbl is not utilized as is but must go through complex subcellular and metabolic processing to generate two cofactor forms: methyl-Cbl for methionine synthase, a cytosolic enzyme; and adenosyl-Cbl for methylmalonyl-CoA mutase, a mitochondrial enzyme. Some 10-12 human genes have been identified responsible for the intracellular conversion of Cbl to cofactor forms, including genes that code for ATP-binding cassette (ABC) transporters acting at the lysosomal and plasma membranes. However, the gene for mitochondrial uptake is not known. We hypothesized that ABC transporters should be candidates for other uptake and efflux functions, including mitochondrial transport, and set out to screen ABC transporter mutants for blocks in Cbl utilization using the nematode roundworm Caenorhabditis elegans. Thirty-seven mutant ABC transporters were screened for the excretion of methylmalonic acid (MMA), which should result from loss of Cbl transport into the mitochondria. One mutant, wht-6, showed elevated MMA excretion and reduced [ 14 C]-propionate incorporation, pointing to a functional block in methylmalonyl-CoA mutase. In contrast, the wht-6 mutant appeared to have a normal cytosolic pathway based on analysis of cystathionine excretion, suggesting that cytosolic methionine synthase was functioning properly. Further, the MMA excretion in wht-6 could be partially reversed by including vitamin B 12 in the assay medium. The human ortholog of wht-6 is a member of the G family of ABC transporters. We propose wht-6 as a candidate for the transport of Cbl into mitochondria and suggest that a member of the corresponding ABCG family of ABC transporters has this role in humans. Our ABC transporter screen also revealed that mrp-1 and mrp-2 mutants excreted lower MMA than wild type, suggesting they were concentrating intracellular Cbl, consistent with the cellular efflux defect proposed for the mammalian MRP1 ABC

  7. Ultrasonographic evaluation to diagnose hepatic lipidosis in Egyptian Zaraibi goats with vitamin B12 deficiency

    Directory of Open Access Journals (Sweden)

    Sabry A. El-Khodery

    2011-01-01

    Full Text Available As little is known about the ultrasonographic features of hepatic lipidosis (white liver disease in goats, this study was undertaken to evaluate the use of ultrasound for the diagnosis of hepatic lipidosis associated with vitamin B12 (cyanocobalamin deficiency in Egyptian Zaraibi goats. A total of 38 goats (28 with weight loss, diarrhoea and anaemia and 10 clinically healthy were studied. Twenty-one goats were demonstrated to have cobalt and cyanocobalamin deficiency (0.33 ± 0.12 μmol/l and 0.17 ± 0.10 μg/l, respectively. Goats were examined with a real-time ultrasound system using a 5-MHz convex transducer. Ultrasound-guided liver biopsies and blood samples were obtained from each animal at examination. Based on the histopathological findings, diseased goats were classified as having mild (n = 6, moderate (n = 6 or severe lipidosis (n = 9. Ultrasonographic-hepatic changes were recorded in 19 (90.4% out of 21 goats. Severe lipidosis showed diffuse hyper-echogenicity of hepatic parenchyma. However, focal hyper-echoic lesions with various shapes, sizes and positions were visualized in mild and moderate lipidosis. Liver size increased significantly (P < 0.05 in severely affected goats compared with the controls. Histopathologically, macrovacuolations, congestion of hepatic sinusoids and infiltration of the portal area with inflammatory cells and connective tissues were evident in moderate and severely affected cases. There were varying degrees of anaemia, hypoglycemia and hypoproteinemia with significant increases (P < 0.05 of aspartate aminotransferase (AST and alkaline phosphatase (ALP in diseased animals compared with the controls. In conclusion, ultrasound may be a useful diagnostic tool in goats with suspected hepatic lipidosis associated with vitamin B12 deficiency.

  8. Minor displacements in the insertion site provoke major differences in the induction of antibody responses by chimeric parvovirus-like particles

    DEFF Research Database (Denmark)

    Rueda, P.; Hurtado, A.; del Barrio, M.

    1999-01-01

    inserted into these positions was well recognized by the specific monoclonal antibody C3 by immunoelectron microscopy. BALB/c mice immunized with these chimeric C3:B CPV:VLPs were able to elicit an strong neutralizing antibody response (>3 log(10) units) against poliovirus type 1 (Mahoney strain...

  9. Direct Rehydrogenation of LiBH4 from H-Deficient Li2B12H12−x

    Directory of Open Access Journals (Sweden)

    Yigang Yan

    2018-03-01

    Full Text Available Li2B12H12 is commonly considered as a boron sink hindering the reversible hydrogen sorption of LiBH4. Recently, in the dehydrogenation process of LiBH4 an amorphous H-deficient Li2B12H12−x phase was observed. In the present study, we investigate the rehydrogenation properties of Li2B12H12−x to form LiBH4. With addition of nanostructured cobalt boride in a 1:1 mass ratio, the rehydrogenation properties of Li2B12H12−x are improved, where LiBH4 forms under milder conditions (e.g., 400 °C, 100 bar H2 with a yield of 68%. The active catalytic species in the reversible sorption reaction is suggested to be nonmetallic CoxB (x = 1 based on 11B MAS NMR experiments and its role has been discussed.

  10. The clinical observation on the treatment of irradiated injuries of the skin and mucosa by using vitamin B12

    International Nuclear Information System (INIS)

    Ji, Hui; Li, Jianchao; Xie, Xiuzhen; Chen, Quiang; Yang, Yongguang

    1987-01-01

    A clinical study of the treatment of irradiated skin and mucosa injuries (40 cases). This paper introduces two methods of treating irradiated injuries of the skin and mucosa. By using Vitamin B 12 both externaly and applying in the mouth, we can stop the pain promptly, reduce the exudation, improve the growth of granulation and the healing of the ulcer especialy in the early acute stage. In addition Vitamin B 12 produces good effects on other kinds of skin injuries. Shu BaiKe considered that the skin had the same function as the liver, which includes various kinds of enzymes. We thought that using Vitamin B 12 externaly on skin injuries, it would be absorbed and join the RNA synthesizing process in the liver and skin. After applying Vitamin B 12 , the RNA content rose. The results of animal experiments coincided with clinial treatment. It clarified the mechanisms needed to treat the third degree acute irradiated skin injuries. (author)

  11. Radioisotope binding capacity of serum for folic acid, vitamin B12 and ferritin in hematologic and rheumatologic patients

    International Nuclear Information System (INIS)

    Ringelhann, B.; Revicky, A.; Arvai, I.; Megyeri, A.; Goemoer, B.; Josfay, L.; Csak, E.

    1980-01-01

    Folic acid, vitamin B 12 and ferritin levels were determined by radioimmunoassay in patients suffering from hemic and rheumatic diseases, resp. Compared to the controls the folic acid levels were lower in some cases, the deficiency of folic acid absorption and distribution possibly being caused by the disease. Vitamin B 12 was only slightly decreased. In ankylosing spondylitis the transferrin level was similar to that of the controls, but in rheumatoid arthritis and in patients suffering from various diseases it was increased

  12. Cobalamin (Vitamin B12) Role on the Biochemical, Histological and Teratological Changes Induced in Diabetic Irradiated Pregnant Rats

    International Nuclear Information System (INIS)

    Ramadan, F.L.

    2013-01-01

    Vitamin B 12 called Cobalamin, is a water soluble vitamin with a key role in the normal function of the brain, nervous system, cell division and for the formation of blood. It is normally involved in the metabolism of every cell of the human body especially affecting DNA synthesis and regulation, fatty acid synthesis and energy production.The aim of the present study was to evaluate the role of vitamin B 12 intake on radiation induced damage in diabetic mothers.Diabetes was induced in female rats by intra-peritoneal injection of alloxan 150 mg/kg b.wt. dissolved in saline. Pregnant diabetic mothers were received vitamin B 12 0.1 mg/100 g b.wt. from the 1st up to 19th day of gestation. Meanwhile, pregnant diabetic rats were exposed to 0.6 Gy on the 7th and the 14th days of gestation. The increased incidence of malformations in diabetic pregnancy with an excess of free oxygen radicals in the embryos was recorded .Vitamin B12 supplementation to diabetic mother ameliorated radiation-induced damage which was obvious by diminishing the increase in glucose level, improving serum insulin level, glycogen content in the liver and ameliorating the decrease in glutathione (GSH) content in the liver of pregnant rats and their fetuses.In addition, vitamin B 12 treatment improved the decrease in red blood cells (RBCs), white blood cells (WBCs) and hemoglobin (Hb) of fetuses and DNA content in the liver tissues. Moreover, vitamin B 12 treatment lead to the regeneration of normal architecture of maternal and fetuses hepatic cells and blood vessels. It could be concluded that vitamin B 12 supplementation to diabetic mothers ameliorated the radiation effect which induced biochemical, histochemical, histological and teratological disorders.Furthermore, the results obtained showed that vitamin B 12 administration caused a protection to diabetic pregnant rats against embryo malformations induced by gamma rays

  13. Preparation and Characterization of Cyanocobalamin (Vit B12 Microemulsion Properties and Structure for Topical and Transdermal Application

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    Anayatollah Salimi

    2013-07-01

    This study showed that both microemulsions provided good solubility of Vit B12 with a wide range of internal structure. Low water solubilization capacity is a common property of microemulsions that can affect drug release and permeability through the skin. Based on Vit B12 properties, specially, intermediate oil and water solubility, better drug partitioning into the skin may be obtained by traditional formulations with wide range of structure and high amount of free and bounded water.

  14. Investigation of the binding affinity in vitamin B12-Bovine serum albumin system using various spectroscopic methods

    Science.gov (United States)

    Makarska-Bialokoz, Magdalena

    2017-09-01

    The binding affinity between vitamin B12 (VitB12) and bovine serum albumin (BSA) has been investigated in aqueous solution at pH = 7.4, employing UV-vis absorption and steady-state, synchronous and three-dimensional fluorescence spectra techniques. Representative effects noted for BSA intrinsic fluorescence resulting from the interactions with VitB12 confirm the formation of π-π stacked non-covalent and non-fluorescent complexes in the system VitB12-BSA. All the determined parameters, the binding, fluorescence quenching and bimolecular quenching rate constants (of the order of 104 L mol- 1, 103 L mol- 1 and 1011 L mol- 1 s- 1, respectively), as well as Förster resonance energy transfer parameters validate the mechanism of static quenching. The interaction with VitB12 induces folding of the polypeptide chains around Trp residues of BSA, resulting in a more hydrophobic surrounding. Presented outcomes suggest that the addition of VitB12 can lead to the more organized BSA conformation and its more folded tertiary structure, what could influence the physiological functions of bovine serum albumin, notably in case of its overuse or abnormal metabolism.

  15. Effects of γ-irradiation and cooking on vitamins B6 and B12 in grass prawns (Penaeus monodon)

    International Nuclear Information System (INIS)

    Hau, L.-B.; Liew, M.-S.

    1993-01-01

    The effects of radiation doses, irradiation temperature and a combined treatment of irradiation and cooking on the vitamin B 6 and B 12 contents of grass prawns have been studied. Grass prawns were irradiated at refrigerated (4 o C) or frozen (-20 o C) temperatures with different doses. A domestic cooling procedure was followed after irradiation. The changes in vitamins B 6 and B 12 of both raw and cooked grass prawns were evaluated. Results showed no significant changes of vitamin B 6 and B 12 in grass prawns with a radiation dose up to 7 kGy at either 4 o C or -20 o C. Irradiation at 4 o C caused more destruction of vitamin B 12 but not vitamin B 6 than did irradiation at -20 o C in grass prawns. There was significant destruction of both vitamins B 6 and B 12 in unirradiated samples during cooking. The introduction of the irradiation process before cooking had no effect on either vitamin. These results indicate that the loss of vitamins B 6 and B 12 in the combined treatments was caused mainly by thermal destruction. (author)

  16. Fluorescent carbon dots nanosensor for label-free determination of vitamin B12 based on inner filter effect

    Science.gov (United States)

    Ding, Longhua; Yang, Hongmei; Ge, Shenguang; Yu, Jinghua

    2018-03-01

    A simple and effective fluorescent assay for the determination of vitamin B12 was developed. In this study, carbon dots (CDs) were prepared by one-pot hydrothermal method and directly used as a fluorophore in the inner filter effect (IFE). Both of the maximum absorption peak of vitamin B12 and excitation maxima of CDs are located at 360 nm, hence, the excited light of CDs can be absorbed by vitamin B12, resulting in the fluorescence reduction of CDs. And the fluorescence intensity of CDs decreases with the increasing concentration of vitamin B12. This IFE-based sensing strategy shows a good linear relationship between the normalized fluorescence intensity and the concentration of vitamin B12 ranging from 0 to 60 μM, with a limit of detection (LOD) of 0.1 μM at a signal-to-noise ratio of 3. Furthermore, this proposed approach was successfully applied to vitamin B12 sensing in injections. This IFE sensing platform based on various fluorescent nanomaterials has a high promise for the detection of other biomolecules due to its inherent convenience.

  17. Spectroscopic investigations of the B12-binding subunit of glutamate mutase: refined solution structure of the complex with the B12-nucleotide, dynamics and binding studies with two corrinoid cofactors

    International Nuclear Information System (INIS)

    Eichmueller, C.

    2002-06-01

    Glutamate mutase is an enzyme isolated from Clostridium tetanomorphum and Clostridium cochlearum. It catalyses the reversible rearrangement of (2S)-glutamate to (2S,3S)-3-methylaspartate. Coenzyme B12 is required as cofactor for an active enzyme, as the first step of the catalytic cycle is the homolytic cleavage of the cobalt-carbon bond. The rearrangement itself follows a radical mechanism. The holoenzyme is an alpha2beta2 heterotetramer containing two identical catalytic and two B12 binding domains, as well as two coenzyme B12 molecules. The smaller B12 binding domain from Clostridium tetanomorphum, MutS, is known to bind coenzyme B12 in its unusual 'base-off' form. A conserved histidine residue coordinates to the cobalt atom instead of the normally coordinated dimethlybenzimidole in free coenzyme B12. In the present work a refined solution structure of the B12 binding subunit from Clostridium tetanomorphum (MutS) in complex with the detached nucleotide loop of coenzyme B12 has been determined using nuclear magnetic resonance. The found topology is almost identical to the crystal structure of glutamate mutase from C.cochlearum [Reitzer et al., 1999], in contrast to the solution structures obtained for apo-MutS [Hoffmann et al., 2001; Tollinger et al., 1998] and apo-GlmS [Hoffmann et al., 1999]. In these two structures a helix at one side of the B12 nucleotide loop binding pocket is mostly unstructured and shows motions on a microsecond to millisecond timescale. The previously found stabilization of this helix upon B12-nucleotide binding [Tollinger et al., 2001] was confirmed using 13C and 15N labeled MutS. Some differences are found in the structure of the binding pocket and the bound nucleotide loop compared to the crystal structure. This indicates that additional conformational changes occur upon binding of the corrin ring of coenzyme B12. NMR-relaxation measurements performed on apo-MutS showed interesting slow molecular motions not only in the mainly

  18. USAGE OF MONOCLONAL ANTIBODIES FOR DETERMINATION OF LOCALIZATION OF ANTIGENIC DETERMINANTS AND FIBRIN POLYMERIZATION SITES WITHIN FIBRINOGEN AND FIBRIN MOLECULES AND THEIR APPLICATION IN TEST--SYSTEMS FOR DIAGNOSTICS AND THE THREAT OF THROMBUS FORMATION

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    E. V. Lugovskoi

    2013-08-01

    Full Text Available It was shown by monoclonal antibodies that B?N-region of fibrin desA molecule (B?1-53 comprises the polymerization site including the peptide bond B?14-15. This site participates in the second stage of fibrin polymerization — lateral association of protofibrils. In the B?15-53 fragment was also found the site called «C», which together with the site «A» participate in the first stage of polymerization — the protofibrils formation. The model of the primary intermolecular interaction of fibrin was designed. It was found by monoclonal antibodies II-4d the site («c» in the N-terminal half of ? chain of the fibrin D-region. This site participates in the protofibrils formation and is complement to site «C» as we assume. We have discovered two neoantigenic determinants. One of these determinants exposes within the coiledcoil fragment B?126-135 of fibrin as a result of fibrinopeptide A splitting off from fibrinogen by thrombin. The structural rearrangements discovered in this site of the fibrin molecule are necessary for the following protofibrils lateral association. The second neoantigenic determinant is localized in the fragment B?134-190 of D-dimer formed after plasmin degradation of fibrin stabilized by FXIIIa. We have obtained the fibrin-specific monoclonal antibodie FnI-3C to the first determinant and D-dimer-specific mAb III-3b to the second one. Three monoclonal antibodies were obtained against the ?C-region of fibrin(ogen molecule. It has been experimentally shown by of one of them that ?C-domains is connected with the fibrinopeptides B in fibrinogen and fibrin desA molecules, but removes from the core of the molecules after fibrinopeptides B splitting off by thrombin. Two other monoclonal antibodies specifically inhibit the fibrin polymerization by blocking two unknown polymerization sites within the ?C-region. The test-systems for the soluble fibrin and D-dimer quantification in human blood plasma were designed on the basis of

  19. Exceptional Structural Compliance of the B12F122- Superweak Anion.

    Science.gov (United States)

    Peryshkov, Dmitry V; Strauss, Steven H

    2017-04-03

    The single-crystal X-ray structures, thermogravimetric analyses, and/or FTIR spectra of a series of salts of the B 12 F 12 2- anion and homoleptic Ag(L) n + cations are reported (L = CH 2 Cl 2 , n = 2; L = PhCH 3 , n = 3; L = CH 3 CN; n = 2-4; L = CO, n = 1, 2). The superweak-anion nature of B 12 F 12 2- (Y 2- ) was demonstrated by the rapid reaction of microcrystalline Ag 2 (Y) with 1 atm of CO to form a nonclassical silver(I) carbonyl compound with an FTIR ν(CO) band at 2198 cm -1 (and with the proposed formula [Ag(CO) n ] 2 [Y]). In contrast, microcrystalline Ag 2 (B 12 Cl 12 ) did not exhibit ν(CO) bands and therefore did not form Ag(CO) + species, even after 32 h under 24 atm of CO. When Ag 2 (Y) was treated with carbon monoxide pressures higher than 1 atm, a new ν(CO) band at 2190 cm -1 appeared, which is characteristic of a Ag(CO) 2 + dicarbonyl cation. Both Ag 2 (CH 3 CN) 8 (Y) and Ag 2 (CH 3 CN) 5 (Y) rapidly lost coordinated CH 3 CN at 25 °C to form Ag 2 (CH 3 CN) 4 (Y), which formed solvent-free Ag 2 (Y) only after heating above 100 °C. Similarly, Ag 2 (PhCH 3 ) 6 (Y) rapidly lost coordinated PhCH 3 at 25 °C to form Ag 2 (PhCH 3 ) 2 (Y), which formed Ag 2 (Y) after heating above 150 °C, and Ag 2 (CH 2 Cl 2 ) 4 (Y) rapidly lost three of the four coordinated CH 2 Cl 2 ligands between 25 and 100 °C and formed Ag 2 (Y) when it was heated above 200 °C. Solvent-free Ag 2 (Y) was stable until it was heated above 380 °C. The rapid evaporative loss of coordinated ligands at 25 °C from nonporous crystalline solids requires equally rapid structural reorganization of the lattice and is one of three manifestations of the structural compliance of the Y 2- anion reported in this work. The second, more quantitative, manifestation is that Ag + bond-valence sums for Ag 2 (CH 3 CN) n (Y) are virtually constant, 1.20 ± 0.03, for n = 8, 5, 4, because the Y 2- anion precisely compensated for the lost CH 3 CN ligands by readily forming the necessary number of weak

  20. Purification of immunoreactive radiolabeled moniclonal antibodies with anti-iodiotypic moniclonal antibodies

    International Nuclear Information System (INIS)

    Temponi, M.; Pupa, S.; Ferrone, S.

    1990-01-01

    A method is described to purify immunoreactive moniclonal antibodies from radiolabeled monoclonal antibody preparations. The method is based on incubation of radiolabeled monoclonal antibodies with insolubilized anti-idiotypic monoclonal antibodies to idiotopes within the antigen-combining site of monoclonal antibodies to be purified an elution of bound monoclonal antibodies with a low pH buffer. The immunoreactive fraction of the purified monoclonal antibodies was at least 82%; the yeald was at least 73%. The purification procedure did not cause any detectable change in the affinity constant of the eluted monoclonal antibodies. The method is simple and rapid; the requirement for anti-idiotypic monoclonal antibodies to idiotopes within the antigen-combining site of the antibodies to be purified is not likely to represent a major limitation in the broad application of the present method, since the hybridoma technology has greatly facilitated the development of anti-idiotypic monoclonal antibodies. (author). 12 refs.; 4 figs.; 1 tab

  1. Screening of the vitamin B12 status in an urban population sample from Romania: a pilot study

    Directory of Open Access Journals (Sweden)

    Crăciun Elena C.

    2014-06-01

    Full Text Available Scopul acestui studiu a fost evaluarea statusului vitaminei B12 într-un eşantion al populaţiei urbane adulte din România. În studiu au fost incluşi 80 de subiecţi non-vegetarieni, cu vârste cuprinse între 19 şi 74,6 ani, care nu au utilizat suplimente de vitamina B12 sau alimente fortificate cu vitamina B12. Dozarea vitaminei B12 serice s-a realizat prin metoda imunochimică cu detecţie prin chemiluminiscenţă pe analizor Elecsys 2010 (Roche. Concentraţia serică a vitaminei B12 s-a încadrat în intervalul de referinţă (191-663 pg/ml la 93,75% (95% CI 86,2-97,3% din subiecţi. La aceşti subiecţi nu s-au evidenţiat corelaţii seminificative statistic între concentraţia serică a vitaminei B12 şi vârsta subiecţilor sau concentraţia hemoglobinei. Nu s-au găsit nici diferenţe semnificative (p>0.05 ale statusului vitaminic la femei faţă de bărbaţi. Concentraţia serică a vitaminei B12 s-a situat sub limita inferioară a intervalului de referinţă la 5% (95%CI 1,96-12,16% din subiecţii investigaţi, fiind asociată tratamentului cu contraceptive orale, inhibitori ai pompei de protoni (IPP respectiv sindromului de colon iritabil. La un număr mare de subiecţi cu vârsta sub 50 de ani, concentraţia serică a vitaminei B12 s-a încadrat în limitele corespunzătoare statusului marginal. Rezultatele studiului sugerează necesitatea efectuării screeningului statusului vitaminei B12 la întreaga populaţie, importanţa identificării factorilor responsabili de prevalenţa crescută a statusului marginal şi importanţa monitorizării statusului vitaminei B12 la subiecţii care fac tratament îndelungat cu unele medicamente.

  2. Vitamin B12 deficiency - a major cause of megaloblastic anaemia in patients attending a tertiary care hospital

    International Nuclear Information System (INIS)

    Iqbal, S.P.; Kakepoto, G.N.; Iqbal, S.P.

    2009-01-01

    Folate and vitamin B12 deficiencies have been known to cause megaloblastic anaemia. Since the deficiencies of these two vitamins are very common in Pakistani population, it would be imperative to investigate their role in causing megaloblastic anaemia. The objective of this study was to find out the contribution of folate and vitamin B12 deficiencies in causing megaloblastic anaemia in our patient population. Methods: In this retrospective cohort study, clinical records of 220 patients (101 females and 119 males with an age range of 1 - 80 years) who presented themselves with macrocytic anaemia at the Aga Khan University Hospital were collected. Data pertaining to complete blood count and serum levels of folate and vitamin B12 were analysed. Results: The mean haemoglobin (Hb) level was 6.8 +- 0.2 gm/dl. Sixty-nine percent of the patients had severe anaemia (Hb<8 gm/dl). Mean +- SEM values of haemoglobin, serum folate and serum B12 were not significantly different between males and females (Hb 6.4 +- 0.3 gm/dl vs 6.3 +- 0.3 gm/dl; folate 6.9 +- 0.8 mu g/ml vs 7.8 +- 1 mu g/ml; B12 259 +- 65 mu g/ml vs 225 +- 45 mu g/ml, respectively). Linear regression analysis showed that serum folate was inversely related with the mean corpuscular volume (MCV, p=0.04). Spearman's correlation analysis indicated an inverse mild association between MCV and serum folate (correlation coefficient= -0.18). Folate deficiency was 43.4%, while vitamin B12 deficiency was 78.5% in these patients. Seventy-one percent of folate-deficient patients had vitamin B12 deficiency as well, while 26.1% of patients with B12 deficiency had a co-occurrence of folate deficiency. Conclusion: Vitamin B12 deficiency appears to be the major factor leading to megaloblastic anaemia in our study population. Inadequate dietary intake, over-cooking of our food and poor absorption might be contributing to high prevalence of vitamin B12 deficiency in this population. (author)

  3. Multivitamin Use and Serum Vitamin B12 Concentrations in Older-Adult Metformin Users in REGARDS, 2003-2007.

    Science.gov (United States)

    Kancherla, Vijaya; Garn, Joshua V; Zakai, Neil A; Williamson, Rebecca S; Cashion, Winn T; Odewole, Oluwaseun; Judd, Suzanne E; Oakley, Godfrey P

    2016-01-01

    Metformin, an insulin-sensitizing drug, is a first line treatment for type 2 diabetes. Long-term use of metformin has been associated with subsequent reductions in vitamin B12 concentrations. The objective of our study was to determine whether metformin use is associated with lower serum vitamin B12 concentrations in older adults, and whether concurrent use of multivitamins modifies this association. We examined 2,510 participants aged 50 years and over, participating in the national population-based Reasons for Geographic And Racial Differences in Stroke (REGARDS) Study. Multivariable linear and logistic regression models were used to assess associations between multivitamin use and serum vitamin B12 concentrations. We estimated adjusted odds ratios (aOR)s and confidence intervals (CI)s. Results were stratified by three metformin/diabetes sub-groups: 1) participants with diabetes who were metformin users; 2) participants with diabetes who were not metformin users; and 3) participants without diabetes. We found that diabetic metformin users had significantly lower geometric mean serum B12 concentrations (409 pmol/L) than the group with diabetes not taking metformin (485 pmol/L; PL; P = 0.02). The geometric mean serum B12 concentrations were greater for multivitamin users (509 pmol/L) compared to those who did not use multivitamins (376 pmol/L; pvitamin B12 concentrations that were 50% (or 161 pmol/L) higher, compared to those not using multivitamins. Among metformin users, multivitamin use was associated with lower prevalence of combined low and borderline vitamin B12 concentrations (aOR = 0.14; 95% CI = 0.04, 0.54) compared to those not using multivitamins. In conclusion, metformin use was associated with lower geometric mean serum vitamin B12 concentrations among diabetic older adults compared to their counterparts. Concurrent multivitamin use may potentially protect against low or borderline vitamin B12 concentrations in long-term metformin users. Additional

  4. Studies on the biosynthesis of vitamin B2 and vitamin B12

    International Nuclear Information System (INIS)

    Chen, H.C.

    1988-01-01

    Feeding experiments with Ashbya gossypii followed by NMR analysis of the resulting riboflavin showed incorporation of deuterium from D-[2- 2 H]ribose at C-2' and from D-[1- 2 H]ribose in the pro-R position at C-1' of the ribityl side chain. The results rule out an Amadori rearrangement mechanism for the reduction of the ribosylamino to the ribitylamino linkage and point to formation of a Schiff base that is reduced stereospecifically opposite to the face from which the oxygen has departed. As prerequisite for the analysis, the 1 H NMR signals for the pro-R and pro-S hydrogens at C-1' of riboflavin and its tetraacetate were assigned with the aid of synthetic stereospecifically deuteriated samples. Feeding experiments with Propionibacterium shermianii followed by NMR analysis of the resulting vitamin B 12 showed: (1) 5-methylbenzimidazole (5MBI) incorporated and only one regioisomer (B6-demethylcyanocobalamin)formed. (2) 8-demethylriboflavin incorporated and the same regioisomer was obtained as 5MBI experiment. (3) [1'- 13 C, 5- 15 N]riboflavin incorporated and 13 C-NMR showed that 13 C at the B2 position of cyanocobalamin coupled to both adjacent nitrogen-15 atoms at about the same ratio

  5. Reductive dehalogenase structure suggests a mechanism for B12-dependent dehalogenation.

    Science.gov (United States)

    Payne, Karl Ap; Quezada, Carolina P; Fisher, Karl; Dunstan, Mark S; Collins, Fraser A; Sjuts, Hanno; Levy, Colin; Hay, Sam; Rigby, Stephen Ej; Leys, David

    2015-01-22

    Organohalide chemistry underpins many industrial and agricultural processes, and a large proportion of environmental pollutants are organohalides. Nevertheless, organohalide chemistry is not exclusively of anthropogenic origin, with natural abiotic and biological processes contributing to the global halide cycle. Reductive dehalogenases are responsible for biological dehalogenation in organohalide respiring bacteria, with substrates including polychlorinated biphenyls or dioxins. Reductive dehalogenases form a distinct subfamily of cobalamin (B12)-dependent enzymes that are usually membrane associated and oxygen sensitive, hindering detailed studies. Here we report the characterization of a soluble, oxygen-tolerant reductive dehalogenase and, by combining structure determination with EPR (electron paramagnetic resonance) spectroscopy and simulation, show that a direct interaction between the cobalamin cobalt and the substrate halogen underpins catalysis. In contrast to the carbon-cobalt bond chemistry catalysed by the other cobalamin-dependent subfamilies, we propose that reductive dehalogenases achieve reduction of the organohalide substrate via halogen-cobalt bond formation. This presents a new model in both organohalide and cobalamin (bio)chemistry that will guide future exploitation of these enzymes in bioremediation or biocatalysis.

  6. Development of an electrochemical biosensor for vitamin B12 using D-phenylalanine nanotubes

    Science.gov (United States)

    Moazeni, Maryam; Karimzadeh, Fathallah; Kermanpur, Ahmad; Allafchian, Alireza

    2018-01-01

    In the past decades, biosensors are one of the most interesting topics among researchers and scientist. The biosensors are used in several applications such as determining food quality, control and diagnose clinical problems and metabolic control. Therefore, many efforts have been carried out to design and develop a new generation of these systems. On the other hand nanotechnology by improving the performance of sensors has created an excellent outlook. Using nanomaterials such as nanoparticles, nanotubes, nanowires, and nanorods in diagnostic tools has been significantly increased accuracy, sensitivity and improved detection limits in sensors. In this study, the one-dimensional morphology of the D-phenylalanine was assembled on the surface of the gold electrode. In the next step electrochemical performance of the modified electrode was investigated by Cyclic Voltammetry (CV), Electrochemical Impedance Spectroscopy (EIS) and Differential Pals Voltammograms (DPV). Finally, by measuring the different concentrations of vitamin B12, the detection limit of the biosensor was obtained 1.6 µM.

  7. Chronic transgenerational vitamin B12 deficiency of severe and moderate magnitudes modulates adiposity-probable underlying mechanisms.

    Science.gov (United States)

    Ghosh, Shampa; Sinha, Jitendra Kumar; Muralikrishna, Bojanapalli; Putcha, Uday Kumar; Raghunath, Manchala

    2017-05-06

    We have demonstrated previously that severe but not moderate vitamin B12 deficiency altered body composition and induced adiposity in female C57BL/6 mice. This study aims to elucidate the effects of chronic transgenerational dietary vitamin B12 restriction on body composition and various biochemical parameters in the F1 generation offspring of our mouse models of severe and moderate vitamin B12 deficiency established earlier. Female weanling C57BL/6 mice received, ad libitum, for 4 weeks a (i) control diet, (ii) vitamin B12-restricted diet with pectin as dietary fiber (severely deficient diet), or (iii) vitamin B12-restricted diet with cellulose as dietary fiber (moderately deficient diet) and then mated with control males. The offspring of control and severely deficient dams continued on the respective diets of their mothers. Few moderately deficient dams were rehabilitated to control diet from parturition and their pups were weaned to control diet. Also, some offspring born to moderately B12 deficient dams were weaned to control diet, while others continued on the same diet as their mothers. Various parameters were determined in the F1 offspring after 12 and 36 weeks of feeding. The results indicate that both severe and moderate maternal vitamin B12 restrictions were associated with accelerated catch-up growth, increased body fat percentage, visceral adiposity, dyslipidemia, fasting hyperglycemia and insulin resistance in the F1 offspring. Inflammation, increased glucocorticoid and oxidative stress and poor antioxidant defence probably underlie these adverse effects. Rehabilitation from parturition but not weaning was beneficial in delaying the onset of the adverse outcomes in the offspring. © 2016 BioFactors, 43(3):400-414, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  8. Investigation for preparation and production of radio-kit Vitamin B12 with med-grade (part 1)

    International Nuclear Information System (INIS)

    Ghafourian, H.; Mazaheri Tehrani, M.; Ezadyar, A.; Shams Rafiee, M.; Nazari, A.

    2005-01-01

    Labelled vitamins B 12 with 58 Co is one of the important ingredients of the diagnostic Kits for diagnosis of patients affected by anemia. The insufficient absorption of vitamin B 12 is one of the causes of anemia in humans and one of the accurate methods for measurement of the absorbed vitamin B 12 is application of labelled vitamin B 12 with the cobalt-58 radioisotope.The isolation and purifications of the labelled vitamin B 12 from fermentation medium of streptomyces olivaceus is an essential process for kit preparation. The first experiment in this research was isolation and purification of B 12 using different resins with the solution of cyanocobalamin containing cobalt-59, produced by this bacterium. After investigation and pre-feasibility experiments two non-polar resins XAD-4 and XAD-7 were selected. The results that obtained from different experiments on XAD-4 and XAD-7 showed that XAD-4 is much better than the latter one due to immobilization of cobalamin. The isolation of vitamin B1 2 on XAD-4 column was achieved by different solvents such as methanol, ethanol and isopropanol in different concentration ratios. The results of Thin Layer Chromatography showed that the best eluant solutions for desorbtion of cobalamin from XAD-4 column are solvents such as methanol,ethanol and isopropanol with the maximum concentration of vitamin B 12 in the concentration ranges of 25 up to 50 per-cent, 30 up to 40 per-cent and 10 per-cent, respectively. Cobalamin was collected in aceton and crystallized in low temperature

  9. EFICIENTIZAREA OBŢINERII SEDIMENTELOR FURAJERE B12 -VITAMINIZATE DIN APE REZIDUALE AGROINDUSTRIALE: 2. MODIFICĂRI ALE UTILAJULUI

    Directory of Open Access Journals (Sweden)

    Victor COVALIOV

    2017-03-01

    Full Text Available Prin modificări constructive ale dispozitivelor bioreactorului şi soluţii noi: separarea zonelor acetogenă şi meta­no­genă în interiorul bioreactorului, recircularea CO2 şi suplimentarea acestuia cu H2 exogen, adsorbţia vitaminei B12 din lichidul postfermentare cu diatomită s-a obţinut ridicarea conţinutului de vitamina B12 în sedimentele epurării fermentativ–metanogene (anaerobe a borhotului postalcoolic până la calitatea de con­centrat furajer B12-vitaminizat, concomitent cu intensificarea producerii biometanului, ca elemente ale ridicării eficienţei ecologo-economice a epurării anaerobe a borhotului.MORE EFFICIENT PRODUCITON OF VITAMINIZED FORAGE SLUDGE CONTAINING B12 FROM AGRO-INDUSTRIAL WASTES: 2. EQUIPMENT MODIFICAITON The increase in vitamin B12 contents in the sludge was obtained resulted from the methanogenic (anaerobic digestion of post-distillery vinasse, through the design modifications of bioreactor interiour, CO2 re-circulation and its interaction with additionally dosed exogenic hydrogen. Vitamin B12 was further adsorbed on diatomite surface from the post-digestion liquid, which made it possible to produce the cattle forage concentrate enriched with vitamin B12. At the same time, biomethane production was intensified, being the element of ecologically-economic efficiency of anaerobic treatment of vinasse (agro-industrial waste.

  10. Crystal structure of snake venom acetylcholinesterase in complex with inhibitory antibody fragment Fab410 bound at the peripheral site: evidence for open and closed states of a back door channel.

    Science.gov (United States)

    Bourne, Yves; Renault, Ludovic; Marchot, Pascale

    2015-01-16

    The acetylcholinesterase found in the venom of Bungarus fasciatus (BfAChE) is produced as a soluble, non-amphiphilic monomer with a canonical catalytic domain but a distinct C terminus compared with the other vertebrate enzymes. Moreover, the peripheral anionic site of BfAChE, a surface site located at the active site gorge entrance, bears two substitutions altering sensitivity to cationic inhibitors. Antibody Elec410, generated against Electrophorus electricus acetylcholinesterase (EeAChE), inhibits EeAChE and BfAChE by binding to their peripheral sites. However, both complexes retain significant residual catalytic activity, suggesting incomplete gorge occlusion by bound antibody and/or high frequency back door opening. To explore a novel acetylcholinesterase species, ascertain the molecular bases of inhibition by Elec410, and document the determinants and mechanisms for back door opening, we solved a 2.7-Å resolution crystal structure of natural BfAChE in complex with antibody fragment Fab410. Crystalline BfAChE forms the canonical dimer found in all acetylcholinesterase structures. Equally represented open and closed states of a back door channel, associated with alternate positions of a tyrosine phenol ring at the active site base, coexist in each subunit. At the BfAChE molecular surface, Fab410 is seated on the long Ω-loop between two N-glycan chains and partially occludes the gorge entrance, a position that fully reflects the available mutagenesis and biochemical data. Experimentally based flexible molecular docking supports a similar Fab410 binding mode onto the EeAChE antigen. These data document the molecular and dynamic peculiarities of BfAChE with high frequency back door opening, and the mode of action of Elec410 as one of the largest peptidic inhibitors targeting the acetylcholinesterase peripheral site. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Association of Vitamin B12 with Pro-Inflammatory Cytokines and Biochemical Markers Related to Cardiometabolic Risk in Saudi Subjects

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    Nasser M. Al-Daghri

    2016-09-01

    Full Text Available Background: This study aimed to examine the relationship between changes in systemic vitamin B12 concentrations with pro-inflammatory cytokines, anthropometric factors and biochemical markers of cardiometabolic risk in a Saudi population. Methods: A total of 364 subjects (224 children, age: 12.99 ± 2.73 (mean ± SD years; BMI: 20.07 ± 4.92 kg/m2 and 140 adults, age: 41.87 ± 8.82 years; BMI: 31.65 ± 5.77 kg/m2 were studied. Fasting blood, anthropometric and biochemical data were collected. Serum cytokines were quantified using multiplex assay kits and B12 concentrations were measured using immunoassay analyzer. Results: Vitamin B12 was negatively associated with TNF-α (r = −0.14, p < 0.05, insulin (r = −0.230, p < 0.01 and HOMA-IR (r = −0.252, p < 0.01 in all subjects. In children, vitamin B12 was negatively associated with serum resistin (r = −0.160, p < 0.01, insulin (r = −0.248, p < 0.01, HOMA-IR (r = −0.261, p < 0.01. In adults, vitamin B12 was negatively associated with TNF-α (r = −0.242, p < 0.01 while positively associated with resistin (r = 0.248, p < 0.01. Serum resistin was the most significant predictor for circulating vitamin B12 in all subjects (r2 = −0.17, p < 0.05 and in children (r2 = −0.167, p < 0.01 while HDL-cholesterol was the predictor of B12 in adults (r2 = −0.78, p < 0.05. Conclusions: Serum vitamin B12 concentrations were associated with pro-inflammatory cytokines and biochemical markers of cardiometabolic risks in adults. Maintaining adequate vitamin B12 concentrations may lower inflammation-induced cardiometabolic risk in the Saudi adult population.

  12. Cobalt and vitamin B12 in diets for commercial laying hens on the second cycle of production

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    RK Kato

    2003-04-01

    Full Text Available The supplementation of cobalt and vitamin B12 in diets for commercial laying hens on the second production cycle was studied. Four hundred and eighty light commercial laying hens, Lohmann LSL, were used at initial phase of forced molting laying period. The trial was conducted in a randomized design. The plots were the treatments which were constituted by combination of five cobalt levels (0.00; 0.30; 0.60; 0.90 and 1.20ppm and two vitamin B12 levels (without and with 10µ/kg, and the split-plots were four periods (21, 42, 63 and 84 days during the second period of production, with 4 repetitions and 12 hens per experimental unit. Food and water were provided ad libitum and eggs were collected twice daily. Performance and egg quality parameters were evaluated. At the end of experimental period, two layers from each treatment were slaughtered, and liver and blood samples were taken for analysis. Performance and egg quality were not different (p>0.05 among cobalt supplementation levels, although egg damage data were different (p<0.05. Supplementation with vitamin B12 decreased egg weight. No influence of cobalt or vitamin B12 supplementation was seen on the concentration of cobalt in the liver and yolk as well as on blood analysis (hematrocrit, hemoglobin, erythrocytes, and leukocytes. The results revealed that vitamin B12 supplementation was important for commercial laying hens on the second cycle of production, but not cobalt supplementation.

  13. An observational study of vitamin b12 levels and peripheral neuropathy profile in patients of diabetes mellitus on metformin therapy.

    Science.gov (United States)

    Gupta, Kamesh; Jain, Anand; Rohatgi, Anurag

    A descriptive, observational study was completed in a tertiary care hospital between November 2014 and March 2016. Fifty consecutive patients of Type 2-Diabetes Mellitus who had been on metformin therapy for at least three months were included in our study. Several Parameters were compared with vitamin B12 levels and severity of peripheral neuropathy (using Toronto Clinical Scoring System (TCSS) and Nerve Conduction Velocity). These included the duration of diabetes, duration of metformin usage, dietary history, and HbA1c levels. Definite B12 deficiency was defined as B12peripheral neuropathy (r=0.40). The mean TCSS score was 6.8. The percentage of patients with mild neuropathy was 28%, with moderate neuropathy was 20% and severe neuropathy in 12% of the patients. The average duration of metformin use in patients without peripheral neuropathy was 5.5yrs whereas the average length of metformin use in patients with peripheral neuropathy was 10.4 yrs. Patients on long-term metformin therapy are at a high risk for Vitamin B12 deficiency and peripheral neuropathy. Interval Screening for peripheral neuropathy is recommended for patients on metformin even if Vitamin B12 levels appear to be normal. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  14. Vitamin B12 deficiency in the brain leads to DNA hypomethylation in the TCblR/CD320 knockout mouse

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    Fernàndez-Roig Sílvia

    2012-05-01

    Full Text Available Abstract Background DNA methylation is an epigenetic phenomenon that can modulate gene function by up or downregulation of gene expression. Vitamin B12 and folate pathways are involved in the production of S-Adenosylmethionine, the universal methyl donor. Findings Brain vitamin B12 concentration and global DNA methylation was determined in transcobalamin receptor (TCblR/CD320 knock out (KO (n = 4 and control mice (n = 4 at 20–24 weeks of age. Median [IQR] brain vitamin B12 concentrations (pg/mg in TCblR/CD320 KO mice compared with control mice was 8.59 [0.52] vs 112.42 [33.12]; p CD320 KO compared with control mice (Median [IQR]: 0.31[0.16] % vs 0.55[0.15] %; p  Conclusions In TCblR/CD320 KO mice, brain vitamin B12 drops precipitously by as much as 90% during a 20 week period. This decrease is associated with a 40% decrease in global DNA methylation in the brain. Future research will reveal whether the disruption in gene expression profiles due to changes in DNA hypomethylation contribute to central nervous system pathologies that are frequently seen in vitamin B12 deficiency.

  15. Effect of vitamin B12 pulse addition on the performance of cobalt deprived anaerobic granular sludge bioreactors

    KAUST Repository

    Fermoso, Fernando G.

    2010-07-01

    The effect of a pulse addition of vitamin B12 as cobalt source to restore the performance of cobalt depleted methanol-fed bioreactors was investigated. One upflow anaerobic sludge bed (UASB) reactor was supplied with a pulse of vitamin B12, and its operation was compared to that of another cobalt depleted UASB reactor to which a pulse of CoCl2 was given. The addition of cobalt in the form of CoCl2 supplies enough cobalt to restore methanogenesis and maintain full methanol degradation coupled to methane production during more than 35 days after the CoCl2 pulse. Similar to CoCl2, pulse addition of vitamin B12 supplies enough cobalt to maintain full methanol degradation during more than 35 days after the pulse. However, the specific methanogenic activities (SMAs) of the sludge in the vitamin B12 supplied reactor were around 3 times higher than the SMA of the sludge from the CoCl2 supplied reactor at the same sampling times. An appropriate dosing strategy (repeated pulse dosing) combined with the choice of vitamin B12 as the cobalt species is suggested as a promising dosing strategy for methanol-fed anaerobic bioreactors limited by the micronutrient cobalt. © 2010 Elsevier Ltd. All rights reserved.

  16. EFFECTS OF RUMEN PROTECTED METHIONINE AND VITAMIN B12 ON RBC PARAMETERS OF DAIRY COWS IN EARLY LACTATION

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    Morteza Safarkhanlou

    2016-12-01

    Full Text Available To study the effects of rumen-protected methionine and vitamin B12 as well as their interactions on the parameters of red blood cells of dairy cows in early lactation, 16 Holstein cows in early lactation in experiment with randomized complete block design with the 2×2 factorial arrangement used for 42 days. In this experiment, there were four treatments, which in each treatment is placed two cows primi-parous and two cows multi-parous. Treatments included: 1 The group receiving the basal diet, 2 The group receiving the basal diet with vitamin B12 injections, 3 The group receiving the basal diet with rumen-protected methionine, 4 The group receiving the basal diet with vitamin B12 injections and rumen-protected methionine. The results showed that in the use of vitamin B12 and rumen-protected methionine, there is no significant difference between the experimental groups in the number of red blood cells, hemoglobin levels and blood hematocrit. Mean corpuscular (cell volume and mean corpuscular (cell hemoglobin did increase with vitamin B12 supplementation. In a general conclusion, it seems that increasing MCV and MCH may result in improvement in oxygenation and in turn lead to improvement on dry matter intake and milk production.

  17. Antiprothrombin Antibodies

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    Polona Žigon

    2015-05-01

    Full Text Available In patients with the antiphospholipid syndrome (APS, the presence of a group of pathogenic autoantibodies called antiphospholipid antibodies causes thrombosis and pregnancy complications. The most frequent antigenic target of antiphospholipid antibodies are phospholipid bound β2-glycoprotein 1 (β2GPI and prothrombin. The international classification criteria for APS connect the occurrence of thrombosis and/or obstetric complications together with the persistence of lupus anticoagulant, anti-cardiolipin antibodies (aCL and antibodies against β2GPI (anti-β2GPI into APS. Current trends for the diagnostic evaluation of APS patients propose determination of multiple antiphospholipid antibodies, among them also anti-prothrombin antibodies, to gain a common score which estimates the risk for thrombosis in APS patients. Antiprothrombin antibodies are common in APS patients and are sometimes the only antiphospholipid antibodies being elevated. Methods for their determination differ and have not yet been standardized. Many novel studies confirmed method using phosphatidylserine/prothrombin (aPS/PT ELISA as an antigen on solid phase encompass higher diagnostic accuracy compared to method using prothrombin alone (aPT ELISA. Our research group developed an in-house aPS/PT ELISA with increased analytical sensitivity which enables the determination of all clinically relevant antiprothrombin antibodies. aPS/PT exhibited the highest percentage of lupus anticoagulant activity compared to aCL and anti-β2GPI. aPS/PT antibodies measured with the in-house method associated with venous thrombosis and presented the strongest independent risk factor for the presence of obstetric complications among all tested antiphospholipid antibodies

  18. An antibody that prevents serpin polymerisation acts by inducing a novel allosteric behaviour.

    Science.gov (United States)

    Motamedi-Shad, Neda; Jagger, Alistair M; Liedtke, Maximilian; Faull, Sarah V; Nanda, Arjun Scott; Salvadori, Enrico; Wort, Joshua L; Kay, Christopher W M; Heyer-Chauhan, Narinder; Miranda, Elena; Perez, Juan; Ordóñez, Adriana; Haq, Imran; Irving, James A; Lomas, David A

    2016-10-01

    Serpins are important regulators of proteolytic pathways with an antiprotease activity that involves a conformational transition from a metastable to a hyperstable state. Certain mutations permit the transition to occur in the absence of a protease; when associated with an intermolecular interaction, this yields linear polymers of hyperstable serpin molecules, which accumulate at the site of synthesis. This is the basis of many pathologies termed the serpinopathies. We have previously identified a monoclonal antibody (mAb4B12) that, in single-chain form, blocks α1-antitrypsin (α1-AT) polymerisation in cells. Here, we describe the structural basis for this activity. The mAb4B12 epitope was found to encompass residues Glu32, Glu39 and His43 on helix A and Leu306 on helix I. This is not a region typically associated with the serpin mechanism of conformational change, and correspondingly the epitope was present in all tested structural forms of the protein. Antibody binding rendered β-sheet A - on the opposite face of the molecule - more liable to adopt an 'open' state, mediated by changes distal to the breach region and proximal to helix F. The allosteric propagation of induced changes through the molecule was evidenced by an increased rate of peptide incorporation and destabilisation of a preformed serpin-enzyme complex following mAb4B12 binding. These data suggest that prematurely shifting the β-sheet A equilibrium towards the 'open' state out of sequence with other changes suppresses polymer formation. This work identifies a region potentially exploitable for a rational design of ligands that is able to dynamically influence α1-AT polymerisation. © 2016 The Author(s).

  19. [Vitamin B12-independent strains of Methylophaga marina isolated from Red Sea algae].

    Science.gov (United States)

    Li, Ts D; Doronina, N V; Ivanova, E G; Trotsenko, Iu A

    2007-01-01

    Two strains (KM3 and KM5) of halophilic methylobacteria isolated from Red Sea algae do not require vitamin B12 for growth and can use methanol, methylamine, dimethylamine, trimethylamine, dimethyl sulfide, and fructose as sources of carbon and energy. The cells of these strains are gram-negative motile monotrichous (strain KM3) or peritrichous (strain KM5) rods. The strains are strictly aerobic and require Na+ ions but not growth factors for growth. They are oxidase- and catalase-positive and reduce nitrates to nitrites. Both strains can grow in a temperature range of 4 to 37 degrees C (with optimal growth at 29-34 degrees C), at pH between 5.5 and 8.5 (with optimal growth at pH 7.5-8.0), and in a range of salt concentrations between 0.5 and 15% NaCl (with optimal growth at 5-9% NaCl). The phospholipids of these strains are dominated by phosphatidylethanolamine and phosphatidylglycerol and also include phosphatidylcholine, phosphatidylserine, and cardiolipin. The dominant fatty acids are C(16:1omega7c) and C(16:0). The major ubiquinone is Q8. The cells accumulate ectoin, glutamate, and sucrose as intracellular osmoprotectants. The strains implement the 2-keto-3-deoxy-6-phosphogluconate-dependent variant of the ribulose monophosphate pathway. The G+C content of the DNA is 44.4-44.7 mol %. Analysis of the 16S rRNA genes showed that both strains belong to Gammaproteobacteria and have a high degree of homology (99.4%) to Methylophaga marina ATCC 35842T . Based on the data of polyphasic taxonomy, strains KM3 and KM5 are identified as new strains M. marina KM3 (VKM B-2386) and M. marina KM5 (VKM B-2387). The ability of these strains to produce auxins (indole-3-acetic acid) suggests their metabolic association with marine algae.

  20. Engineering a vitamin B12 high-throughput screening system by riboswitch sensor in Sinorhizobium meliloti.

    Science.gov (United States)

    Cai, Yingying; Xia, Miaomiao; Dong, Huina; Qian, Yuan; Zhang, Tongcun; Zhu, Beiwei; Wu, Jinchuan; Zhang, Dawei

    2018-05-11

    As a very important coenzyme in the cell metabolism, Vitamin B 12 (cobalamin, VB 12 ) has been widely used in food and medicine fields. The complete biosynthesis of VB 12 requires approximately 30 genes, but overexpression of these genes did not result in expected increase of VB 12 production. High-yield VB 12 -producing strains are usually obtained by mutagenesis treatments, thus developing an efficient screening approach is urgently needed. By the help of engineered strains with varied capacities of VB 12 production, a riboswitch library was constructed and screened, and the btuB element from Salmonella typhimurium was identified as the best regulatory device. A flow cytometry high-throughput screening system was developed based on the btuB riboswitch with high efficiency to identify positive mutants. Mutation of Sinorhizobium meliloti (S. meliloti) was optimized using the novel mutation technique of atmospheric and room temperature plasma (ARTP). Finally, the mutant S. meliloti MC5-2 was obtained and considered as a candidate for industrial applications. After 7 d's cultivation on a rotary shaker at 30 °C, the VB 12 titer of S. meliloti MC5-2 reached 156 ± 4.2 mg/L, which was 21.9% higher than that of the wild type strain S. meliloti 320 (128 ± 3.2 mg/L). The genome of S. meliloti MC5-2 was sequenced, and gene mutations were identified and analyzed. To our knowledge, it is the first time that a riboswitch element was used in S. meliloti. The flow cytometry high-throughput screening system was successfully developed and a high-yield VB 12 producing strain was obtained. The identified and analyzed gene mutations gave useful information for developing high-yield strains by metabolic engineering. Overall, this work provides a useful high-throughput screening method for developing high VB 12 -yield strains.

  1. COGNITIVE IMPAIRMENTS IN VITAMIN B12 AND FOLIC ACID DEFICIENCIES AND HYPERHOMOCYSTEINEMIA

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    P. R. Kamchatnov

    2015-01-01

    Full Text Available Vitamin metabolic disorders can cause diverse dysfunctions of both the peripheral and central nervous systems. There is conclusive evidence that cyanocobalamin (vitamin B12 and folic acid deficiencies may lead to diminished cognitive functions even to the extent of developing dementia. Cognitive impairments may be accompanied by involvement of other regions of the central nervous system, the corticospinal tract in particular, less frequently by brainstem and cerebellar disorders. Changes in nervous system functions in the presence of cyanocobalamin deficiency may predominate in the clinical picture, ahead of the occurrence of hematological changes. The paper considers the possible mechanisms for involvement of brain neurons in deficiency of cyanocobalamin and in that of folic acid in particular in patients with hyperhomocysteinemia. The low serum concentration of folic acid or cyanocobalamin in the elderly raises the risk of developing Alzheimer’s disease in future (by almost twice and vascular dementia. The authors give the results of randomized clinical trials evaluating the efficacy of the vitamins used in patients with cognitive impairments. Thus, there are data that the use of cyanocobalamin in patients with lacunar infarcts and moderate cognitive impairments may give rise to their complete recovery and reduce the risk of depressive disorders. Intramuscular cyanocobalamin used in a daily dose of 1000 μg for 5 days, then 1000 μg once monthly is demonstrated to be efficacious. This therapy may be effective in patients with different types of dementia and cognitive diminution, primarily in those with these conditions and its serum concentration of less 150 pmol/l. Among the side effects while taking folic acid, there may be higher incidence rates of convulsive attacks. A number of trials have shown the efficacy of cyanocobalamin, pyridoxine, and folic acid in preventing acute cerebral ischemic episodes; however, not all the investigations

  2. Anemia and hematinic deficiencies in gastric parietal cell antibody-positive and antibody-negative erosive oral lichen planus patients with thyroid antibody positivity.

    Science.gov (United States)

    Chang, Julia Y-F; Chen, I-Chang; Wang, Yi-Ping; Wu, Yu-Hsueh; Chen, Hsin-Ming; Sun, Andy

    2016-11-01

    Serum gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) are found in some erosive oral lichen planus (EOLP) patients. This study assessed whether serum GPCA, TGA and TMA and EOLP itself played significant roles in causing anemia and hematinic deficiencies in TGA/TMA-positive EOLP patients with GPCA positivity (GPCA + /TGA/TMA/EOLP patients) or negativity (GPCA - /TGA/TMA/EOLP patients). The mean corpuscular volume (MCV) and mean blood hemoglobin (Hb), iron, vitamin B12, and folic acid levels were measured and compared between any two of the four groups of 29 GPCA + /TGA/TMA/EOLP patients, 80 GPCA - /TGA/TMA/EOLP patients, 198 all antibodies-negative EOLP patients (Abs - /EOLP patients), and 218 healthy control individuals. GPCA + /TGA/TMA/EOLP patients had significantly lower mean Hb and vitamin B12 levels as well as significantly greater frequencies of Hb, iron, and vitamin B12 deficiencies than healthy controls. GPCA + /TGA/TMA/EOLP patients had significantly lower serum vitamin B12 level and higher MCV as well as a significantly greater frequency of vitamin B12 deficiency than GPCA - /TGA/TMA/EOLP patients. Furthermore, both GPCA - /TGA/TMA/EOLP and Abs - /EOLP patients did have significantly lower mean Hb, MCV, and iron (for women only) levels, as well as significantly greater frequencies of Hb and iron deficiencies than healthy controls. However, there were no significant differences in measured blood data between GPCA - /TGA/TMA/EOLP and Abs - /EOLP patients. We conclude that serum GPCA is the major factor causing vitamin B12 deficiency, macrocytosis and pernicious anemia in GPCA + /TGA/TMA/EOLP patients. ELOP itself but not TGA/TMA positivity plays a significant role in causing anemia and hematinic deficiencies in GPCA - /TGA/TMA/EOLP patients. Copyright © 2016. Published by Elsevier B.V.

  3. Electron transfer. 93. Further reactions of transition-metal-center oxidants with vitamin B12s (Cob(I)alamin)

    International Nuclear Information System (INIS)

    Pillai, G.C.; Ghosh, S.K.; Gould, E.S.

    1988-01-01

    Vitamin B 12s (cob(I)alamin) reduces europium(III), titanium(IV) (TiO(C 2 O 4 ) 2 2- ), and uranium(VI) in aqueous solution. These oxidants undergo one-electron changes, leading in each case to the cobalt product cob(II)alamin (B 12r ). The reduction of Eu 3+ , which is inhibited by TES buffer, but not by glycine, is outer sphere. Its limiting specific rate (1 x 10 2 M -1 s -1 ), incorporated in the Marcus treatment, yields a B 12s ,B 12r self-exchange rate of 10 4.8±0.5 M -1 s -1 . Reductions of TiO(C 2 O 4 ) 2 2- are accelerated by H + and by acetic acid. Kinetic patterns suggest three competing reaction paths involving varying degrees of protonation of the Ti(IV) center or its association with acetic acid. The very rapid reduction of U(VI) (k = 4 x 10 6 M -1 s -1 ) yields U(V) in several buffering media, even when B 12s is taken in excess. The much slower conversion of U(V) to U(IV), although thermodynamically favored, appears to be retarded by the extensive reorganization of the coordination sphere of oxo-bound U(V) that must accompany its acceptance of an additional electron. The observed specific rate for the B 12s -U(VI) reaction is in reasonable agreement, in the framework of the Marcus formalism, with reported values of the formal potential and the self-exchange rate for U(V,VI). 37 references, 4 tables

  4. Correlations between maternal, breast milk, and infant vitamin B12 concentrations among mother-infant dyads in Vancouver, Canada and Pry Veng, Cambodia: an exploratory analysis

    Science.gov (United States)

    Vitamin B12 plays an essential role in fetal and infant development. In regions where animal source food consumption is low and perinatal supplementation is uncommon, infants are at risk of vitamin B12 deficiency. In this secondary analysis, we measured total vitamin B12 concentrations in maternal a...

  5. Homocisteína, acido fólico y vitamina B12 en adultos mayores venezolanos

    OpenAIRE

    Meertens G, Lesbia; Díaz W, Nayka; Solano R, Liseti; Baron, Maria Adela; Rodríguez M, Adelmo

    2007-01-01

    Los cambios anatomo-fisiológicos propios del envejecimiento hacen de los adultos mayores un grupo vulnerable a los estados de malnutrición y deficiencias específicas de nutrientes como la vitamina B12 y el folato. El objetivo de este estudio fue establecer la relación existente entre la vitamina B12, folato, homocisteína y el consumo y adecuación de estos nutrientes. Se evaluaron 55 adultos mayores de 60 años de edad, de ambos sexos, no institucionalizados, a quienes se les determinó homocist...

  6. Perspectives on Peripheral Neuropathy as a Consequence of Metformin-Induced Vitamin B12 Deficiency in T2DM

    Directory of Open Access Journals (Sweden)

    Marwan A. Ahmed

    2017-01-01

    Full Text Available Peripheral neuropathy (PN is a primary complication of type 2 diabetes mellitus (T2DM and a direct manifestation of vitamin B12 deficiency. Examining the effects of metformin use on PN status became imperative following clinical studies that showed the vitamin B12-lowering effect of the medication. The complexity of the topic and the inconsistency of the results warrant consideration of topic-specific perspectives for better understanding of the available evidence and more appropriate design of future studies.

  7. Pharmacokinetics of inorganic cobalt and a vitamin B12 supplement in the Thoroughbred horse: Differentiating cobalt abuse from supplementation.

    Science.gov (United States)

    Hillyer, L L; Ridd, Z; Fenwick, S; Hincks, P; Paine, S W

    2018-05-01

    While cobalt is an essential micronutrient for vitamin B 12 synthesis in the horse, at supraphysiological concentrations, it has been shown to enhance performance in human subjects and rats, and there is evidence that its administration in high doses to horses poses a welfare threat. Animal sport regulators currently control cobalt abuse via international race day thresholds, but this work was initiated to explore means of potentially adding to application of those thresholds since cobalt may be present in physiological concentrations. To devise a scientific basis for differentiation between presence of cobalt from bona fide supplementation and cobalt doping through the use of ratios. Six Thoroughbred horses were given 10 mL vitamin B 12 /cobalt supplement (Hemo-15 ® ; Vetoquinol, Buckingham, Buckinghamshire, UK., 1.5 mg B 12 , 7 mg cobalt gluconate = 983 μg total Co) as an i.v. bolus then an i.v. infusion (15 min) of 100 mg cobalt chloride (45.39 mg Co) 6 weeks later. Pre-and post-administration plasma and urine samples were analysed for cobalt and vitamin B 12 . Urine and plasma samples were analysed for vitamin B 12 using an immunoassay and cobalt concentrations were measured via ICP-MS. Baseline concentrations of cobalt in urine and plasma for each horse were subtracted from their cobalt concentrations post-administration for the PK analysis. Compartmental analysis was used for the determination of plasma PK parameters for cobalt using commercially available software. On administration of a vitamin B 12 /cobalt supplement, the ratio of cobalt to vitamin B 12 in plasma rapidly increased to approximately 3 and then rapidly declined below a ratio of 1 and then back to near baseline over the next week. On administration of 100 mg cobalt chloride, the ratio initially exceeded 10 in plasma and then declined with the lower 95% confidence interval remaining above a ratio of 1 for 7 days. For two horses with extended sampling, the plasma ratio remained above one for

  8. Affinity for 57Co-Vitamin B12 by a wide histologic variety of tumor types in mice

    International Nuclear Information System (INIS)

    Shon, M. H.; Park, S. A.; Kim, S. H.; Jeong, K. H.; Lim, C. Y.

    1998-01-01

    The search for tumor-avid agents for use in nuclear medicine imaging is an ongoing field of importance. The purpose of this study was to determine the affinity for radiolabeled vitamin B 12 by a wide histologic variety of tumor types in mice. Seventeen different types of tumor were grown subcutaneously in female Balb/C or Balb nu/nu(nude) mice. When the tumors reached about 1 cm in diameter, mice were injected intraperitoneally with 57 Co-vitamin B 12 . Twenty-four hours later, the mice were sacrificed. Organs and tissues were removed, weighed, and activity per mg determined by gamma counter. Values represented cpm/mg tissue that was normalized to 20 grams body weight for each mouse. A wide variety of tumor types showed significant uptake and concentration of 57 Co-vitamin B 12 , as evidenced by tumor:tissue activity ratios. For many tissues of great importance in terms of background (bone, muscle, blood), the tumor:tissue activity ratios of uptake were high. These data strongly suggest that further efforts to evaluate the utility of radiolabeled adducts of vitamin B 12 for clinical use in oncologic imaging are warranted

  9. Modulation of the Antioxidant System Efficacy in Irradiated Rats Supplemented with Vitamin B12 cobalamin and Folic Acid

    International Nuclear Information System (INIS)

    Omran, M.F.; Abu-Zied, N.M.

    2006-01-01

    The present study has been performed to investigate the possible curative and protective role of supplemented vitamin B 12 and folic acid in the irradiation induced changes in certain biochemical parameters in hepatic tissue and blood. The biochemical analysis was done at one and fourteen days post irradiation. The data revealed serious effects of radiation exposure on the membrane integrity as reflected by increased serum potassium associated with decreased sodium levels. Oxidation of lipid and protein with antioxidant disorders were recorded after radiation exposure as reflected by increased contents of carbonyl and Gamma glutamyl transferase. The results showed significant increase in the level of lipid peroxide product (malonaldehyde) and significant decrease in the level of antioxidant defense system (glutathione, glutathione peroxidase, super oxid dismutase, catalase and glucose-6-phospate dehydrogenase) after one and fourteen day's supplementation with vitamin B 12 and folic acid. Supplemented of vitamin B 12 and folic acid before radiation exposure attenuated the harmful effects of irradiation on the most chosen parameters. The beneficial role of supplemented vitamin B 12 and folic acid may be related to its ability in quenching free radicals scavenging reactive oxygen species and improving regeneration in the biological tissues

  10. Nutrition Quality and Microbiology of Goat Milk Kefir Fortified with Vitamin B12 and Vitamin D3 during Storage

    Science.gov (United States)

    Dianti, EP; Anjani, G.; Afifah, DN; Rustanti, N.; Panunggal, B.

    2018-02-01

    Goat milk kefir fortified vitamin B12 and vitamin D3 can be an alternative to improve insulin resistance. Fortification of vitamin B12 and vitamin D3 could affect the balance of complex ecosystems of bacteria and yeasts in goat milk kefir. We analyzed the nutritional quality and microbiology of goat milk kefir during storage. This experiment was done with completely randomized design consisted of five treatments, ie storage day 0, 3rd, 6th, 9th, and 15th. Vitamin B12, vitamin D3, protein were analyzed using spectrophotometric, fat using babcock method, total lactic acid bacteria using total plate count, pH with pH meter, and viscosity using ostwald method. During 15 days in refrigerated storage, there was no significant difference (p>0,05) of vitamin B12 concentration, protein, fat, and viscosity of kefir. Storage time of the final product caused the decrease of vitamin D3 concentration between day 9 and 15 (p=0,038), pH (p=0,023), and total lactic acid of kefir (p=0,0001). Total lactic acid bacteria increased until 9 days of storage (6161 ± 1.296x107cfu / ml), but decreased to 24% on day 15 (150 ±7.78x107cfu/ml). pH kefir tends to fluctuate during storage with the highest pH value of 4,38 on day-3, and lowest 4.13 on day-9.

  11. Prevalence of iron, folate, and vitamin B12 deficiencies in 20 to 49 years old women: Ensanut 2012

    Directory of Open Access Journals (Sweden)

    Teresa Shamah-Levy

    2015-09-01

    Full Text Available Objective. To describe the prevalence of iron, folate, and B12 deficiencies in Mexican women of reproductive age from the National Health and Nutrition Survey (Ensanut 2012.Materials and methods. Data came from a  ationalprobabilistic survey, representative from rural and urban areas,and different age groups. Blood samples were obtained from 4 263, 20 to 49 years old women for serum ferritin, vitamin B12 and serum folate oncentrations. The prevalence of deficiencies, was assessed using adjusted logistic regression models. Results. The deficiency of folate was 1.9% (95%CI1.3-2.8, B12 deficiency was 8.5% (95%CI 6.7-10.1 and iron deficiency was 29.4% (95%CI 26.5-32.2. No differences were found when compared with 2006, 24.8% (95%CI 22.3-27.2.Conclusions. The vitamin B12 deficiency is still a problem for women of reproductive age and their offspring in Mexico,while folate deficiency disappeared as a problem. Iron deficiency needs prevention and fortification strategies.

  12. Prevalence of iron, folate, and vitamin B12 deficiencies in 20 to 49 years old women: Ensanut 2012.

    Science.gov (United States)

    Shamah-Levy, Teresa; Villalpando, Salvador; Mejía-Rodríguez, Fabiola; Cuevas-Nasu, Lucía; Gaona-Pineda, Elsa Berenice; Rangel-Baltazar, Eduardo; Zambrano-Mujica, Norma

    2015-01-01

    To describe the prevalence of iron, folate, and B12 deficiencies in Mexican women of reproductive age from the National Health and Nutrition Survey (Ensanut) 2012. Data came from a national probabilistic survey, representative from rural and urban areas, and different age groups. Blood samples were obtained from 4 263, 20 to 49 years old women for serum ferritin, vitamin B12 and serum folate concentrations. The prevalence of deficiencies, was assessed using adjusted logistic regression models. The deficiency of folate was 1.9% (95%CI 1.3-2.8), B12 deficiency was 8.5% (95%CI 6.7-10.1) and iron deficiency was 29.4% (95%CI 26.5-32.2). No differences were found when compared with 2006, 24.8% (95%CI 22.3-27.2). The vitamin B12 deficiency is still a problem for women of reproductive age and their offspring in Mexico, while folate deficiency disappeared as a problem. Iron deficiency needs prevention and fortification strategies.

  13. Protective efficacy of folic acid and vitamin B12 against nicotine-induced toxicity in pancreatic islets of the rat

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    Bhattacharjee Ankita

    2015-06-01

    Full Text Available Although cigarette smoking is associated with insulin resistance and an increased risk for type 2 diabetes, few studies have examined the effect of nicotine on the adult endocrine pancreas. In this study, male Wister rats were treated with nicotine (3 mg/kg body weight/day with or without supplementation of folic acid (36 μg/kg body weight/day or vitamin B12 (0.63 μg/kg body weight/day alone or in combination. Fasting blood glucose, insulin and HBA1C level and different oxidative and anti-oxidative stress parameters were measured and pancreatic tissue sections were stained with eosin-haematoxylene. Data were analysed by nonparametric statistics. The results revealed that nicotine induced prediabetes condition with subsequent damage to pancreatic islets in rats. Nicotine also caused oxidative stress in pancreatic tissue as evidenced by increased nitric oxide and malondialdehyde level and decreased superoxide dismutase, catalase and reduced glutathione level. Compared to vitamin B12 supplementation, folic acid blunted the nicotine-induced toxicity in pancreatic islets with higher efficacy. Further, folic acid and vitamin B12 in combination were able to confer significant protection on pancreatic islets against nicotine induced toxicity. These results suggest that supplementation of folic acid and vitamin B12 in combination may be a possible strategy of detoxification against nicotine-induced toxicity in pancreatic islets of the rat.

  14. Explaining the variability in recommended intakes of folate, vitamin B12, iron and zinc for adults and elderly people

    NARCIS (Netherlands)

    Doets, E.L.; Cavelaars, A.J.E.M.; Dhonukshe-Rutten, R.A.M.; Veer, van 't P.; Groot, de C.P.G.M.

    2012-01-01

    Objective To signal key issues for harmonising approaches for establishing micronutrient recommendations by explaining observed variation in recommended intakes of folate, vitamin B12, Fe and Zn for adults and elderly people. Design We explored differences in recommended intakes of folate, vitamin

  15. Elevated plasma vitamin B12 levels and risk of venous thromboembolism among cancer patients: A population-based cohort study

    DEFF Research Database (Denmark)

    Arendt, Johan Frederik Håkonsen; Farkas, Dora Kormendine; Pedersen, Lars

    2017-01-01

    INTRODUCTION: Both venous thromboembolism (VTE) and high plasma vitamin B12 levels (cobalamin, Cbl) are markers of occult cancer and aggressive cancer with a poor prognosis. In this population-based cohort study, we assessed VTE risk among cancer patients with high plasma Cbl levels. MATERIALS...

  16. Identification of structural markers for vitamin B12 and other corrinoid derivatives in solution using FTIR spectroscopy

    International Nuclear Information System (INIS)

    Taraszka, K.S.; Chen, Eefei; Metzger, T.; Chance, M.R.

    1991-01-01

    The identification of structural markers for B 12 /protein interactions is crucial to a complete understanding of vitamin B 12 transport and metabolic reaction mechanisms of B 12 coenzymes. Fourier transform infrared spectroscopy can provide direct measurements of changes in the side chains and corrin ring resulting from B 12 /protein interactions. Using FTIR spectroscopy in various solvent systems, the authors have identified structural markers for corrinoids in the physiological state. They assign the major band (denoted B), which occurs at ca. 1,630 cm -1 in D 2 O and ca. 1675 cm -1 in ethanol, to the amide I C double-bond stretching mode of the propionamide side chains of the corrin ring. The lower frequency of band B in D 2 O versus ethanol is due to the greater hydrogen-bonding properties of D 2 O that stabilize the charged amide resonance form. Since the propionamides are known to be important in protein binding, band B is a suitable marker for monitoring the interaction of these side chains with proteins. They assign bands at ca. 1,575 and 1,545 cm -1 (denoted C and D) as breathing modes of the corrin ring on the basis of the bands' solvent independence and their sensitivity to changes in axial ligation

  17. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study

    OpenAIRE

    Aroda, Vanita R.; Edelstein, Sharon L.; Goldberg, Ronald B.; Knowler, William C.; Marcovina, Santica M.; Orchard, Trevor J.; Bray, George A.; Schade, David S.; Temprosa, Marinella G.; White, Neil H.; Crandall, Jill P.

    2016-01-01

    Participants from DPP/DPPOS were assigned to placebo (n=1082) or metformin (n=1073) for 3.2 years, followed by metformin in the metformin group for 9 years. Metformin use was associated with increased risk of vitamin B12 deficiency.

  18. Vitamin B12 deficiency in diabetic subjects taking metformin: A cross sectional study in a Lebanese cohort

    Directory of Open Access Journals (Sweden)

    Joyce Zalaket

    2018-03-01

    Based on our results, we strongly recommend the routine screening of subjects with T2D on metformin for vitamin B12 deficiency due to its high prevalence and the significant clinical effects it may result in. Furthermore, we recommend, based on our data, to start treating those subjects once a borderline or low level is detected.

  19. Vitamin B12 and iron in the plasma of hamster infected with the intestinal parasite Prohemistomum vivax

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    Nemat M. El-Kewaisny

    2012-03-01

    The results showed no significant change in the level of vitamin B12, whereas, a significant decrease was observed in the level of iron (P < 0.01 in the plasma of the infected animals compared with the control group. This result suggested that a malabsorption condition occurred probably due to complex interactions between host and the used parasite (trematode.

  20. Five year changes in mental health and associations with vitamin B12/folate status of elderly Europeans

    NARCIS (Netherlands)

    Eussen, S.J.P.M.; Ferry, M.; Haller, J.; Matthys, C.; Dirren, H.

    2002-01-01

    OBJECTIVE: To describe 5-year changes of mental health in SENECA participants, and to examine whether mental health is associated with the status of vitamin B12 and folate. DESIGN: A longitudinal, multicentre study including a Baseline study, a Follow-up study, and a Finale study. SUBJECTS:

  1. Vitamin B12 Deficiency and the Role of Gender: A Cross-Sectional Study of a Large Cohort.

    Science.gov (United States)

    Margalit, Ili; Cohen, Eytan; Goldberg, Elad; Krause, Ilan

    2018-01-01

    Vitamin B12 deficiency is associated with hematological, neurological, and cardiovascular consequences. Epidemiologic data on these related illnesses indicate gender differences. A cross-sectional study was designed to examine gender differences in vitamin B12 deficiency among a healthy population. Data from healthy individuals aged 18-65, who were provided with a routine medical evaluation during 2000-2014, were retrieved from the medical charts. Individuals with background illnesses and those who had used medications or nutritional supplements were excluded. Vitamin B12 deficiency was defined by 2 cutoff values (206 and 140 pmol/L). The multivariate analysis was adjusted for age, body mass index, estimated glomerular filtration rate, hyperhomocysteinemia, folate deficiency, albumin, and transferrin saturation. Sensitivity analyses were implemented by excluding individuals with anemia, hyperhomocysteinemia, or folate deficiency and by age stratification. In all, 7,963 individuals met the inclusion criteria. Serum vitamin B12 mean levels were 312.36 and 284.31 pmol/L for women and men respectively (p variations are therefore hypothesized to play a role. © 2018 S. Karger AG, Basel.

  2. The effect of vitamin B12 and folic acid supplementation on routine haematological parameters in older people

    NARCIS (Netherlands)

    Smelt, Antonia F.H.; Gussekloo, Jacobijn; Bermingham, Lynette W.; Allen, Elizabeth; Dangour, Alan D.; Eussen, Simone J.P.M.; Favrat, Bernard; Groot, de Lisette C.P.G.M.; Kok, Frans J.; Kwok, Timothy; Mangoni, Arduino A.; Ntaios, George; Rest, van de Ondine; Seal, Eric; Vaucher, Paul; Verhoef, Petra; Stijnen, Theo; Elzen, Den Wendy P.J.

    2018-01-01

    Background/objectives: Low vitamin B12 and folate levels in community-dwelling older people are usually corrected with supplements. However, the effect of this supplementation on haematological parameters in older persons is not known. Therefore, we executed a systematic review and individual

  3. The Mitochondrion-Located Protein OsB12D1 Enhances Flooding Tolerance during Seed Germination and Early Seedling Growth in Rice

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    Dongli He

    2014-07-01

    Full Text Available B12D belongs to a function unknown subgroup of the Balem (Barley aleurone and embryo proteins. In our previous work on rice seed germination, we identified a B12D-like protein encoded by LOC_Os7g41350 (named OsB12D1. OsB12D1 pertains to an ancient protein family with an amino acid sequence highly conserved from moss to angiosperms. Among the six OsB12Ds, OsB12D1 is one of the major transcripts and is primarily expressed in germinating seed and root. Bioinformatics analyses indicated that OsB12D1 is an anoxic or submergence resistance-related gene. RT-PCR results showed OsB12D1 is induced remarkably in the coleoptiles or roots by flooding during seed germination and early seedling growth. The OsB12D1-overexpressed rice seeds could protrude radicles in 8 cm deep water, further exhibiting significant flooding tolerance compared to the wild type. Moreover, this tolerance was not affected by the gibberellin biosynthesis inhibitor paclobutrazol. OsB12D1 was identified in the mitochondrion by subcellular localization analysis and possibly enhances electron transport through mediating Fe and oxygen availability under flooded conditions. This work indicated that OsB12D1 is a promising gene that can help to enhance rice seedling establishment in farming practices, especially for direct seeding.

  4. Mood disorder with mixed, psychotic features due to vitamin b12 deficiency in an adolescent: case report

    Directory of Open Access Journals (Sweden)

    Tufan Ali

    2012-06-01

    Full Text Available Abstract Vitamin B12 is one of the essential vitamins affecting various systems of the body. Reports of psychiatric disorders due to its deficiency mostly focus on middle aged and elderly patients. Here we report a case of vitamin B 12 deficiency in a 16-year old, male adolescent who presented with mixed mood disorder symptoms with psychotic features. Chief complaints were “irritability, regressive behavior, apathy, crying and truancy” which lasted for a year. Premorbid personality was unremarkable with no substance use/exposure or infections. No stressors were present. The patient was not vegetarian. Past medical history and family history was normal. Neurological examination revealed glossitis, ataxia, rigidity in both shoulders, cog-wheel rigidity in the left elbow, bilateral problems of coordination in cerebellar examination, reduced swinging of the arms and masked face. Romberg’s sign was present. Laboratory evaluations were normal. Endoscopy and biopsy revealed atrophy of the gastric mucosa with Helicobacter Pylori colonization. Schilling test was suggestive of malabsorbtion. He was diagnosed with Mood disorder with Mixed, Psychotic Features due to Vitamin B12 Deficiency and risperidone 0.5 mg/day and intramuscular vitamin B12 500 mcg/day were started along with referral for treatment of Helicobacter pylori. A visit on the second week revealed no psychotic features. Romberg’s sign was negative and cerebellar tests were normal. Extrapyramidal symptoms were reduced while Vitamin B12 levels were elevated. Risperidone was stopped and parenteral Vitamin B12 treatment was continued with monthly injections for 3 months. Follow-up endoscopy and biopsy at the first month demonstrated eradication of H. pylori. He was followed monthly for another 6 months and psychiatric symptoms did not recur at the time of last evaluation. Despite limitations, this case may underline the observation that mood disorders with psychotic features

  5. Comparison of virulence of Francisella tularensis ssp. holarctica genotypes B.12 and B.FTNF002-00.

    Science.gov (United States)

    Kreizinger, Zsuzsa; Erdélyi, Károly; Felde, Orsolya; Fabbi, Massimo; Sulyok, Kinga M; Magyar, Tibor; Gyuranecz, Miklós

    2017-02-10

    Two main genetic groups (B.12 and B.FTNF002-00) of Francisella tularensis ssp. holarctica are endemic in Europe. The B.FTNF002-00 group proved to be dominant in Western European countries, while strains of the B.12 group were isolated mainly in Northern, Central and Eastern Europe. The clinical course of tularemia in the European brown hare (Lepus europaeus) also shows distinct patterns according to the geographical area. Acute course of the disease is observed in hares in Western European countries, while signs of sub-acute or chronic infection are more frequently detected in the eastern part of the continent. The aim of the present study was to examine whether there is any difference in the virulence of the strains belonging to the B.FTNF002-00 and B.12 genetic clades. Experimental infection of Fischer 344 rats was performed by intra-peritoneal injection of three dilutions of a Hungarian (B.12 genotype) and an Italian (B.FTNF002-00 genotype) F. tularensis ssp. holarctica strain. Moderate difference was observed in the virulence of the two genotypes. Significant differences were observed in total weight loss values and scores of clinical signs between the two genotypes with more rats succumbing to tularemia in groups infected with the B.FTNF002-00 genotype. Results of the experimental infection are consistent with previous clinical observations and pathological studies suggesting that F. tularensis ssp. holarctica genotype B.FTNF002-00 has higher pathogenic potential than the B.12 genotype.

  6. Monoclonal antibody

    International Nuclear Information System (INIS)

    Oyamada, Hiyoshimaru

    1987-01-01

    Some aspects of monoclonal antibodies are described, centering on studies made by the author and those presented at the Second International Conference on Monoclonal Antibody Immunoconjugates for Cancer held in March this year (1987). The history of immuno-nuclear medicine and procedures for producing monoclonal antibodies are briefly outlined. Monoclonal antibodies are immunoglobulins. Here, the structure of IgG, which is used most frequently, is described. An IgG is composed of two antigen binding fragments (Fab) and one crystallizable fragment (Fc). The end portion of a Fab reacts with an antigen. One of the major applications of immuno-nuclear medicine is the diagnosis of cancer. As label nucleides, 131 I and 111 I were selected in most cases in the past while 123 I and 99m Tc are currently used more often. Advantages and disadvantages of this diagnosis method is discussed citing studies presented at the First (1986) and Second (1987) International Conference on Monoclonal Antibody Immunoconjugates for Cancer. The present status of the application of monoclonal antibodies to treatment of cancer is also described. (Nogami, K.)

  7. Photoluminescence Investigation of the Indirect Band Gap and Shallow Impurities in Icosahedral B12As2

    Science.gov (United States)

    2012-07-05

    semiconductor that exhibits unusual properties as the result of the bonding within the 12-atom boron icosahe- dron that is an integral part of its crystal...on interstitial sites of the boron icosahe- dron . Ni doping has produced n-type material (via a Ni interstitial) in other compounds incorporating boron

  8. Stability of Benzotriazole Derivatives with Free Cu, Zn, Co and Metal-Containing Enzymes: Binding and Interaction of Methylbenzotriazoles with Superoxide Dismutase and Vitamin B12

    Science.gov (United States)

    Abudalo, R. A.; AbuDalo, M. A.; Hernandez, M. T.

    2018-02-01

    Benzotriazole derivatives form very strong bonds with transition metals, and are the most widely used type of industrial corrosion inhibitor. Some benzotriazole derivatives have been implicated as hormone regulators which also carry the ability to induce uncoupling responses or otherwise inhibit respiration processes in some microorganisms. However, the mechanisms associated with benzotriazole toxicity and inhibition are unknown. Using Differential Pulse Polarography, the stability constants of commercially significant corrosion inhibitors, 4-and 5-methylbenzotriazole, coordinated with free Cu (II) and Co (III), were determined to be 1015 and 108, respectively. Polarographic analyses were extended to confirm that methylbenzotriazole also binds the copper center(s) in the ubiquitous enzyme superoxide dismutase, and the Corrin site in the coenzyme cobalamin (vitamin B12). These results suggest that the metal-chelating ability of this unique class of compounds may confer inhibition to certain enzyme systems.

  9. Study of the Mn-binding sites in photosystem II using antibodies raised against lumenal regions of the D1 and D2 reaction center proteins

    Energy Technology Data Exchange (ETDEWEB)

    Dalmasso, Enrique Agustin [Univ. of California, Berkeley, CA (United States)

    1992-04-01

    The experiments discussed in this thesis focus on identifying the protein segments or specific amino acids which provide ligands to the Mn cluster of photosystem II (PS II). This Mn cluster plays a central role in the oxygen-evolving complex (OEC) of PS II. The Mn cluster is thought to be bound by lumenal regions of the PS II reaction center proteins known as D1 and D2. First, several peptides were synthesized which correspond to specific lumenal segments of the D1 and D2 proteins. Next, polyclonal antibodies were successfully elicited using three of these peptides. The peptides recognized by these antibodies correspond to protein segments of the spinach reaction center proteins: Ile-321 to Ala-344 of D1 (D1-a), Asp-319 to Arg-334 of D1 (D1-b), and Val-300 to Asn-319 of D2 (D2-a). These antibodies were then used in assays which were developed to structurally or functionally probe the potential Mn-binding regions of the D1 and D2 proteins.

  10. Importância da vitamina B12 na avaliação clínica do paciente idoso = Importance of vitamin B12 screening in clinical evaluation of elderly patient

    Directory of Open Access Journals (Sweden)

    Futterleib, Alexandre

    2005-01-01

    Conclusão: A investigação da deficiência de vitamina B12 é um procedimento importante na avaliação clínica do paciente idoso, já que o diagnóstico precoce pode evitar distúrbios neurológicos e hematológicos, bem como proporcionar melhor qualidade de vida ao paciente

  11. SERUM VITAMIN B12, IRON AND FOLIC ACID DEFICIENCIES IN OBESE INDIVIDUALS SUBMITTED TO DIFFERENT BARIATRIC TECHNIQUES.

    Science.gov (United States)

    Silva, Rafaella de Andrade; Malta, Flávia Monteiro França; Correia, Maria Flora Ferreira Sampaio Carvalho; Burgos, Maria Goretti Pessoa de Araújo

    Different surgical techniques to combat obesity combine malabsorption with restrictive procedures and can lead to metabolic problems, such as micronutrient deficiencies. Assess vitamin B12, iron and folic acid deficiencies associated with the lifestyle of obese individuals having been submitted to different bariatric techniques. A retrospective analysis was performed using the electronic charts of patients submitted to bariatric surgery involving adjustable gastric banding and Roux-en-Y gastric bypass at the São João Hospital Center in the city of Porto, Portugal, between 2005 and 2010. The following data were collected: surgical technique, sex, age, marital status, serum concentrations of vitamin B12, iron and folic acid and postoperative lifestyle. A 5% significance level was used for the statistical analysis (pmicronutrientes. Avaliar a deficiência de vitamina B12, ferro e ácido fólico e fatores associados ao estilo de vida de obesos submetidos a diferentes técnicas cirúrgicas. Análise retrospectiva dos prontuários eletrônicos de pacientes submetidos à cirurgia bariátrica pelas técnicas de banda gástrica ajustável e bypass gástrico em Y-de-Roux, no Centro Hospitalar de São João, E.P.E., Porto - Portugal, no período de 2005-2010. Foram coletadas: técnica cirúrgica, sexo, idade, estado civil, concentrações séricas de vitamina B12, ferro e ácido fólico e o estilo de vida no pós-operatório. Para análise estatística foi utilizado nível de significância de 5% (pmicronutrientes foram detectadas após o bypass gástrico. A deficiência de micronutriente mais prevalente foi a de ferro (21,3%), seguida da vitamina B12 (16,9%) e do ácido fólico (4,5%). A ingestão de bebida alcoólica de leve-moderada, a adesão à dieta e o uso de polivitamínicos reduziu a frequência, mas não evitou a carência de micronutrientes. A deficiência de vitamina B12, ferro e ácido fólico foi observada durante o primeiro e o segundo anos após as duas t

  12. Efeito da corticotropina sobre a absorção de vitamina B12 na mielose funicular

    Directory of Open Access Journals (Sweden)

    Horacio M. Canelas

    1965-06-01

    Full Text Available Foi estudada a absorção de vitamina B12 em 9 casos de mielose funicular antes e após a administração de ACTH por via intravenosa em um esquema terapêutico com duração variável entre 19 e 43 dias. Em 7 casos foi verificado aumento da absorção. A diferença média de modificação no teste de excreção urinaria de vitamina B12 radioativa situou-se próximo do nível de significancia estatística. Este resultado reforça a indicação do emprego de corticotropina na mielose funicular, pois o hormônio irá atuar tanto sobre o componente alérgico do prccesso desmielinizante, quanto sobre a carência de vitamina B12 resultante do déficit de absorção. Embora o material aqui analisado seja muito pequeno para garantir uma conclusão definitiva, nossos resultados demonstram que, provavelmente, o ACTH age sobre a absorção da vitamina B12 através da mucosa intestinal, e não mediante o aumento de secreção do fator intrínseco ou a mobilização dos depósitos dessa vitamina. In order to study a possible mobilizing effect of ACTH on the radioactive vitamin B12 stores, the intervals between the last urinary excretion test and the test after completion of treatment were analyzed (Table 1. It is easily noticed that in the 7 cases with increase of vitamin B12 absorption these periods were the most varied, lasting from 9 to 62 days. And also in the 2 cases with decrease of absorption the intervals were very dissimilar, namely 15 and 56 days. So, it seems that this effect of ACTH did not play a significant role in the results. Likewise, the time elapsed between the completion of treatment and the repetition of the Schilling's test had no apparent relationship with the results.

  13. The effect of folate and vitamin B12 supplementation on homocysteine concentrations: a study in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Azadibakhsh N.

    2007-10-01

    Full Text Available Background: Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. The frequency of hyperhomocysteinemia is higher in hemodialysis (HD patients than the general population. The objective of this study is to assess the efficacy of high-dose folic acid supplementation with and without vitamin B12 on lowering plasma total homocysteine (tHcy concentrations in HD patients. Methods: Thirty-six HD patients at Imam Hossein Hospital, Tehran, Iran, who had been given folic acid supplements (5 mg/d for at least 3 months before, were enrolled in this clinical trial. Subjects were also checked for other inclusion and exclusion criteria. The subjects were divided randomly into four groups and underwent two months of supplementation as follows: 5 mg/d oral folic acid + placebo in group one, 5 mg/d oral folic acid + vitamin B12 (1 mg/d orally in group two, 15 mg/d oral folic acid + placebo in group three and 15 mg/d oral folic acid + vitamin B12 (1 mg/d orally in group four. Concentrations of plasma tHcy and serum folic acid and vitamin B12 were measured at baseline and after the supplementation period. Dietary intake of patients was also determined during the supplementation period.Results: Of the folic acid supplemented patients, 27.8% had normal levels of tHcy at baseline and 72.2% had hyperhomocysteinemia. After the supplementation period, plasma tHcy increased by 1.35% in group one and decreased by 6.99%, 14.54% and 30.09% in groups two, three and four respectively. Changes in plasma tHcy and serum vitamin B12 were only significant in group four; however, no significant changes were seen for serum folic acid. The percentage of subjects reaching normal levels of plasma tHcy was 5.6 fold higher in group four than in the reference group. Conclusions: Supplementation with 15 mg/d folic acid together with 1 mg/d oral vitamin B12 is more effective in reducing tHcy levels in HD patients.

  14. Effects of supplementary folic acid and vitamin B(12) on hepatic metabolism of dairy cows according to methionine supply.

    Science.gov (United States)

    Preynat, A; Lapierre, H; Thivierge, M C; Palin, M F; Cardinault, N; Matte, J J; Desrochers, A; Girard, C L

    2010-05-01

    The present experiment was undertaken to study the interactions between dietary supplements of rumen-protected methionine (RPM) and intramuscular injections of folic acid and vitamin B(12), given from 3 wk before calving to 16 wk of lactation, on hepatic metabolism of lactating dairy cows. Sixty multiparous Holstein cows were assigned to 10 blocks of 6 cows each according to their previous milk production. Within each block, 3 cows were fed a diet calculated to supply Met as 1.83% of metabolizable protein, whereas the 3 other cows were fed the same diet supplemented with 18g of RPM calculated to provide Met as 2.23% of metabolizable protein. Within each level of Met, the cows received no vitamin supplement or weekly intramuscular injections of 160mg of folic acid alone or combined with 10mg of vitamin B(12). Liver biopsies were taken at 2, 4, 8, and 16 wk of lactation. Liver concentrations of folates and vitamin B(12) were increased by their respective supplements but this response to vitamin supplements was altered by methionine supply. Concentrations of total lipids and triglycerides increased in livers of cows fed RPM, whereas concentrations of cholesterol ester, cholesterol, diglycerides, phosphatidylethanolamine, and phosphatidylcholine were not affected. Folic acid, alone or combined with vitamin B(12), tended to increase the ratio of phosphatidylcholine to phosphatidylethanolamine. Gene expression of 5,10-methylene-tetrahydrofolate reductase, microsomal transfer protein, and phosphatidylethanolamine methyltransferase were higher in liver of cows fed RPM supplements. The relative mRNA abundance of 5,10-methylene-tetrahydrofolate reductase and methylmalonyl-CoA mutase were increased by the combined injections of folic acid and vitamin B(12), whereas those of methionine synthase and methionine synthase reductase were not affected by treatments. These results suggest that increasing supply of methyl groups, as preformed labile methyl groups or through

  15. Severe vitamin B12 deficiency in a 15-year-old boy: presentation with haemolysis and pancytopenia

    Science.gov (United States)

    Keskin, Ebru Yılmaz; Keskin, Mahmut

    2015-01-01

    A 15-year-old boy on a vegetarian diet presented with severe macrocytic anaemia (haemoglobin, 5.1 g/dL; mean corpuscular volume, 116 fL) in addition to leucopenia and thrombocytopaenia (pancytopenia), icterus secondary to haemolysis and splenomegaly. Laboratory investigations revealed severe vitamin B12 (cobalamin) deficiency. Following cobalamin replacement therapy, the patient reported increased well-being, including appetite and weight gain, and his icterus resolved. In the follow-up laboratory examinations, leucocyte and platelet counts in addition to serum bilirubin and lactate dehydrogenase levels normalised. At the end of 2 months, laboratory findings, including haemoglobin level, were all within the normal range. We present this case as a reminder that severe vitamin B12 deficiency may present with findings mimicking acute leukaemia (pancytopenia and splenomegaly) and findings suggestive of pseudothrombotic microangiopathy. PMID:25976204

  16. EVIDENCE-BASED DATA ON EFFECTIVENESS OF LACTOBACILLUS RHAMNOSUS GG AND BIFIDOBACTERIUM LACTIS ВB-12 IN PEDIATRIC PRACTICE

    Directory of Open Access Journals (Sweden)

    I. V. Andreyeva

    2011-01-01

    Full Text Available Prophylactic and therapeutic administration of prebiotics in treatment of different disorders is used very often nowadays. However, this kind of a treatment confirmed its efficacy in only several diseases. The review presents the data on efficacy of two probiotic microorganisms (L. rhamnosus GG and B. lactis Вb-12 in pediatric practice. Author summarizes and analyzes existing evidence-based data on efficacy of probiotics in treatment of acute diarrhea, prophylaxis of antibiotic-associated diarrhea and nosocomial infections. L. rhamnosus GG and B. lactis Вb-12 have their own place in prophylaxis of infections of airways and gastrointestinal tract. Administration of probiotics for treatment and prophylaxis of allergic and other diseases is reviewed. Safety of probiotics is described as well.

  17. Déficit de vitamina B12 asociado con altas dosis de metformina en adultos mayores diabéticos

    OpenAIRE

    Hugo Sánchez; Dominique Masferrer; Lydia Lera; Estrella Arancibia; Bárbara Ángel; Cecilia Albala

    2014-01-01

    Introducción: El objetivo del estudio es estimar si el déficit de B12 se asocia con el uso de la metformina en adultos mayores (AM) diabéticos. Métodos: Estudio de casos y controles en AM diabéticos. Los casos (n = 137) se definieron como AM con B12 221 pmol/L. Se definieron 4 categorías de uso de metformina: no usuarios, ≤ 850 mg/día; > 850 y < 2.550 mg/día; ≥ 2.550 mg/día. Se consideró altas dosis de metformina (≥ 2.550 mg/día). Se cal...

  18. Cobalt-vitamin B12 deficiency and the activity of methylmalonyl CoA mutase and methionine synthase in cattle.

    Science.gov (United States)

    Kennedy, D G; Young, P B; Kennedy, S; Scott, J M; Molloy, A M; Weir, D G; Price, J

    1995-01-01

    Cobalt deficiency was induced in cattle by feeding two groups of animals either a basal diet that was very low in Co (12.9-17.6 micrograms Co per kg), or the same diet supplemented with cobalt, for a total of 64 weeks. Vitamin B12 deficiency was induced, as judged by hepatic concentrations of vitamin B12 and plasma concentrations of MMA. However, the activity of holo-methylmalonyl CoA mutase was significantly reduced only in brain. This was reflected in very minor alterations in the tissue concentrations of branched chain- and odd numbered-fatty acids. The activity of holo-methionine synthase was significantly reduced in liver and brain, but there were no consequent alterations in the concentrations of phosphatidyl choline and phosphatidyl ethanolamine. This study confirms that cattle are less susceptible to the effects of cobalt deficiency than sheep, and concludes that prolonged cobalt deficiency had little significant effect on tissue metabolism.

  19. Sub-optimal vitamin B-12 levels among ART-naive HIV-positive individuals in an urban cohort in Uganda.

    Directory of Open Access Journals (Sweden)

    Aggrey S Semeere

    Full Text Available Malnutrition is common among HIV-infected individuals and is often accompanied by low serum levels of micronutrients. Vitamin B-12 deficiency has been associated with various factors including faster HIV disease progression and CD4 depletion in resource-rich settings. To describe prevalence and factors associated with sub-optimal vitamin B-12 levels among HIV-infected antiretroviral therapy (ART naïve adults in a resource-poor setting, we performed a cross-sectional study with a retrospective chart review among individuals attending either the Mulago-Mbarara teaching hospitals' Joint AIDS Program (MJAP or the Infectious Diseases Institute (IDI clinics, in Kampala, Uganda. Logistic regression was used to determine factors associated with sub-optimal vitamin B-12. The mean vitamin B-12 level was 384 pg/ml, normal range (200-900. Sub-optimal vitamin B-12 levels (<300 pg/ml were found in 75/204 (36.8%. Twenty-one of 204 (10.3% had vitamin B-12 deficiency (<200 pg/ml while 54/204 (26.5% had marginal depletion (200-300 pg/ml. Irritable mood was observed more among individuals with sub-optimal vitamin B-12 levels (OR 2.5, 95% CI; 1.1-5.6, P=0.03. Increasing MCV was associated with decreasing serum B-12 category; 86.9 fl (± 5.1 vs. 83 fl (± 8.4 vs. 82 fl (± 8.4 for B-12 deficiency, marginal and normal B-12 categories respectively (test for trend, P=0.017. Compared to normal B-12, individuals with vitamin B-12 deficiency had a longer known duration of HIV infection: 42.2 months (± 27.1 vs. 29.4 months (± 23.8; P=0.02. Participants eligible for ART (CD4<350 cells/µl with sub-optimal B-12 had a higher mean rate of CD4 decline compared to counterparts with normal B-12; 118 (± 145 vs. 22 (± 115 cells/µl/year, P=0.01 respectively. The prevalence of a sub-optimal vitamin B-12 was high in this HIV-infected, ART-naïve adult clinic population in urban Uganda. We recommend prospective studies to further clarify the causal relationships of sub

  20. Acupuncture and vitamin B12 injection for Bell′s palsy: no high-quality evidence exists

    Directory of Open Access Journals (Sweden)

    Li-li Wang

    2015-01-01

    MAIN OUTCOME MEASURES: Incomplete recovery rates were chosen as the primary outcome. RESULTS: Five studies involving 344 patients were included in the final analysis. Results showed that the incomplete recovery rate of Bell′s palsy patients was 44.50% in the acupuncture combined with vitamin B 12 group but 62.57% in the acupuncture alone group. The major acupoints were Taiyang (EX-HN5, Jiache (ST6, Dicang (ST4 and Sibai (ST2. The combined effect size showed that acupuncture combined with vitamin B 12 was better than acupuncture alone for the treatment of Bell′s palsy (RR = 0.71, 95%CI: 0.58-0.87; P = 0.001, this result held true when 8 patients lost to follow up in one study were included into the analyses (RR = 0.70, 95%CI: 0.58-0.86; P = 0.0005. In the subgroup analyses, the therapeutic effect in patients of the electroacupuncture subgroup was better than in the non-electroacupuncture subgroup (P = 0.024. There was no significant difference in the incomplete recovery rate by subgroup analysis on drug types and treatment period. Most of the included studies were moderate or low quality, and bias existed. CONCLUSION: In patients with Bell′s palsy, acupuncture combined with vitamin B 12 can reduce the risk of incomplete recovery compared with acupuncture alone in our meta-analysis. Because of study bias and methodological limitations, this conclusion is uncertain and the clinical application of acupuncture combined with vitamin B 12 requires further exploration.

  1. Homocysteine and vitamin B 12 status and iron deficiency anemia in female university students from Gaza Strip, Palestine

    Directory of Open Access Journals (Sweden)

    Mahmoud Mohammed Sirdah

    2014-06-01

    Full Text Available OBJECTIVE: Nutritional deficiencies are very significant to the overall health of humans at all ages and for both genders, yet in infants, children and women of childbearing age these deficiencies can seriously affect growth and development. The present work is aimed to assess homocysteine and vitamin B12 status in females with iron deficiency anemia from the Gaza Strip.METHODS: Venous blood samples were randomly collected from 240 female university students (18-22 years old and parameters of the complete blood count, serum ferritin, homocysteine and vitamin B12 were measured. Statistical analysis included the t-test and analysis of variance (ANOVA using the IBM SPSS software (version 18. Statistical significance was set for p-values <0.05.RESULTS: The results revealed that 20.4% of the students have iron deficiency anemia. The mean serum vitamin B12 level in females with iron deficiency anemia (212.9 ± 62.8 pg/mL was significantly lower than in normal controls (286.9 ± 57.1 pg/mL and subjects with microcytic anemia and normal ferritin (256.7 ± 71.1 pg/mL. Significantly higher serum homocysteine levels were reported in the iron deficiency anemia group (27.0 ± 4.6 µmol/L compared to normal controls (15.5 ± 2.9 µmol/L and in subjects with microcytic anemia and normal ferritin (18.1 ± 2.7 µmol/L. Statistically significant negative correlations were reported for serum homocysteine with serum ferritin, vitamin B12, hemoglobin, and hematocrit levels.CONCLUSION: Important associations were found between serum homocysteine and markers of iron deficiency. Monitoring homocysteine levels might be essential to understand the development of different clinical conditions including anemia. It seems necessary to conduct prospective trials to determine whether treating anemia ameliorates homocysteine levels.

  2. Photocatalytic characteristics of single phase Fe-doped anatase TiO2 nanoparticles sensitized with vitamin B12

    International Nuclear Information System (INIS)

    Gharagozlou, Mehrnaz; Bayati, R.

    2015-01-01

    Highlights: • Anatase TiO 2 /B 12 hybrid nanostructured catalyst was successfully synthesized by sol–gel technique. • The nanoparticle catalyst was doped with iron at several concentrations. • Nanoparticles were characterized in detail by XRD, Raman, TEM, EDS, and spectroscopy techniques. • The formation mechanism and role of point defects on photocatalytic properties were discussed. • A structure-property-processing correlation was established. - Abstract: We report a processing-structure-property correlation in B 12 -anatase titania hybrid catalysts doped with several concentrations of iron. Our results clearly show that low-level iron doping alters structure, defect content, and photocatalytic characteristics of TiO 2 . XRD and Raman studies revealed formation of a single-phase anatase TiO 2 where no iron based segregation in particular iron oxide, was detected. FT-IR spectra clearly confirmed sensitization of TiO 2 nanoparticles with vitamin B 12 . TEM micrographs and diffraction patterns confirmed crystallization of anatase nanoparticles with a radius of 15–20 nm. Both XRD and Raman signals showed a peak shift and a peak broadening which are surmised to originate from creation of point defects, namely oxygen vacancy and titanium interstitial. The doped samples revealed a narrower band gap as compared to undoped samples. Photocatalytic activity of the samples was assessed through measuring the decomposition rate of rhodamine B. It was found that sensitization with vitamin B 12 and Fe-doping significantly enhances the photocatalytic efficiency of the anatase nanoparticles. We also showed that there is an optimum Fe-doping level where the maximum photocatalytic activity is achieved. The boost of photocatalytic activity was qualitatively understood to originate from a more effective use of the light photons, formation of point defects, which enhance the charge separation, higher carrier mobility

  3. Pengaruh asupan Fe, vitamin A, vitamin B12, dan vitamin C terhadap kadar hemoglobin pada remaja vegan

    Directory of Open Access Journals (Sweden)

    Damayanti Siallagan

    2016-10-01

    Full Text Available Background: Vegan has become a diet that started to be many people's choice. Low intake of iron and vitamin B12 is factors that can cause anemia in vegan. On the other side vegans often consume vegetables and fruits that contained high of vitamin A and vitamin C which helps the absorption of iron, that can help prevent anemia. Objective: The purpose of the research know the effect of the intake of iron, vitamin A, vitamin B12, vitamin C on hemoglobin (Hblevels in young Buddhist vegan Pusdiklat Maitreyawira. Method: This research uses cross-sectional design. The population in this study are all adolescent vegan in the Buddhist Pusdiklat Maitreyawira. Samples in this study were 31 peoples. Independent variable is an intake of iron, vitamin A, vitamin B12, and vitamin C was obtained by SQ-FFQ, while the dependent variable was Hb with hemoglobin testing system quick-check set. Analysis of the data in this study using Pearson correlation and multiple linear regression. Results: There is a relationship intake of iron (p=0,000, vitamin B12 (p=0,037, and vitamin C (p=0,000 to Hb level of adolescent vegan in Buddhist Pusdiklat Maitreyawira, there is no relationship intake of vitamin A with a Hb level of adolescent vegan (p=0,220. The result of multivariate analysis using multiple regression analysis of the variables that most influence haemoglobin levels of adolescent vegan are the intake of iron and vitamin C. Each increase of 1 mg Fe intake will increase the Hb concentration as much as 0.013 g/dl and increase of 1 mg of vitamin C intake will increase Hb levels as much as 0.002 g/dl. Conclusion: Iron and vitamin C intake is the most influence factors to hemoglobin levels of adolescent vegan in Buddhist Pusdiklat Maitreyawira.

  4. Route and Type of Formulation Administered Influences the Absorption and Disposition of Vitamin B12 Levels in Serum

    Directory of Open Access Journals (Sweden)

    Luis Vitetta

    2018-01-01

    Full Text Available The administration of biological compounds that optimize health benefits is an ever-evolving therapeutic goal. Pharmaceutical and other adjunctive biological compounds have been administered via many different routes in order to produce a systemic pharmacological effect. The article summarizes the findings from an Australian comparative study in adults administered vitamin B12 through different oral delivery platforms. A total of 16 subjects (9 males, 7 females voluntarily partook in a comparative clinical study of five different vitamin B12 formulations across a six-month period, completing 474 person-hours of cumulative contribution, that was equivalent to an n = 60 participation. A nanoparticle delivered vitamin B12 through a NanoCelle platform was observed to be significantly (p < 0.05 better absorbed than all other dose equivalent platforms (i.e., tablets, emulsions, or liposomes from baseline to 1, 3, and 6 h of the study period. The nanoparticle platform delivered vitamin B12 demonstrated an enhanced and significant absorption profile as exemplified by rapid systemic detection (i.e., 1 h from baseline when administered to the oro-buccal mucosa with no reports of any adverse events of toxicity. The nanoparticle formulation of methylcobalamin (1000 µg/dose in 0.3 mL volume showed bioequivalence only with a chewable-dissolvable tablet that administered a five times higher dose of methylcobalamin (5000 µg per tablet. This study has demonstrated that an active metabolite embedded in a functional biomaterial (NanoCelle may constitute a drug delivery method that can better access the circulatory system.

  5. Photocurrent response of B12As2 crystals to blue light, and its temperature- dependent electrical characterizations

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    R. Gul

    2016-02-01

    Full Text Available With the global shortage of 3He gas, researchers worldwide are looking for alternative materials for detecting neutrons. Among the candidate materials, semiconductors are attractive because of their light weight and ease in handling. Currently, we are looking into the suitability of boron arsenide (B12As2 for this specific application. As the first step in evaluating the material qualitatively, the photo-response of B12As2 bulk crystals to light with different wavelengths was examined. The crystals showed photocurrent response to a band of 407- and 470- nm blue light. The maximum measured photoresponsivity and the photocurrent density at 0.7 V for 470 nm blue light at room temperature were 0.25 A ⋅ W−1 and 2.47 mA ⋅ cm−2, respectively. In addition to photo current measurements, the electrical properties as a function of temperature (range: 50-320 K were measured. Reliable data were obtained for the low-temperature I-V characteristics, the temperature dependence of dark current and its density, and the resistivity variations with temperature in B12As2 bulk crystals. The experiments showed an exponential dependence on temperature for the dark current, current density, and resistivity; these three electrical parameters, respectively, had a variation of a few nA to μA, 1-100 μA ⋅ cm−2 and 7.6x105-7.7x103 Ω ⋅ cm, for temperature increasing from 50 K to 320 K. The results from this study reported the first photoresponse and demonstrated that B12As2 is a potential candidate for thermal-neutron detectors.

  6. Reducción de órganohalogenados mediada por vitamina B12 y citrato de titanio (III en microemulsiones bicontinuas

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    Lorean Madriz

    2012-05-01

    Full Text Available We studied the electrochemical behavior of both the titanium citrate and the vitamin B12 in bicontinuous microemulsions for the reduction of halogenated organic compounds. The reduced form of titanium citrate complex, Ti(III-cit, prepared by electrolysis, transforms, in a homogeneous way, the vitamin B12 to their reduced (B12r and super reduced (B12s forms; the latter form (B12s easily promotes dehalogenation of organic compounds in microemulsion. Benzyl chloride, for example, was dehalogenated in a short period of time transforming the original amount between 46 and 85%; on the other hand, lindane disappeared completely when it was in the presence of vitamin B12 while no effect was observed for 1,2–dichloroethane

  7. Antifungal performance of extracellular chitinases and culture supernatants of Streptomyces galilaeus CFFSUR-B12 against Mycosphaerella fijiensis Morelet.

    Science.gov (United States)

    Castillo, Benjamín Moreno; Dunn, Michael F; Navarro, Karina Guillén; Meléndez, Francisco Holguín; Ortiz, Magdalena Hernández; Guevara, Sergio Encarnación; Palacios, Graciela Huerta

    2016-03-01

    The tropical and mycoparasite strain Streptomyces galilaeus CFFSUR-B12 was evaluated as an antagonist of Mycosphaerella fijiensis Morelet, causal agent of the Black Sigatoka Disease (BSD) of banana. On zymograms of CFFSUR-B12 culture supernatants, we detected four chitinases of approximately 32 kDa (Chi32), 20 kDa (Chi20), and two with masses well over 170 kDa (ChiU) that showed little migration during denaturing electrophoresis at different concentrations of polyacrylamide. The thymol-sulphuric acid assay showed that the ChiU were glycosylated chitinases. Moreover, matrix assisted laser desorption ionization time-of-flight MS analysis revealed that the ChiU are the same protein and identical to a family 18 chitinase from Streptomyces sp. S4 (gi|498328075). Chi32 was similar to an extracellular protein from Streptomyces albus J1074 (gi|478687481) and Chi20 was non-significantly similar to chitinases from five different strains of Streptomyces (P > 0.05). Subsequently, Chi32 and Chi20 were partially purified by anion exchange and hydrophobic interaction chromatography and tested against M. fijiensis. Chitinases failed to inhibit ascospore germination, but inhibited up to 35 and 62% of germ tube elongation and mycelial growth, respectively. We found that crude culture supernatant and living cells of S. galilaeus CFFSUR-B12 were the most effective in inhibiting M. fijiensis and are potential biocontrol agents of BSD.

  8. Specific features of magnetoresistance during the antiferromagnet—paramagnet transition in Tm1−xYbxB12

    International Nuclear Information System (INIS)

    Sluchanko, N. E.; Azarevich, A. N.; Bogach, A. V.; Glushkov, V. V.; Demishev, S. V.; Levchenko, A. V.; Filippov, V. B.; Shitsevalova, N. Yu.

    2013-01-01

    The transverse magnetoresistance Δρ/ρ(H, T) of Tm 1−x Yb x B 12 single crystals is studied in the ytterbium concentration range corresponding to the antiferromagnet-paramagnet transition in a magnetic field up to 80 kOe at low temperatures. A magnetic H-T phase diagram is constructed for the antiferromagnetic state of substitutional Tm 1−x Yb x B 12 solid solutions with x ≤ 0.1. The contributions to the magnetoresistance in the antiferromagnetic and paramagnetic phases of the dodecaborides under study are separated. Along with negative quadratic magnetoresistance -Δρ/ρ ∝ H 2 , the magnetically ordered phase of these compounds is found to have component Δρ/ρ ∝ H that linearly changes in a magnetic field. The negative contribution to the magnetoresistance of Tm 1−x Yb x B 12 is analyzed in terms of the Yosida model for a local magnetic susceptibility.

  9. A Potential Epigenetic Marker Mediating Serum Folate and Vitamin B12 Levels Contributes to the Risk of Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Loo Keat Wei

    2015-01-01

    Full Text Available Stroke is a multifactorial disease that may be associated with aberrant DNA methylation profiles. We investigated epigenetic dysregulation for the methylenetetrahydrofolate reductase (MTHFR gene among ischemic stroke patients. Cases and controls were recruited after obtaining signed written informed consents following a screening process against the inclusion/exclusion criteria. Serum vitamin profiles (folate, vitamin B12, and homocysteine were determined using immunoassays. Methylation profiles for CpGs A and B in the MTHFR gene were determined using a bisulfite-pyrosequencing method. Methylation of MTHFR significantly increased the susceptibility risk for ischemic stroke. In particular, CpG A outperformed CpG B in mediating serum folate and vitamin B12 levels to increase ischemic stroke susceptibility risks by 4.73-fold. However, both CpGs A and B were not associated with serum homocysteine levels or ischemic stroke severity. CpG A is a potential epigenetic marker in mediating serum folate and vitamin B12 to contribute to ischemic stroke.

  10. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptides...... can be modified to obtain desired properties or conformation, tagged for purification, isotopically labeled for protein quantitation or conjugated to immunogens for antibody production. The antibodies that bind to these peptides represent an invaluable tool for biological research and discovery....... To better understand the underlying mechanisms of antibody-antigen interaction here we present a pipeline developed by us to structurally classify immunoglobulin antigen binding sites and to infer key sequence residues and other variables that have a prominent role in each structural class....

  11. Designing two-in-one antibodies.

    Science.gov (United States)

    Valladares, Ignacio Garcia; Espinoza, Luis R

    2009-09-01

    Evaluation of: Bostrom J, Shang-Fan Y, Kan D et al.: Variants of the antibody Herceptin that interact with HER2 and VEGF at the antigen binding site. Science 323, 1610-1614 (2009). The longstanding held notion that one antibody equals one antigen and, hence, one function has been challenged in recent years. Improved technology in antibody production, especially the accumulation of sequence data of immunoglobulin genes and the advent of PCR have made it possible to clone