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Sample records for choline

  1. Choline Magnesium Trisalicylate

    Science.gov (United States)

    Choline magnesium trisalicylate is used to relieve the pain, tenderness, inflammation (swelling), and stiffness caused by arthritis and painful ... used to relieve pain and lower fever. Choline magnesium trisalicylate is in a class of nonsteroidal anti- ...

  2. Dietary Reference Values for choline

    DEFF Research Database (Denmark)

    Sjödin, Anders Mikael

    2016-01-01

    Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derives Dietary Reference Values (DRVs) for choline. In this Opinion, the Panel considers dietary choline including choline compounds (e.g. glycerophosphocholine, phosphocholine...

  3. A brief history of choline

    Science.gov (United States)

    Zeisel, Steven H.

    2015-01-01

    In 1850, Theodore Gobley, working in Paris, described a substance “lecithine”, which he named after the Greek “lekithos” for egg yolk. Adolph Strecker noted in 1862 that when lecithin from bile was heated, it generated a new nitrogenous chemical that he named “choline”. Three years later, Oscar Liebreich identified a new substance, “neurine”, in the brain. After a period of confusion, neurine and choline were found to be the same molecule, and the name choline was adapted. Lecithin was eventually characterized chemically as being phosphatidylcholine. In 1954, Eugene Kennedy described the cytidine 5-dihphosphocholine pathway by which choline is incorporated into phosphatidylcholine. A second route, the phosphatidylethanolamine-N-methyltransferase pathway, was identified by Jon Bremer and David Greenberg in 1960. The role of choline as part of the neurotransmitter acetylcholine was established by Otto Loewi and Henry Dale. Working in the 1930s at the University of Toronto, Charles Best showed that choline prevented fatty liver in dogs and rats. The importance of choline as an essential nutrient for human health was determined in the 1990s through controlled feeding studies in humans. Recently, an understanding of the role of genetic variation in setting the dietary requirement for choline in people is being unraveled. PMID:23183298

  4. Evaluation of the choline status in mink fed different levels and sources of choline

    DEFF Research Database (Denmark)

    Hedemann, Mette Skou; Damgaard, Birthe Marie; Clausen, T.N.

    2012-01-01

    Choline is an essential nutrient but the daily need for choline in mink has never been determined. Two experiments were performed to evalutate the choline status in mink kits and full-grown mink fed different levels of choline. In the first experiment mink kits were fed a synthetic diet with chol...

  5. 21 CFR 582.5252 - Choline chloride.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Choline chloride. 582.5252 Section 582.5252 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5252 Choline chloride. (a) Product. Choline chloride. (b) Conditions of use. This...

  6. Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations

    Directory of Open Access Journals (Sweden)

    Ariel B. Ganz

    2017-01-01

    Full Text Available Single nucleotide polymorphisms (SNPs in choline metabolizing genes are associated with disease risk and greater susceptibility to organ dysfunction under conditions of dietary choline restriction. However, the underlying metabolic signatures of these variants are not well characterized and it is unknown whether genotypic differences persist at recommended choline intakes. Thus, we sought to determine if common genetic risk factors alter choline dynamics in pregnant, lactating, and non-pregnant women consuming choline intakes meeting and exceeding current recommendations. Women (n = 75 consumed 480 or 930 mg choline/day (22% as a metabolic tracer, choline-d9 for 10–12 weeks in a controlled feeding study. Genotyping was performed for eight variant SNPs and genetic differences in metabolic flux and partitioning of plasma choline metabolites were evaluated using stable isotope methodology. CHKA rs10791957, CHDH rs9001, CHDH rs12676, PEMT rs4646343, PEMT rs7946, FMO3 rs2266782, SLC44A1 rs7873937, and SLC44A1 rs3199966 altered the use of choline as a methyl donor; CHDH rs9001 and BHMT rs3733890 altered the partitioning of dietary choline between betaine and phosphatidylcholine synthesis via the cytidine diphosphate (CDP-choline pathway; and CHKA rs10791957, CHDH rs12676, PEMT rs4646343, PEMT rs7946 and SLC44A1 rs7873937 altered the distribution of dietary choline between the CDP-choline and phosphatidylethanolamine N-methyltransferase (PEMT denovo pathway. Such metabolic differences may contribute to disease pathogenesis and prognosis over the long-term.

  7. Neuroprotective Actions of Dietary Choline

    Directory of Open Access Journals (Sweden)

    Jan Krzysztof Blusztajn

    2017-07-01

    Full Text Available Choline is an essential nutrient for humans. It is a precursor of membrane phospholipids (e.g., phosphatidylcholine (PC, the neurotransmitter acetylcholine, and via betaine, the methyl group donor S-adenosylmethionine. High choline intake during gestation and early postnatal development in rat and mouse models improves cognitive function in adulthood, prevents age-related memory decline, and protects the brain from the neuropathological changes associated with Alzheimer’s disease (AD, and neurological damage associated with epilepsy, fetal alcohol syndrome, and inherited conditions such as Down and Rett syndromes. These effects of choline are correlated with modifications in histone and DNA methylation in brain, and with alterations in the expression of genes that encode proteins important for learning and memory processing, suggesting a possible epigenomic mechanism of action. Dietary choline intake in the adult may also influence cognitive function via an effect on PC containing eicosapentaenoic and docosahexaenoic acids; polyunsaturated species of PC whose levels are reduced in brains from AD patients, and is associated with higher memory performance, and resistance to cognitive decline.

  8. Relationship Between Organophosphate Toxicity and Choline Metabolism

    Science.gov (United States)

    1986-06-06

    Results from studies on the actions of the organophosphates on the central nervus system have suggested that these compounds, through an action on...Grganophosphates alter the disposition and metabolism of choline and choline-containing compounds in the nervous system , the relationshi ý of these changes to...mechanisms regulating the metabolism of choline, as well as the specific interactions of the organophospha:es with biochemical systems , may differ

  9. 21 CFR 182.8252 - Choline chloride.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Choline chloride. 182.8252 Section 182.8252 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... chloride. (a) Product. Choline chloride. (b) Conditions of use. This substance is generally recognized as...

  10. Choline Theft-An Inside Job.

    Science.gov (United States)

    Mora-Ortiz, Marina; Claus, Sandrine Paule

    2017-09-13

    Choline is a crucial methyl donor necessary for epigenetic regulation. In this issue of Cell Host & Microbe, Romano et al. (2017) demonstrate that choline-utilizing gut bacteria compete with their host for this essential resource, calling for a systematic consideration of gut microbial composition for personalized diet recommendations. Copyright © 2017. Published by Elsevier Inc.

  11. Factors influencing erythrocyte choline concentrations.

    Science.gov (United States)

    Miller, B L; Jenden, D J; Tang, C; Read, S

    1989-01-01

    Choline concentrations in human erythrocytes increase after freezing and thawing, during incubation in Krebs-phosphate for 30 min or on storage at 0 degrees C for 3-24 hr. The increase is prevented by protein precipitation by 10% perchloric acid, 10% zinc hydroxide, 10% sodium tungstate or boiling in water. It is not prevented by EDTA (10 mM) and is increased by oleate (5 mM). We suggest that the increase is due to the action of phospholipase D on erythrocyte phospholipids.

  12. The effect of cytidine-diphosphate choline (CDP-choline) on brain lipid changes during aging

    International Nuclear Information System (INIS)

    De Medio, G.E.; Trovarelli, G.; Piccinin, G.L.; Porcellati, G.

    1984-01-01

    Lipid synthesis has been tested in vivo in different brain areas of 12-month-old male rats. Cortex, striatum, brainstem, and subcortex of brain have been examined. The cerebellum was discarded. Mixtures of (2- 3 H)glycerol and (Me- 14 C)choline were injected into the lateral ventricle of the brain as lipid precursors, and their incorporation into total lipid, water-soluble intermediates and choline-containing phospholipids was examined 1 hr after isotope injection. In another series of experiments cytidine-5'-diphosphate choline (CDP-choline) was injected intraventricularly to the aged rats 10 min before sacrifice with a simultaneous injection, and radioactivity assays were performed as above. Distribution of radioactivity content of CDP-choline among brain areas 10 min after its administration showed a noticeable enrichment of the nucleotide and water-soluble-related compounds in the examined areas, but to a lesser degree in the cerebral cortex. The incorporation of labelled glycerol, which is severely depressed in aged rats in all four areas [Gaiti et al, 1982, 1983], was increased only in the cortex, and apparently decreased in the other areas. This last result is probably due to a dilution effect brought about by the administered cold CDP-choline upon the ( 14 C)-containing water-soluble metabolites. As a consequence, the ( 3 H)/( 14 C) ratio in total lipid and in isolated phosphatidylcholine and choline plasmalogen increased after CDP-choline treatment

  13. The efflux of choline from nerve cells: mediation by ionic gradients and functional exchange of choline from glia to neurons

    International Nuclear Information System (INIS)

    Hoffmann, D.; Ferret, B.; Massarelli, R.; Mykita, S.

    1986-01-01

    This paper analyzes the relationship between ions and the efflux of choline, and suggests the possibility of a balance effect for choline fluxes which is produced and maintained by ioinic gradients. It is also suggested that glial cells may actively exchange choline with neurons during nerve actively exchange choline with neurons during nerve activity, and that they may function as a choline reservoir for neuronal needs. The study shows that neurons and glial cells spontaneously discharge choline into the incubation medium. The exiting choline is essentially of free origin, as can be seen in an illustration provided. Neurons and glial cells had been prelabelled with ( 14 C) choline overnight, and labelled for 15 min with tritium-choline. The higher amount of tritium-choline exiting the cells indicates that it is the freshly labelled choline which is preferentially released. The remaining of ( 14 C) - choline exiting the cells corresponds to the free choline of phospholipid origin which amounts to about one third of the total free choline content

  14. Choline or methionine reverses impaired secretion of VLDL by hepatocytes from choline-deficient rats

    International Nuclear Information System (INIS)

    Yao, Z.; Vance, D.E.

    1987-01-01

    Male rats fed a choline-deficient (CD) diet for three days accumulated triacylglycerol (TG) in the liver. Hepatocytes from these rats were cultured and maintained in a medium + choline. The rate of secretion of TG was reduced by 50% in the CD cells. Correspondingly, [ 3 H]oleate and [ 3 H]glycerol were incorporated at a 2-fold higher rate into TG secreted by choline-supplemented cells compared to CD cells. Isolation of lipoprotein fractions by ultracentrifugation showed that the reduced secretion of TG by CD hepatocytes was mainly due to an impaired secretion of very low density lipoprotein (VLDL). Incorporation of [ 3 H]leucine into secreted apoB/sub H/, apoB/sub L/ and apoE was markedly reduced in CD cells compared to choline-supplemented cells. Secretion of high density lipoprotein was not reduced in the CD hepatocytes. Normal secretion of VLDL was resumed upon addition of methionine to the CD cells

  15. Choline-PET/CT for imaging prostate cancer; Cholin-PET/CT zur Bildgebung des Prostatakarzinoms

    Energy Technology Data Exchange (ETDEWEB)

    Krause, Bernd Joachim [Klinik- und Poliklinik fuer Nuklearmedizin, Klinikum rechts der Isar, Technische Univ. Muenchen (Germany); Treiber, U.; Schwarzenboeck, S.; Souvatzoglou, M. [Klinik fuer Urologie, Klinikum rechts der Isar, Technische Univ. Muenchen (Germany)

    2010-09-15

    PET and PET/CT using [{sup 11}C]- and [{sup 18}F]-labelled choline derivatives are increasingly being used for imaging of prostate cancer. The value of PET and PET/CT with [{sup 11}C]- and [{sup 18}F]-labelled choline derivates in biochemical recurrence of prostate cancer has been examined in many studies and demonstrates an increasing importance. Primary prostate cancer can be detected with moderate sensitivity using PET and PET/CT using [{sup 11}C]- and [{sup 18}F]-labelled choline derivatives - the differentiation between benign prostatic hyperplasia, prostatitis or high-grade intraepithelial neoplasia (HGPIN) is not always possible. At the present time [{sup 11}C]choline PET/CT is not recommended in the primary setting but may be utilized in clinically suspected prostate cancer with repeatedly negative prostate biopsies, in preparation of a focused re-biopsy. Promising results have been obtained for the use of PET and PET/CT with [{sup 11}C]- and [{sup 18}F]-labelled choline derivates in patients with biochemical recurrence. The detection rate of choline PET and PET/CT for local, regional, and distant recurrence in patients with a biochemical recurrence shows a linear correlation with PSA values at the time of imaging and reaches about 75% in patients with PSA > 3 ng/mL. At PSA values below 1 ng/mL, the recurrence can be diagnosed with choline PET/CT in approximately 1/3 of the patients. PET and PET/CT with [{sup 11}C]- and [{sup 18}F]choline derivates can be helpful for choosing a therapeutic strategy in the sense of an individualized treatment: since an early diagnosis of recurrence is crucial to the choice of optimal treatment. The localization of the site of recurrence - local recurrence, lymph node metastasis or systemic dissemination - has important influence on the therapy regimen. (orig.)

  16. Choline and Choline Metabolite Patterns and Associations in Blood and Milk during Lactation in Dairy Cows

    Science.gov (United States)

    Artegoitia, Virginia M.; Middleton, Jesse L.; Harte, Federico M.; Campagna, Shawn R.; de Veth, Michael J.

    2014-01-01

    Milk and dairy products are an important source of choline, a nutrient essential for human health. Infant formula derived from bovine milk contains a number of metabolic forms of choline, all contribute to the growth and development of the newborn. At present, little is known about the factors that influence the concentrations of choline metabolites in milk. The objectives of this study were to characterize and then evaluate associations for choline and its metabolites in blood and milk through the first 37 weeks of lactation in the dairy cow. Milk and blood samples from twelve Holstein cows were collected in early, mid and late lactation and analyzed for acetylcholine, free choline, betaine, glycerophosphocholine, lysophosphatidylcholine, phosphatidylcholine, phosphocholine and sphingomyelin using hydrophilic interaction liquid chromatography-tandem mass spectrometry, and quantified using stable isotope-labeled internal standards. Total choline concentration in plasma, which was almost entirely phosphatidylcholine, increased 10-times from early to late lactation (1305 to 13,535 µmol/L). In milk, phosphocholine was the main metabolite in early lactation (492 µmol/L), which is a similar concentration to that found in human milk, however, phosphocholine concentration decreased exponentially through lactation to 43 µmol/L in late lactation. In contrast, phosphatidylcholine was the main metabolite in mid and late lactation (188 µmol/L and 659 µmol/L, respectively), with the increase through lactation positively correlated with phosphatidylcholine in plasma (R 2 = 0.78). Unlike previously reported with human milk we found no correlation between plasma free choline concentration and milk choline metabolites. The changes in pattern of phosphocholine and phosphatidylcholine in milk through lactation observed in the bovine suggests that it is possible to manufacture infant formula that more closely matches these metabolites profile in human milk. PMID:25157578

  17. Choline and choline metabolite patterns and associations in blood and milk during lactation in dairy cows.

    Directory of Open Access Journals (Sweden)

    Virginia M Artegoitia

    Full Text Available Milk and dairy products are an important source of choline, a nutrient essential for human health. Infant formula derived from bovine milk contains a number of metabolic forms of choline, all contribute to the growth and development of the newborn. At present, little is known about the factors that influence the concentrations of choline metabolites in milk. The objectives of this study were to characterize and then evaluate associations for choline and its metabolites in blood and milk through the first 37 weeks of lactation in the dairy cow. Milk and blood samples from twelve Holstein cows were collected in early, mid and late lactation and analyzed for acetylcholine, free choline, betaine, glycerophosphocholine, lysophosphatidylcholine, phosphatidylcholine, phosphocholine and sphingomyelin using hydrophilic interaction liquid chromatography-tandem mass spectrometry, and quantified using stable isotope-labeled internal standards. Total choline concentration in plasma, which was almost entirely phosphatidylcholine, increased 10-times from early to late lactation (1305 to 13,535 µmol/L. In milk, phosphocholine was the main metabolite in early lactation (492 µmol/L, which is a similar concentration to that found in human milk, however, phosphocholine concentration decreased exponentially through lactation to 43 µmol/L in late lactation. In contrast, phosphatidylcholine was the main metabolite in mid and late lactation (188 µmol/L and 659 µmol/L, respectively, with the increase through lactation positively correlated with phosphatidylcholine in plasma (R2 = 0.78. Unlike previously reported with human milk we found no correlation between plasma free choline concentration and milk choline metabolites. The changes in pattern of phosphocholine and phosphatidylcholine in milk through lactation observed in the bovine suggests that it is possible to manufacture infant formula that more closely matches these metabolites profile in human milk.

  18. A comparison of choline:urea and choline:oxalic acid deep eutectic solvents at 338 K

    Science.gov (United States)

    Gilmore, Mark; Moura, Leila M.; Turner, Adam H.; Swadźba-Kwaśny, Małgorzata; Callear, Samantha K.; McCune, Jade A.; Scherman, Oren A.; Holbrey, John D.

    2018-05-01

    1:2 choline chloride:urea and 1:1 choline chloride:oxalic acid deep eutectic solvents are compared at 338 K using liquid-phase neutron diffraction with H/D isotopic substitution to obtain differential neutron scattering cross sections and fitting of models to the experimental data using Empirical Potential Structure Refinement. In comparison to the previously reported study of choline chloride:urea at 303 K, we observed significant weakening and lengthening of choline-OH⋯Cl- and choline-OH⋯hydrogen-bond acceptor correlations.

  19. New approaches to the synthesis of diclofenac choline

    Directory of Open Access Journals (Sweden)

    Elżbieta Dąbrowska-Maś

    2017-07-01

    Full Text Available The process described herein proceeds to obtaining diclofenac choline from choline bicarbonate and diclofenac acid in mild conditions, using non-toxic solvent, with the same impurity profile deriving from diclofenac particle as for diclofenac sodium EP. The substance is also substantially free from impurities deriving from choline and free from inorganic by-products, what means that the quality may be accepted for use as an active substance in medicine.

  20. Formulation and utilization of choline based samples for dissolution dynamic nuclear polarization

    DEFF Research Database (Denmark)

    Bowen, Sean; Ardenkjær-Larsen, Jan Henrik

    2013-01-01

    their performance to more traditional sample formulations. Choline yields stable samples with exceptional polarization performance while simultaneously offering the capability to easily remove the choline after dissolution, perform experiments with the hyperpolarized choline, or anything in between....

  1. Contents of lecithin and choline in crude drugs.

    Science.gov (United States)

    Yamasaki, K; Kikuoka, M; Nishi, H; Kokusenya, Y; Miyamoto, T; Matsuo, M; Sato, T

    1994-01-01

    The determination of lecithin and choline in crude drugs was established by a combination of high performance liquid chromatography (HPLC) with electrochemical detector (ECD) and enzyme reaction. Lecithin in crude drugs extracted with a mixture of chloroform-methanol (2:1) at room temperature was hydrolyzed by phospholipase D. The hydrolyzate was injected to HPLC, and choline was separated from impurities by reverse phase column. The choline was converted to betaine and hydrogen peroxide by passing through column packed with immobilized choline oxidase. This hydrogen peroxide was detected by ECD. The peak area of hydrogen peroxide derived from lecithin was proportional to the concentration of lecithin from 0.10 to 1.52 microgram/ml. Choline in crude drugs was extracted with ethanol under reflux and determined under the same HPLC conditions as lecithin. The peak area of hydrogen peroxide derived from choline was proportional to the concentration of choline from 0.01 to 0.45 microgram/ml. The contents of lecithin and choline in 31 kinds of crude drugs were determined by these established methods. The results showed that Cervi Parvum Cornu, Kokurozin, Foenigraeci Semen and Psoraleae Semen contained more lecithin than other crude drugs, while Angelicae Radix, Foenigraeci Semen, Psoraleae Semen, and especially Hippocampus were found to contain more choline than other crude drugs.

  2. Choline transport via choline transporter-like protein 1 in conditionally immortalized rat syncytiotrophoblast cell lines TR-TBT.

    Science.gov (United States)

    Lee, N-Y; Choi, H-M; Kang, Y-S

    2009-04-01

    Choline is an essential nutrient for phospholipids and acetylcholine biosynthesis in normal development of fetus. In the present study, we investigated the functional characteristics of choline transport system and inhibitory effect of cationic drugs on choline transport in rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT). Choline transport was weakly Na(+) dependent and significantly influenced by extracellular pH and by membrane depolarization. The transport process of choline is saturable with Michaelis-Menten constants (K(m)) of 68microM and 130microM in TR-TBT 18d-1 and TR-TBT 18d-2 respectively. Choline uptake in the cells was inhibited by unlabeled choline and hemicholinium-3 as well as various organic cations including guanidine, amiloride and acetylcholine. However, the prototypical organic cation tetraethylammonium and cimetidine showed very little inhibitory effect of choline uptake in TR-TBT cells. RT-PCR revealed that choline transporter-like protein 1 (CTL1) and organic cation transporter 2 (OCT2) are expressed in TR-TBT cells. The transport properties of choline in TR-TBT cells were similar or identical to that of CTL1 but not OCT2. CTL1 was also detected in human placenta. In addition, several cationic drugs such as diphenhydramine and verapamil competitively inhibited choline uptake in TR-TBT 18d-1 with K(i) of 115microM and 55microM, respectively. Our results suggest that choline transport system, which has intermediate affinity and weakly Na(+) dependent, in TR-TBT seems to occur through a CTL1 and this system may have relevance with the uptake of pharmacologically important organic cation drugs.

  3. 21 CFR 172.370 - Iron-choline citrate complex.

    Science.gov (United States)

    2010-04-01

    ....370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.370 Iron-choline citrate complex. Iron-choline...

  4. CDP-choline modulates matrix metalloproteinases in rat sciatic injury.

    Science.gov (United States)

    Gundogdu, Elif Basaran; Bekar, Ahmet; Turkyilmaz, Mesut; Gumus, Abdullah; Kafa, Ilker Mustafa; Cansev, Mehmet

    2016-02-01

    CDP-choline (cytidine-5'-diphosphocholine) improves functional recovery, promotes nerve regeneration, and decreases perineural scarring in rat peripheral nerve injury. The aim of the present study was to investigate the mechanism of action of CDP-choline with regard to matrix metalloproteinase (MMP) activity in the rat-transected sciatic nerve injury model. Male Wistar rats were randomized into Sham, Saline, and CDP-choline groups. Rats in Sham group received Sham surgery, whereas rats in Saline and CDP-choline groups underwent right sciatic nerve transection followed by immediate primary saturation and injected intraperitoneally with 0.9% NaCl (1 mL/kg) and CDP-choline (600 μg/kg), respectively. Sciatic nerve samples were obtained 1, 3, and 7 d after the surgery and analyzed for levels and activities of MMP-2 and MMP-9, levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-3, and axonal regeneration. CDP-choline treatment decreased the levels and activities of MMP-2 and MMP-9, whereas increasing levels of TIMP-1 and TIMP-3 significantly on the third and seventh day after injury compared to Saline group. In addition, CDP-choline administration resulted in new axon formation and formation and advancement of myelination on newly formed islets (compartments) of axonal regrowth. Our data show, for the first time, that CDP-choline modulates MMP activity and promotes the expression of TIMPs to stimulate axonal regeneration. These data help to explain one mechanism by which CDP-choline provides neuroprotection in peripheral nerve injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Spatial memory and hippocampal plasticity are differentially sensitive to the availability of choline in adulthood as a function of choline supply in utero

    OpenAIRE

    Wong-Goodrich, Sarah J.E.; Glenn, Melissa J.; Mellott, Tiffany J.; Blusztajn, Jan K.; Meck, Warren H.; Williams, Christina L.

    2008-01-01

    Altered dietary choline availability early in life leads to persistent changes in spatial memory and hippocampal plasticity in adulthood. Developmental programming by early choline nutrition may determine the range of adult choline intake that is optimal for the types of neural plasticity involved in cognitive function. To test this, male Sprague-Dawley rats were exposed to a choline chloride deficient (DEF), sufficient (CON), or supplemented (SUP) diet during embryonic days 12-17 and then re...

  6. The nutrigenetics and nutrigenomics of the dietary requirement for choline.

    Science.gov (United States)

    Corbin, Karen D; Zeisel, Steven H

    2012-01-01

    Advances in nutrigenetics and nutrigenomics have been instrumental in demonstrating that nutrient requirements vary among individuals. This is exemplified by studies of the nutrient choline, in which gender, single-nucleotide polymorphisms, estrogen status, and gut microbiome composition have been shown to influence its optimal intake level. Choline is an essential nutrient with a wide range of biological functions, and current studies are aimed at refining our understanding of its requirements and, importantly, on defining the molecular mechanisms that mediate its effects in instances of suboptimal dietary intake. This chapter introduces the reader to challenges in developing individual nutrition recommendations, the biological function of choline, current and future research paradigms to fully understand the consequences of inadequate choline nutrition, and some forward thinking about the potential for individualized nutrition recommendations to become a tangible application for improved health. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. RBC-choline: changes by lithium and relation to prophylactic response

    International Nuclear Information System (INIS)

    Haag, M.; Haag, H.; Eisenried, F.; Greil, W.

    1984-01-01

    Red blod cell (RBC)- and plasma-choline levels were measured in patients on lithium (n=96), antidepressants (n=32) and neuroleptics (n=51) and in 25 healthy drug-free controls. Lithium patients exhibited highly increased RBC- and slightly increased plasma-choline levels compared with controls (P<0.001 and P<0.05, respectively); the choline ratio (RBC-/plasma-choline) was elevated almost to the same extent as RBC-choline (P<0.001). With antidepressants RBC-choline and choline ratios were slightly reduced (P<0.05), whereas neuroleptics showed no effect on choline levels. 79% of lithium patients were responders (reduction in hospitalizations with lithium) 21% were non-responders (no reduction or increase in hospitalizations). Choline ratio exhibited a significant relation to prophylactic lithium response, but lithium ratio did not. The percentage of non-responders was significantly higher in patients with a choline ratio exceeding 100 than in patients with a choline ratio below this cut-off (P<0.01). Thus, the increase of RBC-choline and choline ratios appears to be an effect specific for lithium and might be related to the outcome of lithium prophylaxis. (author)

  8. Phosphorylation of the Yeast Choline Kinase by Protein Kinase C

    Science.gov (United States)

    Choi, Mal-Gi; Kurnov, Vladlen; Kersting, Michael C.; Sreenivas, Avula; Carman, George M.

    2005-01-01

    The Saccharomyces cerevisiae CKI1-encoded choline kinase catalyzes the committed step in phosphatidylcholine synthesis via the Kennedy pathway. The enzyme is phosphorylated on multiple serine residues, and some of this phosphorylation is mediated by protein kinase A. In this work, we examined the hypothesis that choline kinase is also phosphorylated by protein kinase C. Using choline kinase as a substrate, protein kinase C activity was dose- and time-dependent, and dependent on the concentrations of choline kinase (Km = 27 μg/ml) and ATP (Km = 15 μM). This phosphorylation, which occurred on a serine residue, was accompanied by a 1.6-fold stimulation of choline kinase activity. The synthetic peptide SRSSS25QRRHS (Vmax/Km = 17.5 mM-1 μmol min-1 mg-1) that contains the protein kinase C motif for Ser25 was a substrate for protein kinase C. A Ser25 to Ala (S25A) mutation in choline kinase resulted in a 60% decrease in protein kinase C phosphorylation of the enzyme. Phosphopeptide mapping analysis of the S25A mutant enzyme confirmed that Ser25 was a protein kinase C target site. In vivo, the S25A mutation correlated with a decrease (55%) in phosphatidylcholine synthesis via the Kennedy pathway whereas an S25D phosphorylation site mimic correlated with an increase (44%) in phosphatidylcholine synthesis. Whereas the S25A (protein kinase C site) mutation did not affect the phosphorylation of choline kinase by protein kinase A, the S30A (protein kinase A site) mutation caused a 46% reduction in enzyme phosphorylation by protein kinase C. A choline kinase synthetic peptide (SQRRHS30LTRQ) containing Ser30 was a substrate (Vmax/Km = 3.0 mM−1 μmol min−1 mg−1) for protein kinase C. Comparison of phosphopeptide maps of the wild type and S30A mutant choline kinase enzymes phosphorylated by protein kinase C confirmed that Ser30 was also a target site for protein kinase C. PMID:15919656

  9. Biocompatible choline based ionic salts: Solubility in short-chain alcohols

    International Nuclear Information System (INIS)

    Lopes, Joana M.; Paninho, Ana B.; Môlho, Marta F.; Nunes, Ana V.M.; Rocha, Angelo; Lourenço, Nuno M.T.; Najdanovic-Visak, Vesna

    2013-01-01

    Highlights: • Biocompatible ionic liquids based on choline esters were synthesized in this work. • Solubility of choline and choline esters based ionic salt in alcohols were measured. • Activity coefficients were calculated. • Experimental data were correlated by means of the semi-empirical Grant equation. -- Abstract: In this work, we report data on solubility of choline chloride and choline acetate in short-chain linear alcohols (ethanol, 1-propanol and 1-butanol) at various temperatures. Furthermore, we synthesize two choline derivatives: hydrogen choline chloride glutarate ([CholGlut][Cl]) and hydrogen choline chloride succinate ([CholSucc][Cl]). Their characterization and solubility in short-chain alcohols as a function of temperature are also included. Activity coefficients were calculated and their comparisons with ideal solutions were discussed. The experimental data were correlated successfully by means of the semi-empirical Grant equation

  10. Nutrition in pregnancy: the argument for including a source of choline

    OpenAIRE

    Zeisel, Steven H

    2013-01-01

    Steven H Zeisel Nutrition Research Institute at Kannapolis, Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, NC, USA Abstract: Women, during pregnancy and lactation, should eat foods that contain adequate amounts of choline. A mother delivers large amounts of choline across the placenta to the fetus, and after birth she delivers large amounts of choline in milk to the infant; this greatly increases the demand on the choline stores of the mother. Adequate inta...

  11. X-ray diffraction study of choline chloride's β form

    International Nuclear Information System (INIS)

    Petrouleas, V.; Lemmon, R.M.; Christensen, A.

    1978-01-01

    The organic salt choline chloride exists in two crystalline polymorphs. One (the α form) is extraordinarily sensitive to ionizing radiation, the other (the β form) is not. The present report describes an x-ray diffraction study of the β form. The structure has been found to be highly disordered face centered cubic. A reasonable least-square refinement of the intensity data has been achieved in the centrosymmetric space group Fm3 or Fm3m by use of a molecular model with restrained bond lengths. The results show that in the β form the electronic density due to the choline cation is closely spaced around the N, so that hydrogen bonding to the chloride is unlikely. Comparison with infrared and NMR data indicates that the disordering is dynamic and can be ascribed to rotations of the choline ion around crystallographic symmetry axes. Possible connections of these results with the radiation stability of the β form are discussed

  12. Spatial memory and hippocampal plasticity are differentially sensitive to the availability of choline in adulthood as a function of choline supply in utero.

    Science.gov (United States)

    Wong-Goodrich, Sarah J E; Glenn, Melissa J; Mellott, Tiffany J; Blusztajn, Jan K; Meck, Warren H; Williams, Christina L

    2008-10-27

    Altered dietary choline availability early in life leads to persistent changes in spatial memory and hippocampal plasticity in adulthood. Developmental programming by early choline nutrition may determine the range of adult choline intake that is optimal for the types of neural plasticity involved in cognitive function. To test this, male Sprague-Dawley rats were exposed to a choline chloride deficient (DEF), sufficient (CON), or supplemented (SUP) diet during embryonic days 12-17 and then returned to a control diet (1.1 g choline chloride/kg). At 70 days of age, we found that DEF and SUP rats required fewer choices to locate 8 baited arms of a 12-arm radial maze than CON rats. When switched to a choline-deficient diet (0 g/kg), SUP rats showed impaired performance while CON and DEF rats were unaffected. In contrast, when switched to a choline-supplemented diet (5.0 g/kg), DEF rats' performance was significantly impaired while CON and SUP rats were less affected. These changes in performance were reversible when the rats were switched back to a control diet. In a second experiment, DEF, CON, and SUP rats were either maintained on a control diet, or the choline-supplemented diet. After 12 weeks, DEF rats were significantly impaired by choline supplementation on a matching-to-place water-maze task, which was also accompanied by a decrease in dentate cell proliferation in DEF rats only. IGF-1 levels were elevated by both prenatal and adult choline supplementation. Taken together, these findings suggest that the in utero availability of an essential nutrient, choline, causes differential behavioral and neuroplastic sensitivity to the adult choline supply.

  13. Choline transport in the isolated rabbit corneal epithelium

    International Nuclear Information System (INIS)

    Faust, R.L.

    1988-01-01

    In the present study, isolated epithelial sheets were obtained by performing two sequential anterior keratectomies, three weeks apart, on rabbit corneas. Light microscopy of the isolated sheets revealed a multilayered epithelium with an intact basal cell layer without contamination from other cell types. The accumulation of [ 3 H]choline into the epithelial sheets was studied at substrate concentrations varying from 1 to 100 μMoles with and without the addition of specific metabolic and stereochemical inhibitors. Accumulation of [ 3 H]choline into these sheets was saturable. Kinetic analysis, performed by estimation from double-reciprocal plots, revealed a single component system with a K m of 24.9 μM. The metabolic inhibitors potassium cyanide and ouabain showed no effect on the uptake of [ 3 H]choline; however, the stereochemical inhibitor hemicholinium-3 significantly reduced the accumulation of radiolabel at both high and low substrate concentrations. The results suggest a non-energy dependent yet a highly specific transport system for the accumulation of choline into the rabbit epithelium

  14. Transport and phosphorylation of choline in higher plant cells. Phosphorus-31 nuclear magnetic resonance studies

    Energy Technology Data Exchange (ETDEWEB)

    Bligny, R.; Foray, M.F.; Roby, C.; Douce, R.

    1989-03-25

    When sycamore cells were suspended in basal medium containing choline, the latter was taken up by the cells very rapidly. A facilitated diffusion system appertained at low concentrations of choline and exhibited Michaelis-Menten kinetics. At higher choline concentrations simple diffusion appeared to be the principal mode of uptake. Addition of choline to the perfusate of compressed sycamore cells monitored by /sup 31/P NMR spectroscopy resulted in a dramatic accumulation of P-choline in the cytoplasmic compartment containing choline kinase and not in the vacuole. The total accumulation of P-choline over a 10-h period exhibited Michaelis-Menten kinetics. During this period, in the absence of Pi in the perfusion medium there was a marked depletion of glucose-6-P, and the cytoplasmic Pi resonance disappeared almost completely. When a threshold of cytoplasmic Pi was attained, the phosphorylation of choline was sustained by the continuous release of Pi from the vacuole although at a much lower rate. However, when 100 microM inorganic phosphate was present in the perfusion medium, externally added Pi was preferentially used to sustain P-choline synthesis. It is clear, therefore, that cytosolic choline kinase associated with a carrier-mediated transport system for choline uptake appeared as effective systems for continuously trapping cytoplasmic Pi including vacuolar Pi entering the cytoplasm.

  15. Importance of Choline as Essential Nutrient and Its Role in Prevention of Various Toxicities

    Directory of Open Access Journals (Sweden)

    Somava Biswas

    2015-01-01

    Full Text Available Choline is a water-soluble essential nutrient included as a member of the vitamin B12 group owing to its structural similarities with that of the other members of the group. Its roles and functions, however, extend much wider than that of the vitamins with which it is grouped. Choline is vital for maintenance of various key metabolic processes which play a role in the prevention or progression of various health impairments. The occurrence of diseases like neural tube defect (NTD and Alzheimer’s is prevented by the metabolic role of choline. It is also indispensable for mitigation of various forms of toxic contamination. While adequate level of choline in the body is essential, an excess of choline can result in various forms of disorder. To maintain the optimal level of choline in the body can be a challenge. The vital roles played by choline together with the range of contradictions and problems that choline presents make choline an interesting area of study. This paper attempts to summarize and review some recent publications on choline that have opened up new prospect in understanding the multiple role played by choline and in throwing light on the role played by this wonder essential nutrient in mitigating various forms of toxic contamination.

  16. Dysregulated choline metabolism in T-cell lymphoma: role of choline kinase-α and therapeutic targeting

    International Nuclear Information System (INIS)

    Xiong, J; Bian, J; Wang, L; Zhou, J-Y; Wang, Y; Zhao, Y; Wu, L-L; Hu, J-J; Li, B; Chen, S-J; Yan, C; Zhao, W-L

    2015-01-01

    Cancer cells have distinct metabolomic profile. Metabolic enzymes regulate key oncogenic signaling pathways and have an essential role on tumor progression. Here, serum metabolomic analysis was performed in 45 patients with T-cell lymphoma (TCL) and 50 healthy volunteers. The results showed that dysregulation of choline metabolism occurred in TCL and was related to tumor cell overexpression of choline kinase-α (Chokα). In T-lymphoma cells, pharmacological and molecular silencing of Chokα significantly decreased Ras-GTP activity, AKT and ERK phosphorylation and MYC oncoprotein expression, leading to restoration of choline metabolites and induction of tumor cell apoptosis/necropotosis. In a T-lymphoma xenograft murine model, Chokα inhibitor CK37 remarkably retarded tumor growth, suppressed Ras-AKT/ERK signaling, increased lysophosphatidylcholine levels and induced in situ cell apoptosis/necropotosis. Collectively, as a regulatory gene of aberrant choline metabolism, Chokα possessed oncogenic activity and could be a potential therapeutic target in TCL, as well as other hematological malignancies with interrupted Ras signaling pathways

  17. Influence of dietary protein and excess methionine on choline needs for young bobwhite quail

    Science.gov (United States)

    Serafin, J.A.

    1982-01-01

    Experiments were conducted with young Bobwhite quail (Colinus virginianus) to investigate the effect of differing dietary protein levels and nondetrimental amounts of excess methionine on choline needs. Growth and feed consumption of quail fed an adequate (27.3%) protein purified diet supplemented with 2000 mg/kg of choline were unaffected by increasing the level of excess methionine to 1.75%; however, greater amounts (2.0%, 2.25%) of excess methionine depressed growth (P less than .01), reduced feed consumption (P less than .01), and decreased feed utilization (P less than .05). Quail fed a purified diet containing 13.85% protein and 515 mg/kg of choline grew poorly. Growth was unaffected by additional choline in this diet. Growth was suboptimal among quail fed purified diets containing adequate or high (41.55%) levels of protein in which choline was limiting; however, a high level of protein did not in itself affect performance. Growth was improved by supplemental choline in these diets. Growth of quail fed purified diets with up to 1.35% excess methionine which were limiting (531 mg/kg) in choline was less than that of groups fed 2000 mg/kg of added dietary choline (P less than .01); however, excess methionine did not significantly influence growth of quail fed choline-deficient diets. These experiments indicate that neither high dietary protein nor excess methionine, fed at non-growth-depressing levels, increases dietary choline needs for young Bobwhite quail.

  18. Multimodal elucidation of choline metabolism in a murine glioma model using magnetic resonance spectroscopy and 11C-choline positron emission tomography

    NARCIS (Netherlands)

    Wehrl, H.F.; Schwab, J.; Hasenbach, K.; Reischl, G.; Tabatabai, G.; Quintanilla-Martinez, L.; Jiru, F.; Chughtai, K; Kiss, A.; Cay, F.; Bukala, D.; Heeren, R.M.A.; Pichler, B.J.; Sauter, A.W.

    2013-01-01

    The metabolites, transporters, and enzymes involved in choline metabolism are regarded as biomarkers for disease progression in a variety of cancers, but their in vivo detection is not ideal. Both magnetic resonance spectroscopy [MRS using chemical shift imaging (CSI) total choline (tCho)] and

  19. Cerium(terbium, erbium)chloride-choline chloride aqueous systems

    International Nuclear Information System (INIS)

    Gajfutdinova, R.K.; Zhuravlev, E.F.; Bikbaeva, G.G.; Domrachev, V.N.; Vanskova, G.I.

    1985-01-01

    To clarify the effect of rare earth nature on mutual solubility of rare earth salts and amines the solubility of solid phases in the systems, consisting of choline chloride, water and cerium, terbium, erbium chlorides, has been studied. It is established, that solubility isotherms of all the systems, testify to the formation of new solid phases of the composition: Ce(Tb, Er)xCl 3 x2C 5 H 14 ONClx3H 2 O. Individuality of new solid phases is proved by DTA method, the composition is confirmed by chemical analysis and data of PMR spectra, for choline chloride and its complexes with rare earth chlorides of the given composition PMR and IR spectra are studied

  20. Molecular Effects of Doxorubicin on Choline Metabolism in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Menglin Cheng

    2017-08-01

    Full Text Available Abnormal choline phospholipid metabolism is a hallmark of cancer. The magnetic resonance spectroscopy (MRS detected total choline (tCho signal can serve as an early noninvasive imaging biomarker of chemotherapy response in breast cancer. We have quantified the individual components of the tCho signal, glycerophosphocholine (GPC, phosphocholine (PC and free choline (Cho, before and after treatment with the commonly used chemotherapeutic drug doxorubicin in weakly metastatic human MCF7 and triple-negative human MDA-MB-231 breast cancer cells. While the tCho concentration did not change following doxorubicin treatment, GPC significantly increased and PC decreased. Of the two phosphatidylcholine-specific PLD enzymes, only PLD1, but not PLD2, mRNA was down-regulated by doxorubicin treatment. For the two reported genes encoding GPC phosphodiesterase, the mRNA of GDPD6, but not GDPD5, decreased following doxorubicin treatment. mRNA levels of choline kinase α (ChKα, which converts Cho to PC, were reduced following doxorubicin treatment. PLD1 and ChKα protein levels decreased following doxorubicin treatment in a concentration dependent manner. Treatment with the PLD1 specific inhibitor VU0155069 sensitized MCF7 and MDA-MB-231 breast cancer cells to doxorubicin-induced cytotoxicity. Low concentrations of 100 nM of doxorubicin increased MDA-MB-231 cell migration. GDPD6, but not PLD1 or ChKα, silencing by siRNA abolished doxorubicin-induced breast cancer cell migration. Doxorubicin induced GPC increase and PC decrease are caused by reductions in PLD1, GDPD6, and ChKα mRNA and protein expression. We have shown that silencing or inhibiting these genes/proteins can promote drug effectiveness and reduce adverse drug effects. Our findings emphasize the importance of detecting PC and GPC individually.

  1. Gold nanoparticle–choline complexes can block nicotinic acetylcholine receptors

    Directory of Open Access Journals (Sweden)

    Chur Chin

    2010-04-01

    Full Text Available Chur Chin1, In Kyeom Kim2, Dong Yoon Lim3, Ki Suk Kim4, Hyang Ae Lee4, Eun Joo Kim41Department of Pediatrics, Fatima Hospital, Daegu, Korea; 2Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Korea; 3Department of Pharmacology, School of Medicine, Chosun University, Gwangju, Korea; 4Korea Institute of Toxicology, Daejeon, KoreaAbstract: We identified a novel class of direct ion-channel blockers of ligand-gated ion channels called the gold nanoparticle–choline complex. Negatively charged gold nanoparticles (1.4 nm block ion pores by binding to the sulfur group of the cysteine loop of nicotinic acetylcholine receptors (nAChRs, and currents evoked by acetylcholine (Ach can break these bonds. The current evoked by ACh in nAChRs was blocked directly in ion pores by the gold nanoparticle–choline complex. In adrenal-gland perfusion studies, the complex also blocked nAChRs by diminishing catecholamine release by about 75%. An in vivo study showed muscle relaxation in rats after injection of the complex. These results will foster the application of gold nanoparticles as a direct ion-channel blocker. Keywords: negatively charged gold nanoparticle, choline, gold–sulfur bond, nicotinic acetylcholine receptor, direct ion-channel blocker

  2. Choline concentrations are lower in postnatal plasma of preterm infants than in cord plasma.

    Science.gov (United States)

    Bernhard, Wolfgang; Raith, Marco; Kunze, Rebecca; Koch, Vera; Heni, Martin; Maas, Christoph; Abele, Harald; Poets, Christian F; Franz, Axel R

    2015-08-01

    Choline is essential to human development, particularly of the brain in the form of phosphatidylcholine, sphingomyelin and acetylcholine, for bile and lipoprotein formation, and as a methyl group donator. Choline is actively transported into the fetus, and maternal supply correlates with cognitive outcome. Interruption of placental supply may therefore impair choline homeostasis in preterm infants. Determination of postnatal plasma concentrations of choline and its derivatives betaine and dimethylglycine (DMG) in preterm infants compared to cord and maternal blood matched for postmenstrual age (PMA). We collected plasma of very low-birth-weight infants undergoing neonatal intensive care (n = 162), cord plasma of term and preterm infants (n = 176, 24-42-week PMA), serum of parturients (n = 36), and plasma of healthy premenopausal women (n = 40). Target metabolites were analyzed with tandem mass spectrometry and reported as median (25th/75th percentiles). Cord plasma choline concentration was 41.4 (31.8-51.2) µmol/L and inversely correlated with PMA. In term but not in preterm infants, cord plasma choline was lower in girls than in boys. Prenatal glucocorticoid treatment did not affect choline levels in cord plasma, whereas betaine was decreased and DMG increased. In parturients and non-pregnant women, choline concentrations were 14.1 (10.3-16.9) and 8.8 (5.7-11.2) µmol/L, respectively, whereas betaine was lowest in parturients. After delivery, preterm infant plasma choline decreased to 20.8 (16.0-27.6) µmol/L within 48 h. Betaine and DMG correlated with plasma choline in all groups. In preterm infants, plasma choline decreases to 50 % of cord plasma concentrations, reflecting choline undernourishment and postnatal metabolic adaptation, and potentially contributing to impaired outcome.

  3. Choline-mediated modulation of hippocampal sharp wave-ripple complexes in vitro.

    Science.gov (United States)

    Fischer, Viktoria; Both, Martin; Draguhn, Andreas; Egorov, Alexei V

    2014-06-01

    The cholinergic system is critically involved in the modulation of cognitive functions, including learning and memory. Acetylcholine acts through muscarinic (mAChRs) and nicotinic receptors (nAChRs), which are both abundantly expressed in the hippocampus. Previous evidence indicates that choline, the precursor and degradation product of Acetylcholine, can itself activate nAChRs and thereby affects intrinsic and synaptic neuronal functions. Here, we asked whether the cellular actions of choline directly affect hippocampal network activity. Using mouse hippocampal slices we found that choline efficiently suppresses spontaneously occurring sharp wave-ripple complexes (SPW-R) and can induce gamma oscillations. In addition, choline reduces synaptic transmission between hippocampal subfields CA3 and CA1. Surprisingly, these effects are mediated by activation of both mAChRs and α7-containing nAChRs. Most nicotinic effects became only apparent after local, fast application of choline, indicating rapid desensitization kinetics of nAChRs. Effects were still present following block of choline uptake and are, therefore, likely because of direct actions of choline at the respective receptors. Together, choline turns out to be a potent regulator of patterned network activity within the hippocampus. These actions may be of importance for understanding state transitions in normal and pathologically altered neuronal networks. In this study we asked whether choline, the precursor and degradation product of acetylcholine, directly affects hippocampal network activity. Using mouse hippocampal slices we found that choline efficiently suppresses spontaneously occurring sharp wave-ripple complexes (SPW-R). In addition, choline reduces synaptic transmission between hippocampal subfields. These effects are mediated by direct activation of muscarinic as well as nicotinic cholinergic pathways. Together, choline turns out to be a potent regulator of patterned activity within hippocampal

  4. Rumen-protected choline: A significance effect on dairy cattle nutrition.

    Science.gov (United States)

    Jayaprakash, G; Sathiyabarathi, M; Robert, M Arokia; Tamilmani, T

    2016-08-01

    Choline is a vitamin-like substance it has multi-function in animal production, reproduction, and health. The transition period is most crucial stage in lactation cycle of dairy cows due to its association with negative hormonal and energy balances. Unfortunately, unprotected choline easily degrades in the rumen; therefore, choline added to the diet in a rumen-protected form. The use of rumen-protected choline (RPC) is a preventive measurement for the fatty liver syndrome and ketosis; may improve milk production as well as milk composition and reproduction parameters. This review summarizes the effectiveness of RPC on animal production, health, and reproduction.

  5. Phospholipid biosynthesis in Candida albicans: Regulation by the precursors inositol and choline

    International Nuclear Information System (INIS)

    Klig, L.S.; Friedli, L.; Schmid, E.

    1990-01-01

    Phospholipid metabolism in the pathogenic fungus Candida albicans was examined. The phospholipid biosynthetic pathways of C. albicans were elucidated and were shown to be similar to those of Saccharomyces cerevisiae. However, marked differences were seen between these two fungi in the regulation of the pathways in response to exogenously provided precursors inositol and choline. In S. cerevisiae, the biosynthesis of phosphatidylcholine via methylation of phosphatidylethanolamine appears to be regulated in response to inositol and choline; provision of choline alone does not repress the activity of this pathway. The same pathway in C. albicans responds to the exogenous provision of choline. Possible explanations for the observed differences in regulation are discussed

  6. Anaerobic choline metabolism in microcompartments promotes growth and swarming of Proteus mirabilis.

    Science.gov (United States)

    Jameson, Eleanor; Fu, Tiantian; Brown, Ian R; Paszkiewicz, Konrad; Purdy, Kevin J; Frank, Stefanie; Chen, Yin

    2016-09-01

    Gammaproteobacteria are important gut microbes but only persist at low levels in the healthy gut. The ecology of Gammaproteobacteria in the gut environment is poorly understood. Here, we demonstrate that choline is an important growth substrate for representatives of Gammaproteobacteria. Using Proteus mirabilis as a model, we investigate the role of choline metabolism and demonstrate that the cutC gene, encoding a choline-trimethylamine lyase, is essential for choline degradation to trimethylamine by targeted mutagenesis of cutC and subsequent complementation experiments. Proteus mirabilis can rapidly utilize choline to enhance growth rate and cell yield in broth culture. Importantly, choline also enhances swarming-associated colony expansion of P. mirabilis under anaerobic conditions on a solid surface. Comparative transcriptomics demonstrated that choline not only induces choline-trimethylamine lyase but also genes encoding shell proteins for the formation of bacterial microcompartments. Subsequent analyses by transmission electron microscopy confirmed the presence of such novel microcompartments in cells cultivated in liquid broth and hyper-flagellated swarmer cells from solid medium. Together, our study reveals choline metabolism as an adaptation strategy for P. mirabilis and contributes to better understand the ecology of this bacterium in health and disease. © 2015 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

  7. {sup 18}F-Choline, {sup 11}C-choline and {sup 11}C-acetate PET/CT: comparative analysis for imaging prostate cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Brogsitter, Claudia; Zoephel, Klaus; Kotzerke, Joerg [Carl Gustav Carus Medical School, University of Dresden, Department of Nuclear Medicine, Dresden (Germany)

    2013-07-15

    Prostate cancer (PCA) is the second most common tumour in men worldwide. Whereas prostate specific antigen (PSA) is an established biochemical marker, the optimal imaging method for all clinical scenarios has not yet been found. With the rising number of PET centres there is an increasing availability and use of {sup 18}F-/{sup 11}C-choline or {sup 11}C-acetate for staging of PCA. However, to date no final conclusion has been reached as to whether acetate or choline tracers should be preferred. In this review we provide an overview of the performance of choline and acetate PET for staging the primary and recurrent disease and lymph nodes in PCA, based on the literature of the last 10 years. Although predominantly choline has been used rather than acetate, both tracers performed in a similar manner in published studies. Choline as well as acetate have insufficient diagnostic accuracy for the staging of the primary tumour, due to a minimum detectable tumour size of 5 mm and inability to differentiate PCA from benign prostate hyperplasia, chronic prostatitis and high-grade intraepithelial neoplasia. Regarding lymph node staging, choline tracers have demonstrated a high specificity. Unfortunately, the sensitivity is only moderate. For staging recurrent disease, sensitivity depends on the level of serum PSA (PSA should be >2 ng/ml). This applies to both choline and acetate. However, despite these limitations, a significant number of patients with recurrent disease can benefit from PET imaging by a change in treatment planning. (orig.)

  8. Are dietary choline and betaine intakes determinants of total homocysteine concentration?

    Science.gov (United States)

    Elevated homocysteine concentrations are associated with an increased risk of cardiovascular disease and a decline in cognitive function. Intakes of choline and betaine, as methyl donors, may affect homocysteine concentrations. The objective was to examine whether choline and betaine intakes, assess...

  9. Dietary restriction of choline reduces hippocampal acetylcholine release in rats: in vivo microdialysis study.

    Science.gov (United States)

    Nakamura, A; Suzuki, Y; Umegaki, H; Ikari, H; Tajima, T; Endo, H; Iguchi, A

    2001-12-01

    We fed rats with a diet deficient in choline for 12 weeks and studied how dietary choline deficiency affected their behavior and their ability to release acetylcholine in discrete regions of rat brain using step-through passive avoidance task and in vivo microdialysis. In comparison with the control, rats fed the choline-deficient diet showed poorer retention of nociceptive memory in the passive avoidance task. Average choline level in cerebrospinal fluid in the choline-deficient group was significantly less (33.1%) than that of control rats. In vivo microdialysis showed no difference in the pattern of acetylcholine release enhanced by intraperitoneal administration of scopolamine hydrochloride (2 mg/kg) in the striatum between the two groups, whereas in the hippocampus, the maximum and subsequent increase of acetylcholine from the baseline by scopolamine injection was significantly lower in the choline-deficient group than in the control. From the results of our study, we speculate that long-term dietary restriction of choline can affect extra- and intracellular sources of substrates required for acetylcholine synthesis, and eventually limit the ability to release acetylcholine in the hippocampus. Reduced capacity to release acetylcholine in the hippocampus implies that the mechanism, maintaining acetylcholine synthesis on increased neuronal demand, may vary in discrete regions of the brain in response to dietary manipulation. The vulnerability of the mechanism in the hippocampus to dietary choline restriction is indicated by impaired mnemonic performance we observed.

  10. No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults

    NARCIS (Netherlands)

    Lippelt, Dominique; van der Kint, Sander; van Herk, Kevin; Naber, M.

    2016-01-01

    Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory

  11. Choline evokes fluid secretion by perfused rat mandibular gland without desensitization

    DEFF Research Database (Denmark)

    Murakami, M; Novak, I; Young, J A

    1986-01-01

    M and evoked secretory responses comparable with those of acetylcholine (0.05-1.0 microM) administered at similar Na concentrations. Continuous infusion of choline, in contrast to acetylcholine, did not lead to a fall off in the secretory response (desensitization or tachyphylaxis) until the choline...

  12. Umbilical choline and related methylamines betaine and dimethylglycine in relation to birth weight

    NARCIS (Netherlands)

    Hogeveen, M.; Heijer, M. den; Semmekrot, B.A.; Sporken, J.M.J.; Ueland, P.M.; Blom, H.J.

    2013-01-01

    Background:Low birth weight (LBW) is associated with increased morbidity and mortality for the newborn and risk of chronic disease in adulthood. Choline plays an essential role in the integrity of cell membranes, methylation reactions, and memory development. We examined whether choline, betaine,

  13. Conductivity and electrochemical stability of concentrated aqueous choline chloride solutions

    Science.gov (United States)

    Grishina, E. P.; Kudryakova, N. O.

    2017-10-01

    The conductivity and electrochemical stability of choline chloride (ChCl) solutions with water contents ranging from 20 to 39 wt % are studied. Exposing ChCl to moist ambient air yields a highly concentrated aqueous solution that, as an electrolyte, exhibits the properties and variations in conductivity with temperature and concentration characteristic of other similar systems. Its electrochemical stability window, determined by cyclic voltammetry, is comparable to that of ChCl-based deep eutectic solvents (DESs). Products of the electrolysis of ChCl‒H2O mixtures seem to be less toxic than those of Reline, Ethaline, and Maline.

  14. Carbon Nanotubes/Gold Nanoparticles Composite Film for the Construction of a Novel Amperometric Choline Biosensor

    Directory of Open Access Journals (Sweden)

    Baoyan Wu

    2011-01-01

    Full Text Available This study develops a facile method to fabricate a novel choline biosensor based on multiwalled carbon nanotubes (MWCNTs and gold nanoparticles (AuNPs. Chitosan, a natural biocompatible polymer, was used to solubilize MWCNTs for constructing the aqueous Chit-MWCNTs solution. Then Chit-MWCNTs were first dropped on the surface of a cleaned platinum electrode. Finally, a thiolated silica sol containing AuNPs and choline oxidase (ChOx was immobilized on the surface of the Chit-MWCNTs-modified electrode. The MWCNTs/AuNPs/Pt electrode showed excellent electrocatalytic activity for choline. The resulting choline biosensor showed high sensitivity of choline (3.56 μA/mM, and wide linear range from 0.05 to 0.8 mM with the detection limit of 15 μM. In addition, good reproducibility and stability were obtained.

  15. Choline Alleviates Parenteral Nutrition-Associated Duodenal Motility Disorder in Infant Rats.

    Science.gov (United States)

    Zhu, Jie; Wu, Yang; Guo, Yonggao; Tang, Qingya; Lu, Ting; Cai, Wei; Huang, Haiyan

    2016-09-01

    Parenteral nutrition (PN) has been found to influence duodenal motility in animals. Choline is an essential nutrient, and its deficiency is related to PN-associated organ diseases. Therefore, this study was aimed to investigate the role of choline supplementation in an infant rat model of PN-associated duodenal motility disorder. Three-week-old Sprague-Dawley male rats were fed chow and water (controls), PN solution (PN), or PN plus intravenous choline (600 mg/kg) (PN + choline). Rats underwent jugular vein cannulation for infusion of PN solution or 0.9% saline (controls) for 7 days. Duodenal oxidative stress status, concentrations of plasma choline, phosphocholine, and betaine and serum tumor necrosis factor (TNF)-α were assayed. The messenger RNA (mRNA) and protein expression of c-Kit proto-oncogene protein (c-Kit) and membrane-bound stem cell factor (mSCF) together with the electrophysiological features of slow waves in the duodenum were also evaluated. Rats on PN showed increased reactive oxygen species; decreased total antioxidant capacity in the duodenum; reduced plasma choline, phosphocholine, and betaine; and enhanced serum TNF-α concentrations, which were reversed by choline intervention. In addition, PN reduced mRNA and protein expression of mSCF and c-Kit, which were inversed under choline administration. Moreover, choline attenuated depolarized resting membrane potential and declined the frequency and amplitude of slow waves in duodenal smooth muscles of infant rats induced by PN, respectively. The addition of choline to PN may alleviate the progression of duodenal motor disorder through protecting smooth muscle cells from injury, promoting mSCF/c-Kit signaling, and attenuating impairment of interstitial cells of Cajal in the duodenum during PN feeding. © 2015 American Society for Parenteral and Enteral Nutrition.

  16. Role of choline PET/CT in guiding target volume delineation for irradiation of prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schwarzenboeck, S.M.; Kurth, J. [University Medical Centre Rostock, Department of Nuclear Medicine, Rostock (Germany); Gocke, C.; Kuhnt, T.; Hildebrandt, G. [University Medical Centre Rostock, Department of Radiotherapy, Rostock (Germany); Krause, B.J. [University Medical Centre Rostock, Department of Nuclear Medicine, Rostock (Germany); Universitaet Rostock, Department of Nuclear Medicine, Universitaetsmedizin Rostock, Rostock (Germany)

    2013-07-15

    Choline PET/CT has shown limitations for the detection of primary prostate cancer and nodal metastatic disease, mainly due to limited sensitivity and specificity. Conversely in the restaging of prostate cancer recurrence, choline PET/CT is a promising imaging modality for the detection of local regional and nodal recurrence with an impact on therapy management. This review highlights current literature on choline PET/CT for radiation treatment planning in primary and recurrent prostate cancer. Due to limited sensitivity and specificity in differentiating between benign and malignant prostatic tissues in primary prostate cancer, there is little enthusiasm for target volume delineation based on choline PET/CT. Irradiation planning for the treatment of single lymph node metastases on the basis of choline PET/CT is controversial due to its limited lesion-based sensitivity in primary nodal staging. In high-risk prostate cancer, choline PET/CT might diagnose lymph node metastases, which potentially can be included in the conventional irradiation field. Prior to radiation treatment of recurrent prostate cancer, choline PET/CT may prove useful for patient stratification by excluding distant disease which would require systemic therapy. In patients with local recurrence, choline PET/CT can be used to delineate local sites of recurrence within the prostatic resection bed allowing a boost to PET-positive sites. In patients with lymph node metastases outside the prostatic fossa and regional metastatic lymph nodes, choline PET/CT might influence radiation treatment planning by enabling extension of the target volume to lymphatic drainage sites with or without a boost to PET-positive lymph nodes. Further clinical randomized trials are required to assess treatment outcomes following choline-based biological radiation treatment planning in comparison with conventional radiation treatment planning. (orig.)

  17. Feeding a diet devoid of choline to lactating rodents restricts growth and lymphocyte development in offspring.

    Science.gov (United States)

    Lewis, E D; Goruk, S; Richard, C; Dellschaft, N S; Curtis, J M; Jacobs, R L; Field, C J

    2016-09-01

    The nutrient choline is necessary for membrane synthesis and methyl donation, with increased requirements during lactation. The majority of immune development occurs postnatally, but the importance of choline supply for immune development during this critical period is unknown. The objective of this study was to determine the importance of maternal supply of choline during suckling on immune function in their offspring among rodents. At parturition, Sprague-Dawley dams were randomised to either a choline-devoid (ChD; n 7) or choline-sufficient (ChS, 1 g/kg choline; n 10) diet with their offspring euthanised at 3 weeks of age. In a second experiment, offspring were weaned to a ChS diet until 10 weeks of age (ChD-ChS, n 5 and ChS-ChS, n 9). Splenocytes were isolated, and parameters of immune function were measured. The ChD offspring received less choline in breast milk and had lower final body and organ weight compared with ChS offspring (P<0·05), but this effect disappeared by week 10 with choline supplementation from weaning. ChD offspring had a higher proportion of T cells expressing activation markers (CD71 or CD28) and a lower proportion of total B cells (CD45RA+) and responded less to T cell stimulation (lower stimulation index and less IFN-γ production) ex vivo (P<0·05). ChD-ChS offspring had a lower proportion of total and activated CD4+ T cells, and produced less IL-6 after mitogen stimulation compared with cells from ChS-ChS (P<0·05). Our study suggests that choline is required in the suckling diet to facilitate immune development, and choline deprivation during this critical period has lasting effects on T cell function later in life.

  18. Choline and betaine intake and colorectal cancer risk in Chinese population: a case-control study.

    Science.gov (United States)

    Lu, Min-Shan; Fang, Yu-Jing; Pan, Zhi-Zhong; Zhong, Xiao; Zheng, Mei-Chun; Chen, Yu-Ming; Zhang, Cai-Xia

    2015-01-01

    Few studies have examined the association of choline and betaine intake with colorectal cancer risk, although they might play an important role in colorectal cancer development because of their role as methyl donors. The aim of this study was to examine the relationship between consumption of choline and betaine and colorectal cancer risk in a Chinese population. A case-control study was conducted between July 2010 and December 2013 in Guangzhou, China. Eight hundred and ninety consecutively recruited colorectal cancer cases were frequency matched to 890 controls by age (5-year interval) and sex. Dietary information was assessed with a validated food frequency questionnaire by face-to-face interviews. The logistic regression model was used to estimate multivariate odds ratios (ORs) and 95% confidence intervals (CIs). Total choline intake was inversely associated with colorectal cancer risk after adjustment for various lifestyle and dietary factors. The multivariate-adjusted OR was 0.54 (95%CI = 0.37-0.80, Ptrend colorectal cancer risk was associated with higher intakes of choline from phosphatidylcholine, glycerophosphocholine and sphingomyelin but not for free choline and phosphocholine. The inverse association of total choline intake with colorectal cancer risk was observed in both men and women, colon and rectal cancer. These inverse associations were not modified by folate intake. These results indicate that high intake of total choline is associated with a lower risk of colorectal cancer.

  19. Prenatal choline supplementation mitigates behavioral alterations associated with prenatal alcohol exposure in rats.

    Science.gov (United States)

    Thomas, Jennifer D; Idrus, Nirelia M; Monk, Bradley R; Dominguez, Hector D

    2010-10-01

    Prenatal alcohol exposure can alter physical and behavioral development, leading to a range of fetal alcohol spectrum disorders. Despite warning labels, pregnant women continue to drink alcohol, creating a need to identify effective interventions to reduce the severity of alcohol's teratogenic effects. Choline is an essential nutrient that influences brain and behavioral development. Recent studies indicate that choline supplementation can reduce the teratogenic effects of developmental alcohol exposure. The present study examined whether choline supplementation during prenatal ethanol treatment could mitigate the adverse effects of ethanol on behavioral development. Pregnant Sprague-Dawley rats were intubated with 6 g/kg/day ethanol in a binge-like manner from gestational days 5-20; pair-fed and ad libitum chow controls were included. During treatment, subjects from each group were intubated with either 250 mg/kg/day choline chloride or vehicle. Spontaneous alternation, parallel bar motor coordination, Morris water maze, and spatial working memory were assessed in male and female offspring. Subjects prenatally exposed to alcohol exhibited delayed development of spontaneous alternation behavior and deficits on the working memory version of the Morris water maze during adulthood, effects that were mitigated with prenatal choline supplementation. Neither alcohol nor choline influenced performance on the motor coordination task. These data indicate that choline supplementation during prenatal alcohol exposure may reduce the severity of fetal alcohol effects, particularly on alterations in tasks that require behavioral flexibility. These findings have important implications for children of women who drink alcohol during pregnancy. © 2010 Wiley-Liss, Inc.

  20. Intestinal absorption of cytidine diphosphate choline and its changes in the digestive tract

    International Nuclear Information System (INIS)

    Yashima, Keisuke; Takamatsu, Masatoshi; Okuda, Kunio

    1975-01-01

    Intestinal absorption of cytidine diphosphate choline (CDP-choline), its structural changes in the digestive tract, and hepatic uptake have been investigated in rats using 14 C-labeled ( 14 CH 3 attached to N of choline) and 3 H-labeled (at C 5 of pyrimidine) compounds. The results indicate that: 1) CDP-choline is relatively stable in the stomach, but is quickly degraded into cytidine and choline in the intestine; 2) The hepatic uptakes of 14 C and 3 H reach the maximum in two to three hours after oral administration; 3) Whereas the amount of 14 C remaining in the gut is inversely related to the hepatic uptake, no similar correlation is seen with 3 H-labeled CDP-choline, and 4) Extrahepatic uptake of 14 C and 3 H is very small. The possibility of phosphorylation in the mucosa of choline and cytidine has been discussed, based on the differences in relative amount of radioactivity in individual broken-down products in the intestinal lumen and mucosa. (auth.)

  1. Dietary Intake and Plasma Levels of Choline and Betaine in Children with Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Joanna C. Hamlin

    2013-01-01

    Full Text Available Abnormalities in folate-dependent one-carbon metabolism have been reported in many children with autism. Because inadequate choline and betaine can negatively affect folate metabolism and in turn downstream methylation and antioxidant capacity, we sought to determine whether dietary intake of choline and betaine in children with autism was adequate to meet nutritional needs based on national recommendations. Three-day food records were analyzed for 288 children with autism (ASDs who participated in the national Autism Intervention Research Network for Physical Health (AIR-P Study on Diet and Nutrition in children with autism. Plasma concentrations of choline and betaine were measured in a subgroup of 35 children with ASDs and 32 age-matched control children. The results indicated that 60–93% of children with ASDs were consuming less than the recommended Adequate Intake (AI for choline. Strong positive correlations were found between dietary intake and plasma concentrations of choline and betaine in autistic children as well as lower plasma concentrations compared to the control group. We conclude that choline and betaine intake is inadequate in a significant subgroup of children with ASDs and is reflected in lower plasma levels. Inadequate intake of choline and betaine may contribute to the metabolic abnormalities observed in many children with autism and warrants attention in nutritional counseling.

  2. Behavioural effects of chronic manipulations of dietary choline in senescent rats.

    Science.gov (United States)

    Fundaro, A; Paschero, A

    1990-01-01

    1. Senescent rats were maintained on choline-deficient and choline-enriched diets. The modifications in rat behaviour caused by the chronic manipulations of dietary choline were studied in two schedules of operant conditioning. 2. In the "periodic conditioning" test, the schedule of reinforcement, in a 100 min trial, was changed from a fixed ratio to a fixed interval schedule. In the "reversal" test the contingency for food delivery was switched four times from one lever to the other in a two lever Skinner box. 3. In the "periodic conditioning" test, the choline enriched group (430 mg/Kg/day) showed the same reduction of responses/reinforcement as controls, from the beginning to the end of trial; in the same group the time course reduction of responses/reinforcement became significant earlier than in the control group. The deficient-choline group in the last 40 min of "periodic conditioning" trial gave a reduction of responses/reinforcement greater than controls and one rat in the group did not learn the change of experimental schedule and extinguished its operant behaviour. 4. In the "reversal" test, the choline-enriched diet (320 mg/Kg/day) improved the reinforced responses in the IV reversal; one rat of the deficient-choline group could not learn the new operant schedule since the first reversal and continued to respond on the same lever during the whole of the test.

  3. Comparison of the computational NMR chemical shifts of choline with the experimental data

    International Nuclear Information System (INIS)

    Alcorn, C; Cuperlovic-Culf, M; Ghandi, K

    2012-01-01

    One of the main biological markers of the presence of cancer in living patients is an over-expression of total choline (tCho), which is the sum of free choline and its derivatives. 1 H Magnetic Resonance Spectroscopy, or H-MRS, enables the quantification of tCho via its proton spectra, and thus has the potential to be a diagnostic tool for the presence of cancer and an accurate early indicator of the response of cancer to treatment. However, it remains difficult to quantify individual choline derivatives, since they share a large structural similarity ((CH 3 ) 3 -N + -CH 2 -CH 2 -O-), of which the strongest signal detectable by MRS is that of the choline h ead group : the three methyl groups bonded to the nitrogen. This work used ACENet, a high performance computing system, to attempt to model the NMR parameters of choline derivatives, with the focus of this report being free choline. Optimized structures were determined using Density Functional Theory and the B3LYP electron correlation functional. The Polarizable Continuum Model was used to evaluate solvent effects. The Gauge-Invariant Atomic Orbital method was found to be the superior method for calculating the NMR parameters of cholines.

  4. Synthesis of acetylcholine from choline derived from phosphatidylcholine in a human neuronal cell line

    International Nuclear Information System (INIS)

    Blusztajn, J.K.; Liscovitch, M.; Richardson, U.I.

    1987-01-01

    Cholinergic neurons are unique among cells since they alone utilize choline not only as a component of major membrane phospholipids, such as phosphatidylcholine (Ptd-Cho), but also as a precursor of their neurotransmitter acetylcholine (AcCho). It has been hypothesized that choline-phospholipids might serve as a storage pool of choline for AcCho synthesis. The selective vulnerability of cholinergic neurons in certain neurodegenerative diseases (e.g., Alzheimer disease, motor neuron disorders) might result from the abnormally accelerated liberation of choline (to be used a precursor of AcCho) from membrane phospholipids, resulting in altered membrane composition and function and compromised neuronal viability. However, the proposed metabolic link between membrane turnover and AcCho synthesis has been difficult to demonstrate because of the heterogeneity of the preparations used. Here the authors used a population of purely cholinergic cells (human neuroblastomas, LA-N-2), incubated in the presence of [methyl- 3 H]methionine to selectively label PtdCho synthesized by methylation of phosphatidylethanolamine, the only pathway of de novo choline synthesis. Three peaks of radioactive material that cochromatographed with authentic AcCho, choline, and phosphocholine were observed when the water-soluble metabolites of the [ 3 H]PtdCho were purified by high-performance liquid chromatography. The results demonstrate that AcCho can be synthesized from choline derived from the degradation of endogenous PtdCho formed de novo by methylation of phosphatidylethanolamine

  5. No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults.

    Science.gov (United States)

    Lippelt, D P; van der Kint, S; van Herk, K; Naber, M

    2016-01-01

    Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory in healthy, young students one to two hours after supplementation. In experiment 1, 28 participants performed a visuospatial working memory task. In experiment 2, 26 participants performed a declarative picture memorization task. In experiment 3, 40 participants performed a verbal working memory task in addition to the visuospatial working memory and declarative picture task. All tasks were conducted approximately 60 minutes after the ingestion of 2.0-2.5g of either choline bitartrate or placebo. We found that choline did not significantly enhance memory performance during any of the tasks. The null hypothesis that choline does not improve memory performance as compared to placebo was strongly supported by Bayesian statistics. These results are in contrast with animal studies suggesting that choline supplementation boosts memory performance and learning. We conclude that choline likely has no acute effects on cholinergic memory functions in healthy human participants.

  6. Interaction between cytotoxic effects of γ-radiation and folate deficiency in relation to choline reserves

    International Nuclear Information System (INIS)

    Batra, Vipen; Devasagayam, Thomas Paul Asir

    2009-01-01

    The search for non-toxic radio-protective drugs has yielded many potential agents but most of these compounds have certain amount of toxicity. Recent studies have indicated that bio-molecules such as folate and choline might be of radio-protective value as they are, within broad dose ranges, non-toxic to humans and experimental animals. The objective of the present study was to investigate choline dependent adaptive response to potential synergistic cytotoxic effect of folate deficiency and γ-radiation. Male Swiss mice maintained on folate sufficient diet (FSD) and folate free diet (FFD) based on AIN-93 M formula, were subjected to 1-4 Gy total body γ-irradiation. To investigate liver DNA damage, apurinic/apyrimidinic sites (AP sites) were quantified. A significant increase in liver DNA AP sites with concomitant depletion of liver choline reserves was observed when γ-radiation was combined with folate deficiency. Further work in this direction suggested that cytotoxic interaction between folate deficiency and gamma radiation might induce utilization of choline and choline containing moieties by modifying levels of key regulatory enzymes dihydrofolate reductase (DHFR) and choline oxidase (ChoOx). Another major finding of these studies is that significant liver damage at higher doses of radiation (3-4 Gy), might release considerable amounts of choline reserves to serum. In conclusion, a plausible interpretation of the present studies is that folate deprivation and γ-radiation interact to mobilize additional choline reserves of hepatic tissue, for redistribution to other organs, which could not be utilized by folate deficiency alone. Present results clearly indicated a distinct choline pool in liver and kidney tissues that could be utilized by folate deficient animals only under radiation stress conditions

  7. Choline requirements of White Pekin ducks from hatch to 21 days of age.

    Science.gov (United States)

    Wen, Z G; Tang, J; Hou, S S; Guo, Y M; Huang, W; Xie, M

    2014-12-01

    A dose-response experiment with 8 dietary choline levels (302, 496, 778, 990, 1,182, 1,414, 1,625, and 1,832 mg/kg) was conducted with male White Pekin ducks to estimate the choline requirement from hatch to 21 d of age. Three hundred eighty-four 1-d-old male White Pekin ducks were randomly assigned to 8 dietary treatments, each containing 6 replicate pens with 8 birds per pen. At 21 d of age, weight gain, feed intake, and feed/gain from each pen were calculated for feeding period, and 2 ducks selected randomly from each pen were euthanized and the liver was collected to determine total lipids, triglycerides, and phospholipids. In our study, perosis, poor growth, and high liver fat were all observed in choline-deficient ducks and incidence of perosis was zero when dietary choline was 1,182 mg/kg. As dietary choline increased, the weight gain and feed intake increased linearly or quadratically (P < 0.05). On the other hand, as dietary choline increased, the total lipid and triglyceride in liver decreased linearly and liver phospholipid increased linearly (P < 0.05), and the lipotropic activity of choline may be associated with increasing phospholipid at a high dietary choline level. According to broken-line regression, the choline requirements for weight gain and feed intake were 810 and 823 mg/kg, respectively, but higher requirement should be considered to prevent perosis and excess liver lipid deposition completely. ©2014 Poultry Science Association Inc.

  8. Choline and betaine intake and colorectal cancer risk in Chinese population: a case-control study.

    Directory of Open Access Journals (Sweden)

    Min-Shan Lu

    Full Text Available Few studies have examined the association of choline and betaine intake with colorectal cancer risk, although they might play an important role in colorectal cancer development because of their role as methyl donors. The aim of this study was to examine the relationship between consumption of choline and betaine and colorectal cancer risk in a Chinese population.A case-control study was conducted between July 2010 and December 2013 in Guangzhou, China. Eight hundred and ninety consecutively recruited colorectal cancer cases were frequency matched to 890 controls by age (5-year interval and sex. Dietary information was assessed with a validated food frequency questionnaire by face-to-face interviews. The logistic regression model was used to estimate multivariate odds ratios (ORs and 95% confidence intervals (CIs. Total choline intake was inversely associated with colorectal cancer risk after adjustment for various lifestyle and dietary factors. The multivariate-adjusted OR was 0.54 (95%CI = 0.37-0.80, Ptrend <0.01 comparing the highest with the lowest quartile. No significant associations were observed for betaine or total choline+betaine intakes. For choline-containing compounds, lower colorectal cancer risk was associated with higher intakes of choline from phosphatidylcholine, glycerophosphocholine and sphingomyelin but not for free choline and phosphocholine. The inverse association of total choline intake with colorectal cancer risk was observed in both men and women, colon and rectal cancer. These inverse associations were not modified by folate intake.These results indicate that high intake of total choline is associated with a lower risk of colorectal cancer.

  9. Experience in using ceretone (choline alfoscerate in brain concussion

    Directory of Open Access Journals (Sweden)

    N G Voropay

    2010-01-01

    Full Text Available Nootropics are used to treat patients who have sustained concussion of the brain and complain of reductions in memory and working capacity, as well as emotional disorders. The efficacy of ceretone® (choline alfoscerate was studied in 76 patients (45 men and 31 women whose age was 21-56 years who had sustained brain concussion and had complaints of headache, easy fatigability, nocturnal sleep disorders, daytime sleepiness, anxiety, and bad mood. Thirty-nine patients received intravenous ceretone® in a dose of 1000 mg/day for 10 days; the other 37 patients formed a control group. A one-year follow-up indicated that ceretone® had a positive effect on health, autonomic, and emotional status and working capacity.

  10. Choline acetyltransferase-containing neurons in the human parietal neocortex

    Directory of Open Access Journals (Sweden)

    V Benagiano

    2009-06-01

    Full Text Available A number of immunocytochemical studies have indicated the presence of cholinergic neurons in the cerebral cortex of various species of mammals. Whether such cholinergic neurons in the human cerebral cortex are exclusively of subcortical origin is still debated. In this immunocytochemical study, the existence of cortical cholinergic neurons was investigated on surgical samples of human parietal association neocortex using a highly specific monoclonal antibody against choline acetyltransferase (ChAT, the acetylcholine biosynthesising enzyme. ChAT immunoreactivity was detected in a subpopulation of neurons located in layers II and III. These were small or medium-sized pyramidal neurons which showed cytoplasmic immunoreactivity in the perikarya and processes, often in close association to blood microvessels. This study, providing demonstration of ChAT neurons in the human parietal neocortex, strongly supports the existence of intrinsic cholinergic innervation of the human neocortex. It is likely that these neurons contribute to the cholinergic innervation of the intracortical microvessels.

  11. Choline-based biodegradable ionic liquid catalyst for Mannich-type

    Indian Academy of Sciences (India)

    Choline-based biodegradable ionic liquid catalyst for Mannich-type reaction ... Abstract. A three-component Mannich-type reaction of aromatic aldehydes, ketones, and amines was catalyzed by a novel ... Journal of Chemical Sciences | News.

  12. Bronsted acid-functionalized choline chloride-butane sultone for the ...

    Indian Academy of Sciences (India)

    M P PADMA PRIYA

    2018-03-21

    Mar 21, 2018 ... Choline chloride and 1,4-butane sultone were combined to obtain a sulphonic acid-functionalized ..... Knifton J F and Sanderson J R 1990 Method for produc- ... alkenes via the Knoevenagel condensation Tetrahedron. Lett.

  13. Loss of P53 Function in Colon Cancer Cells Results in Increased Phosphocholine and Total Choline

    Directory of Open Access Journals (Sweden)

    Noriko Mori

    2004-10-01

    Full Text Available Mutations in the p53 gene are the most frequently observed genetic lesions in human cancers. Human cancers that contain a p53 mutation are more aggressive, more apt to metastasize, and more often fatal. p53 controls numerous downstream targets that can influence various outcomes such as apoptosis, growth arrest, and DNA repair. Based on previous observations using 1H magnetic resonance spectroscopy (MRS, we have identified choline phospholipid metabolite intensities typical of increased malignancy. Here we have used 1H MRS to characterize the choline phospholipid metabolite levels of p53+/+ and p53−/– cells, and demonstrated that loss of p53 function results in increased phosphocholine and total choline. These data suggest that the increased malignancy of cancer cells resulting from loss of p53 may be mediated, in part, through the choline phospholipid pathway.

  14. Lewis acidic (choline chloride.3ZnCl2) ionic liquid: A green and ...

    Indian Academy of Sciences (India)

    Choline chloride; zinc chloride; ionic liquid; one-pot; triarylmethane. 1. Introduction ... applications such as zinc electroplating11 and batter- ies.12 It has also been used as ... as indicated by Thin Layer Chromatography (TLC), the catalyst was ...

  15. Lecithin: a by-product of biodiesel production and a source of choline for dairy cows

    Directory of Open Access Journals (Sweden)

    Igino Andrighetto

    2012-04-01

    Full Text Available The aim of the present study was to compare the effects of soy lecithins (L, a by-product of the biodiesel production process, and choline chloride microencapsulated with hydrogenated vegetable oils (C on dry matter intake, milk yield,  milk quality traits, milk choline and haematological profile of dairy cows. A total of 12 mid-lactating Holstein Friesian cows were assigned to one of two experimental groups and fed according to cross-over design (2 diets x 2 periods. Diets were isoenergetic, isofibrous and isonitrogenous and had the same content of choline. Dry matter intake was not affected by the diet, but L led to lower milk choline (P

  16. Choline metabolism as a basis for the selective vulnerability of cholinergic neurons

    Science.gov (United States)

    Wurtman, R. J.

    1992-01-01

    The unique propensity of cholinergic neurons to use choline for two purposes--ACh and membrane phosphatidylcholine synthesis--may contribute to their selective vulnerability in Alzheimer's disease and other cholinergic neurodegenerative disorders. When physiologically active, the neurons use free choline taken from the 'reservoir' in membrane phosphatidylcholine to synthesize ACh; this can lead to an actual decrease in the quantity of membrane per cell. Alzheimer's disease (but not Down's syndrome, or other neurodegenerative disorders) is associated with characteristic neurochemical lesions involving choline and ethanolamine: brain levels of these compounds are diminished, while those of glycerophosphocholine and glycerophosphoethanolamine (breakdown products of their respective membrane phosphatides) are increased, both in cholinergic and noncholinergic brain regions. Perhaps this metabolic disturbance and the tendency of cholinergic neurons to 'export' choline--in the form of ACh--underlie the selective vulnerability of the neurons. Resulting changes in membrane composition could abnormally expose intramembraneous proteins such as amyloid precursor protein to proteases.

  17. Serial plasma choline measurements after cardiac arrest in patients undergoing mild therapeutic hypothermia: a prospective observational pilot trial.

    Directory of Open Access Journals (Sweden)

    Christian Storm

    Full Text Available OBJECTIVE: Choline is related to phospholipid metabolism and is a marker for global ischaemia with a small reference range in healthy volunteers. The aim of our study was to characterize the early kinetics of plasma free choline in patients after cardiac arrest. Additionally, we investigated the potential of plasma free choline to predict neurological outcome. METHODS: Twenty patients admitted to our medical intensive care unit were included in this prospective, observational trial. All patients were enrolled between May 2010 and May 2011. They received post cardiac arrest treatment including mild therapeutic hypothermia which was initiated with a combination of cold fluid and a feedback surface cooling device according to current guidelines. Sixteen blood samples per patient were analysed for plasma free choline levels within the first week after resuscitation. Choline was detected by liquid chromatography-tandem mass spectrometry. RESULTS: Most patients showed elevated choline levels on admission (median 14.8 µmol/L; interquartile range; IQR 9.9-20.1 which subsequently decreased. 48 hours after cardiac arrest choline levels in all patients reached subnormal levels at a median of 4.0 µmol/L (IQR 3-4.9; p = 0.001. Subsequently, choline levels normalized within seven days. There was no significant difference in choline levels when groups were analyzed in relation to neurological outcome. CONCLUSIONS: Our data indicate a choline deficiency in the early postresucitation phase. This could potentially result in impaired cell membrane recovery. The detailed characterization of the early choline time course may aid in planning of choline supplementation trials. In a limited number of patients, choline was not promising as a biomarker for outcome prediction.

  18. Usual Choline Intakes Are Associated with Egg and Protein Food Consumption in the United States

    Directory of Open Access Journals (Sweden)

    Taylor C. Wallace

    2017-08-01

    Full Text Available Choline is an essential nutrient with critical roles in several biological processes including neuronal development, cell signaling, nerve impulse transmission, and lipid transport and metabolism. The National Cancer Institute method was used to assess usual intakes of choline from foods according to data for participants enrolled in the National Health and Nutrition Examination Survey 2009–2014 datasets and pregnant women in the 2005–2014 datasets. Suboptimal intakes of choline are present across many gender and life-stage subpopulations, as well as pregnant women in the U.S. Only 8.03 ± 0.56% of adults and 8.51 ± 2.89% pregnant women meet the AI for choline. Children 2–3 years were the most likely to meet their gender and life-stage specific AI, followed by children 4–8 years. Adults 19+ years who consume eggs were more likely to meet their gender and life-stage AI as compared to non-consumers (57.3 ± 1.45% and 2.43 ± 0.28%. Consumers of eggs had almost double the usual intake of choline as compared to non-consumers (525 ± 5.17 mg/d and 294 ± 1.98; p < 0.0001. Protein food (meat, poultry and seafood consumption also increased usual choline intakes compared to non-consumers (345 ± 2.21 mg/day and 235 ± 8.81; p < 0.0001 to a lesser degree, but did not result in substantial increases in the percent of individuals meeting the AI. No subpopulation exceeded the UL for choline. This research illustrates that it is extremely difficult to achieve the AI for choline without consuming eggs or taking a dietary supplement.

  19. Chronic choline supplementation improves cognitive and motor performance via modulating oxidative and neurochemical status in rats.

    Science.gov (United States)

    Tabassum, Saiqa; Haider, Saida; Ahmad, Saara; Madiha, Syeda; Parveen, Tahira

    2017-08-01

    Choline, an essential nutrient, accounts for multiple functions in the body and brain. While its beneficial effects on healthy adults are not clear, choline supplementation is important during pregnancy for brain development, in elderly patients for support of cognitive performance and in patients with neurological disorders to reduce memory deficits. Thus, the aim of this study is to investigate whether choline administration in healthy adult rats beneficially impacts cognitive and locomotor performance, and associated oxidative and neurochemical outcomes. Two groups, control and choline, received tap water and choline bitartrate, respectively at the dose equivalent to adequate intake for five weeks. Food intake and body weight were monitored daily. Behavioral analysis comprising assessment of cognitive performance (by novel object recognition, passive avoidance and Morris Water Maze test) and locomotor performance (by Open field, Kondziela's inverted screen and beam walking test) were performed. Following testing, rats were decapitated and brain samples were collected for estimation of acetylcholine, redox profile and monoamine measurements. The results showed that chronic choline administration significantly improves cognitive and locomotor performance accompanied by a reduction in oxidative stress, enhanced cholinergic neurotransmission and monoamine levels in the brain of healthy adult rats. Hence, chronic choline intake was found to improve behavioral, oxidative and neurochemical outcomes in the normal population, so it can be suggested that choline tablets can be used as a safe and effective supplement for improving the neurological health of normal individuals and that they might also be beneficial in preventing cognitive and motor disorders later in life. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Prenatal choline deficiency does not enhance hippocampal vulnerability after kainic acid-induced seizures in adulthood.

    Science.gov (United States)

    Wong-Goodrich, Sarah J E; Tognoni, Christina M; Mellott, Tiffany J; Glenn, Melissa J; Blusztajn, Jan K; Williams, Christina L

    2011-09-21

    Choline is a vital nutrient needed during early development for both humans and rodents. Severe dietary choline deficiency during pregnancy leads to birth defects, while more limited deficiency during mid- to late pregnancy causes deficits in hippocampal plasticity in adult rodent offspring that are accompanied by cognitive deficits only when task demands are high. Because prenatal choline supplementation confers neuroprotection of the adult hippocampus against a variety of neural insults and aids memory, we hypothesized that prenatal choline deficiency may enhance vulnerability to neural injury. To examine this, adult offspring of rat dams either fed a control diet (CON) or one deficient in choline (DEF) during embryonic days 12-17 were given multiple injections (i.p.) of saline (control) or kainic acid to induce seizures and were euthanized 16 days later. Perhaps somewhat surprisingly, DEF rats were not more susceptible to seizure induction and showed similar levels of seizure-induced hippocampal histopathology, GAD expression loss, upregulated hippocampal GFAP and growth factor expression, and increased dentate cell and neuronal proliferation as that seen in CON rats. Although prenatal choline deficiency compromises adult hippocampal plasticity in the intact brain, it does not appear to exacerbate the neuropathological response to seizures in the adult hippocampus at least shortly after excitotoxic injury. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Uptake of [N-Me-3H]-choline by synaptosomes from the central nervous system of Locusta migratoria

    International Nuclear Information System (INIS)

    Breer, H.

    1982-01-01

    The accumulation of 3H-choline by isolated synaptosomes from the central nervous system of locust was studied at concentrations varying from 0.05 to 40 microM. Kinetic analysis of the saturable process revealed a high-affinity and a low-affinity system. The high-affinity uptake was competitively inhibited by hemicholinium-3 and was absolutely dependent on external sodium. Elevated potassium concentrations inhibited choline uptake. The choline uptake by insect synaptosomes was found to be remarkably resistant to a variety of metabolic inhibitors. The reduced choline uptake under depolarizing conditions (high potassium concentration or veratridine) in the absence of calcium implies that electrochemical gradients are important for high-affinity choline uptake. Depolarization of preloaded synaptosomes under appropriate conditions resulted in a significant release of newly accumulated choline radioactivity

  2. Higher Dietary Choline and Betaine Intakes Are Associated with Better Body Composition in the Adult Population of Newfoundland, Canada.

    Directory of Open Access Journals (Sweden)

    Xiang Gao

    Full Text Available Choline is an essential nutrient and betaine is an osmolyte and methyl donor. Both are important to maintain health including adequate lipid metabolism. Supplementation of dietary choline and betaine increase muscle mass and reduce body fat in animals. However, little data is available regarding the role of dietary choline and betaine on body composition in humans.To investigate the association between dietary choline and betaine intakes with body composition in a large population based cross-sectional study.A total of 3214 subjects from the CODING (Complex Disease in Newfoundland population: Environment and Genetics study were assessed. Dietary choline and betaine intakes were computed from the Willett Food Frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry following a 12-hour fast. Major confounding factors including age, sex, total calorie intake and physical activity level were controlled in all analyses.Significantly inverse correlations were found between dietary choline and betaine intakes, with all obesity measurements: total percent body fat (%BF, percent trunk fat (%TF, percent android fat (%AF, percent gynoid fat (%GF and anthropometrics: weight, body mass index, waist circumference, waist-to-hip ratio in both women and men (r range from -0.13 to -0.47 for choline and -0.09 to -0.26 for betaine, p<0.001 for all. Dietary choline intake had stronger association than betaine. Moreover, obese subjects had the lowest dietary choline and betaine intakes, with overweight subjects in the middle, and normal weight subjects consumed the highest dietary choline and betaine (p<0.001. Vice versa, when subjects were ranked according to dietary choline and betaine intakes, subjects with the highest intake of both had the lowest %TF, %AF, %GF, %BF and highest %LM among the groups in both sexes.Our findings indicate that high dietary choline and betaine intakes are significantly associated with favorable body

  3. Choline kinase-alpha by regulating cell aggressiveness and drug sensitivity is a potential druggable target for ovarian cancer

    OpenAIRE

    Granata, A; Nicoletti, R; Tinaglia, V; De Cecco, L; Pisanu, M E; Ricci, A; Podo, F; Canevari, S; Iorio, E; Bagnoli, M; Mezzanzanica, D

    2013-01-01

    Background: Aberrant choline metabolism has been proposed as a novel cancer hallmark. We recently showed that epithelial ovarian cancer (EOC) possesses an altered MRS-choline profile, characterised by increased phosphocholine (PCho) content to which mainly contribute over-expression and activation of choline kinase-alpha (ChoK-alpha). Methods: To assess its biological relevance, ChoK-alpha expression was downmodulated by transient RNA interference in EOC in vitro models. Gene expression profi...

  4. Detection of choline transporter-like 1 protein CTL1 in neuroblastoma × glioma cells and in the CNS, and its role in choline uptake

    Czech Academy of Sciences Publication Activity Database

    Machová, Eva; O´Regan, S.; Newcombe, J.; Meunier, F. M.; Prentice, J.; Dove, R.; Lisá, Věra; Doležal, Vladimír

    2009-01-01

    Roč. 110, č. 4 (2009), s. 1297-1309 ISSN 0022-3042 R&D Projects: GA MŠk(CZ) LC554; GA AV ČR(CZ) IAA500110703 Institutional research plan: CEZ:AV0Z50110509 Keywords : CTL1 * choline * cell growth Subject RIV: ED - Physiology Impact factor: 3.999, year: 2009

  5. Choline transporter mutations in severe congenital myasthenic syndrome disrupt transporter localization.

    Science.gov (United States)

    Wang, Haicui; Salter, Claire G; Refai, Osama; Hardy, Holly; Barwick, Katy E S; Akpulat, Ugur; Kvarnung, Malin; Chioza, Barry A; Harlalka, Gaurav; Taylan, Fulya; Sejersen, Thomas; Wright, Jane; Zimmerman, Holly H; Karakaya, Mert; Stüve, Burkhardt; Weis, Joachim; Schara, Ulrike; Russell, Mark A; Abdul-Rahman, Omar A; Chilton, John; Blakely, Randy D; Baple, Emma L; Cirak, Sebahattin; Crosby, Andrew H

    2017-11-01

    The presynaptic, high-affinity choline transporter is a critical determinant of signalling by the neurotransmitter acetylcholine at both central and peripheral cholinergic synapses, including the neuromuscular junction. Here we describe an autosomal recessive presynaptic congenital myasthenic syndrome presenting with a broad clinical phenotype due to homozygous choline transporter missense mutations. The clinical phenotype ranges from the classical presentation of a congenital myasthenic syndrome in one patient (p.Pro210Leu), to severe neurodevelopmental delay with brain atrophy (p.Ser94Arg) and extend the clinical outcomes to a more severe spectrum with infantile lethality (p.Val112Glu). Cells transfected with mutant transporter construct revealed a virtually complete loss of transport activity that was paralleled by a reduction in transporter cell surface expression. Consistent with these findings, studies to determine the impact of gene mutations on the trafficking of the Caenorhabditis elegans choline transporter orthologue revealed deficits in transporter export to axons and nerve terminals. These findings contrast with our previous findings in autosomal dominant distal hereditary motor neuropathy of a dominant-negative frameshift mutation at the C-terminus of choline transporter that was associated with significantly reduced, but not completely abrogated choline transporter function. Together our findings define divergent neuropathological outcomes arising from different classes of choline transporter mutation with distinct disease processes and modes of inheritance. These findings underscore the essential role played by the choline transporter in sustaining acetylcholine neurotransmission at both central and neuromuscular synapses, with important implications for treatment and drug selection. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Evaluation of the PET component of simultaneous [18F]choline PET/MRI in prostate cancer: comparison with [18F]choline PET/CT

    International Nuclear Information System (INIS)

    Wetter, Axel; Lipponer, Christine; Nensa, Felix; Altenbernd, Jens-Christian; Schlosser, Thomas; Lauenstein, Thomas; Heusch, Philipp; Ruebben, Herbert; Bockisch, Andreas; Poeppel, Thorsten; Nagarajah, James

    2014-01-01

    The aim of this study was to evaluate the positron emission tomography (PET) component of [ 18 F]choline PET/MRI and compare it with the PET component of [ 18 F]choline PET/CT in patients with histologically proven prostate cancer and suspected recurrent prostate cancer. Thirty-six patients were examined with simultaneous [ 18 F]choline PET/MRI following combined [ 18 F]choline PET/CT. Fifty-eight PET-positive lesions in PET/CT and PET/MRI were evaluated by measuring the maximum and mean standardized uptake values (SUV max and SUV mean ) using volume of interest (VOI) analysis. A scoring system was applied to determine the quality of the PET images of both PET/CT and PET/MRI. Agreement between PET/CT and PET/MRI regarding SUV max and SUV mean was tested using Pearson's product-moment correlation and Bland-Altman analysis. All PET-positive lesions that were visible on PET/CT were also detectable on PET/MRI. The quality of the PET images was comparable in both groups. Median SUV max and SUV mean of all lesions were significantly lower in PET/MRI than in PET/CT (5.2 vs 6.1, p max of PET/CT and PET/MRI (R = 0.86, p mean of PET/CT and PET/MRI (R = 0.81, p max of PET/CT vs PET/MRI and -1.12 to +2.23 between SUV mean of PET/CT vs PET/MRI. PET image quality of PET/MRI was comparable to that of PET/CT. A highly significant correlation between SUV max and SUV mean was found. Both SUV max and SUV mean were significantly lower in [ 18 F]choline PET/MRI than in [ 18 F]choline PET/CT. Differences of SUV max and SUV mean might be caused by different techniques of attenuation correction. Furthermore, differences in biodistribution and biokinetics of [ 18 F]choline between the subsequent examinations and in the respective organ systems have to be taken into account. (orig.)

  7. Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure.

    Science.gov (United States)

    Balaraman, Sridevi; Idrus, Nirelia M; Miranda, Rajesh C; Thomas, Jennifer D

    2017-05-01

    Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol's developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation. To determine whether choline supplementation alters ethanol's long-lasting effects on miRNAs, Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol from postnatal days (PD) 4-9 via intubation; controls received sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) or saline vehicle subcutaneously (s.c.) from PD 4-21. On PD 22, subjects were sacrificed, and RNA was isolated from the hippocampus. MiRNA expression was assessed with TaqMan Human MicroRNA Panel Low-Density Arrays. Ethanol significantly increased miRNA expression variance, an effect that was attenuated with choline supplementation. Cluster analysis of stably expressed miRNAs that exceeded an ANOVA p < 0.05 criterion indicated that for both male and female offspring, control and ethanol-exposed groups were most dissimilar from each other, with choline-supplemented groups in between. MiRNAs that expressed an average 2-fold change due to ethanol exposure were further analyzed to identify which ethanol-sensitive miRNAs were protected by choline supplementation. We found that at a false discovery rate (FDR)-adjusted criterion of p < 0.05, miR-200c was induced by ethanol exposure and that choline prevented this effect. Collectively, our data show that choline supplementation can normalize disturbances in miRNA expression following developmental alcohol exposure and can protect specific miRNAs from induction by

  8. Effect of choline chloride supplementation on milk production and milk composition of Etawah grade goats

    Directory of Open Access Journals (Sweden)

    Supriyati

    2016-08-01

    Full Text Available Abstract Background The effect of choline chloride supplementation through forced drinking combined with concentrate diets containing Ca-fish oil on milk production and milk composition of Etawah Grade goats was evaluated. Choline chloride is an essential component in ruminant diets as it is required for fat metabolism. Method The experiment was conducted in a completely randomized block design with three types of treatments and eight replications. The trial had two successive experimental periods; the first, during the eight weeks of late pregnancy, and the second, during the first 12 weeks of lactation. Twenty-four Etawah Grade does in the second gestation period were divided into three treatment groups. Commercial choline chloride 60 % in corncobs-based powder was used as a source of choline chloride. The treatments were no supplementation (control and supplemented with either 4 g or 8 g/2days of choline chloride. Choline chloride was given to the animals through a forced drinking technique, after dissolving it in 60 ml drinking water. The initial body weight of does was 38.81 ± 3.66 kg. The does were penned individually, and were given fresh chopped King Grass ad libitum and 700 g/day of concentrate diets containing Ca-fish oil, starting eight weeks prior to expecting kidding and continuing for 12 weeks of parturition. Results All nutrient intakes were not significantly different (p > 0.05 among the treatments during the late pregnancy and the lactation periods. Supplementation did not affect (p > 0.05 the average daily gains and feed conversion ratio during pregnancy but gave effects (p < 0.05 on the average daily gains, feed conversion ratio and income over feed cost during lactation. The highest average daily milk yields and 4 % fat corrected milk yields were found in goats supplemented with 4 g/2days of choline chloride and increased by 17.00 % and 24.67 %, respectively, compared to the control. Moreover, milk

  9. Structure of choline oxidase in complex with the reaction product glycine betaine.

    Science.gov (United States)

    Salvi, Francesca; Wang, Yuan-Fang; Weber, Irene T; Gadda, Giovanni

    2014-02-01

    Choline oxidase from Arthrobacter globiformis, which is involved in the biosynthesis of glycine betaine from choline, has been extensively characterized in its mechanistic and structural properties. Despite the knowledge gained on the enzyme, the details of substrate access to the active site are not fully understood. The `loop-and-lid' mechanism described for the glucose-methanol-choline enzyme superfamily has not been confirmed for choline oxidase. Instead, a hydrophobic cluster on the solvent-accessible surface of the enzyme has been proposed by molecular dynamics to control substrate access to the active site. Here, the crystal structure of the enzyme was solved in complex with glycine betaine at pH 6.0 at 1.95 Å resolution, allowing a structural description of the ligand-enzyme interactions in the active site. This structure is the first of choline oxidase in complex with a physiologically relevant ligand. The protein structures with and without ligand are virtually identical, with the exception of a loop at the dimer interface, which assumes two distinct conformations. The different conformations of loop 250-255 define different accessibilities of the proposed active-site entrance delimited by the hydrophobic cluster on the other subunit of the dimer, suggesting a role in regulating substrate access to the active site.

  10. Enhancing the biodegradation of oil in sandy sediments with choline: A naturally methylated nitrogen compound

    International Nuclear Information System (INIS)

    Mortazavi, Behzad; Horel, Agota; Anders, Jennifer S.; Mirjafari, Arsalan; Beazley, Melanie J.; Sobecky, Patricia A.

    2013-01-01

    We investigated how additions of choline, a naturally occurring methylated nitrogen-containing compound, accelerated hydrocarbon degradation in sandy sediments contaminated with moderately weathered crude oil (4000 mg kg −1 sediment). Addition of lauroylcholine chloride (LCC) and tricholine citrate (TCC) to oil contaminated sediments resulted in 1.6 times higher hydrocarbon degradation rates compared to treatments without added choline derivatives. However, the degradation rate constant for the oil contaminated sediments amended with LCC was similar to that in contaminated sediments amended with inorganic nitrogen, phosphorus, and glucose. Additions of LLC and TCC to sediments containing extensively weathered oil also resulted in enhanced mineralization rates. Cultivation-free 16S rRNA analysis revealed the presence of an extant microbial community with clones closely related to known hydrocarbon degraders from the Gammaproteobacteria, Alphaproteobacteria, and Firmicutes phyla. The results demonstrate that the addition of minimal amounts of organic compounds to oil contaminated sediments enhances the degradation of hydrocarbons. -- Highlights: •Aerobic degradation of weathered crude oil in sandy sediments was determined. •The effect of input of choline on degradation rates was determined. •16S rRNA clone library analyses were used to examine the microbial phylogeny. •The bacterial community was consisted of clones related to hydrocarbon degraders. •Hydrocarbon degradation in sandy sediments was accelerated by addition of choline. -- Choline, a naturally occurring methylated nitrogen-containing compound, accelerated hydrocarbon degradation in sandy sediments by an extant microbial community

  11. Choline chloride based ionic liquid analogues as tool for the fabrication of agar films with improved mechanical properties

    Science.gov (United States)

    In the present paper, we test the suitability of Choline-Cl/urea (DES-U) and Choline-Cl/glycerol (DES-G) eutectic mixtures at 1:2 molar ratios for the production of agar biodegradable films. A three-step process is proposed: pre-solubilization of polymer in DES followed by compression-molding and s...

  12. Dietary folate and choline status differentially affect lipid metabolism and behavior-mediated neurotransmitters in young rats

    Science.gov (United States)

    The relationship between choline and folate metabolisms is an important issue due to the essential role of these nutrients in brain plasticity and cognitive functions. Present study was designed to investigate whether modification of the dietary folate-choline status in young rats would affect brain...

  13. Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Kakihana, M.; Fukuda, N.; Suno, M.; Nagaoka, A.

    1988-02-01

    The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled (/sup 14/C)glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-(1,2-/sup 14/C)choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis.

  14. Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia

    International Nuclear Information System (INIS)

    Kakihana, M.; Fukuda, N.; Suno, M.; Nagaoka, A.

    1988-01-01

    The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled [ 14 C]glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-[1,2- 14 C]choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis

  15. A Facile, Choline Chloride/Urea Catalyzed Solid Phase Synthesis of Coumarins via Knoevenagel Condensation

    Directory of Open Access Journals (Sweden)

    Hosanagara N. Harishkumar

    2011-01-01

    Full Text Available The influence of choline chloride/urea ionic liquid in solid phase on the Knoevenagel condensation is demonstrated. The active methylene compounds such as meldrum’s acid, diethylmalonate, ethyl cyanoacetate, dimethylmalonate, were efficiently condensed with various salicylaldehydes in presence of choline chloride/urea ionic liquid without using any solvents or additional catalyst. The reaction is remarkably facile because of the air and water stability of the catalyst, and needs no special precautions. The reactions were completed within 1hr with excellent yields (95%. The products formed were sufficiently pure, and can be easily recovered. The use of ionic liquid choline chloride/urea in solid phase offered several significant advantages such as low cost, greater selectivity and easy isolation of products.

  16. Selective retrograde labeling of cholinergic neurons with [3H]choline

    International Nuclear Information System (INIS)

    Bagnoli, P.; Beaudet, A.; Stella, M.; Cuenod, M.

    1981-01-01

    Evidence is presented which is consistent with a specific retrograde labeling of cholinergic neurons following [ 3 H]choline application in their zone of termination. [ 3 H]Choline injection in the rat hippocampus leads to perikaryal retrograde labeling in the ipsilateral medial septal nuclease and nucleus of the diagonal band, thus delineating an established cholinergic pathway, while only diffuse presumably anterograde labeling was observed in the lateral septum, the entorhinal cortex, and the opposite hippocampus. After [ 3 H]choline injection in the pigeon visual Wulst, only the ipsilateral thalamic relay, of all inputs, showed similar perikaryal retrograde labeling, an observation supporting the suggestion that at least some thalamo-Wulst neurons are cholinergic

  17. Catalytic Conversion of Carbohydrates to Furanic Derivatives in the Presence of Choline Chloride

    Directory of Open Access Journals (Sweden)

    François Jérôme

    2017-07-01

    Full Text Available The synthesis of furanic derivatives (5-hydroxymethylfurfural (HMF, furfural… from carbohydrates is of high interest for a wide range of applications. These reactions are carried out in the presence of various solvents, and among them choline chloride can be used. It is a salt that can form a low melting mixture with a carbohydrate (fructose, glucose… or a deep eutectic mixture with carboxylic acid. A review of the studies performed in the conversion of carbohydrates to furanic derivatives in the presence of choline chloride is presented here with the advantages and drawbacks of this solvent. Choline chloride can enhance the selectivity to HMF by stabilizing effect and allows the conversion of highly concentrated feed. However, the extraction of the products from these solvents still needs improvement.

  18. Synthesis and study of thiocarbonate derivatives of choline as potential inhibitors of acetylcholinesterase.

    Science.gov (United States)

    Boyle, N A; Talesa, V; Giovannini, E; Rosi, G; Norton, S J

    1997-09-12

    Fourteen alkyl and aryl thiocarbonate derivatives of choline were synthesized and studied as potential inhibitors of acetylcholinesterase (AChE). Twelve of the compounds inhibited AChEs derived from calf forebrain, human red blood cells, and octopus brain ranging from low to moderately high inhibition potency. The concentration of each inhibitory compound giving 50% inhibition of enzyme activity (IC50 values, which ranged from 1 x 10(-2) to 8 x 10(-7) M) was determined and is reported; inhibitor constants (Ki values) for the most inhibitory compounds, (1-pentylthiocarbonyl)choline chloride and (1-heptylthiocarbonyl)choline chloride, were calculated from kinetic data and are also reported. The inhibitors are competitive with substrate, and they are not hydrolyzed by the AChE activities. Certain of these new compounds may provide direction for the development of new drugs that have anticholinesterase activity and may be used for the treatment of Alzheimer's disease.

  19. Review on Carbon Dioxide Absorption by Choline Chloride/Urea Deep Eutectic Solvents

    Directory of Open Access Journals (Sweden)

    Rima J. Isaifan

    2018-01-01

    Full Text Available In the recent past few years, deep eutectic solvents (DESs were developed sharing similar characteristics to ionic liquids but with more advantageous features related to preparation cost, environmental impact, and efficiency for gas separation processes. Amongst many combinations of DES solvents that have been prepared, reline (choline chloride as the hydrogen bond acceptor mixed with urea as the hydrogen bond donor was the first DES synthesized and is still the one with the lowest melting point. Choline chloride/urea DES has proven to be a promising solvent as an efficient medium for carbon dioxide capture when compared with amine alone or ionic liquids under the same conditions. This review sheds light on the preparation method, physical and chemical characteristics, and the CO2 absorption capacity of choline chloride/urea DES under different temperatures and pressures reported up to date.

  20. Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis.

    Science.gov (United States)

    Ganz, Ariel B; Shields, Kelsey; Fomin, Vlad G; Lopez, Yusnier S; Mohan, Sanjay; Lovesky, Jessica; Chuang, Jasmine C; Ganti, Anita; Carrier, Bradley; Yan, Jian; Taeswuan, Siraphat; Cohen, Vanessa V; Swersky, Camille C; Stover, Julie A; Vitiello, Gerardo A; Malysheva, Olga V; Mudrak, Erika; Caudill, Marie A

    2016-10-01

    Although single nucleotide polymorphisms (SNPs) in folate-mediated pathways predict susceptibility to choline deficiency during severe choline deprivation, it is unknown if effects persist at recommended intakes. Thus, we used stable isotope liquid chromatography-mass spectrometry (LC-MS) methodology to examine the impact of candidate SNPs on choline metabolism in a long-term, randomized, controlled feeding trial among pregnant, lactating, and nonpregnant (NP) women consuming 480 or 930 mg/d choline (22% as choline-d 9 , with d 9 indicating a deuterated trimethyl amine group) and meeting folate-intake recommendations. Variants impairing folate metabolism, methylenetetrahydrofolate reductase (MTHFR) rs1801133, methionine synthase (MTR) rs1805087 [wild-type (WT)], MTR reductase (MTRR) rs1801394, and methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase (MTHFD1) rs2236225, influenced choline dynamics, frequently through interactions with reproductive state and choline intake, with fewer genotypic alterations observed among pregnant women. Women with these variants partitioned more dietary choline toward phosphatidylcholine (PC) biosynthesis via the cytidine diphosphate (CDP)-choline pathway at the expense of betaine synthesis even when use of betaine as a methyl donor was increased. Choline intakes of 930 mg/d restored partitioning of dietary choline between betaine and CDP-PC among NP (MTHFR rs1801133 and MTR rs1805087 WT) and lactating (MTHFD1 rs2236225) women with risk genotypes. Overall, our findings indicate that loss-of-function variants in folate-metabolizing enzymes strain cellular PC production, possibly via impaired folate-dependent phosphatidylethanolamine-N-methyltransferase (PEMT)-PC synthesis, and suggest that women with these risk genotypes may benefit from choline intakes exceeding current recommendations.-Ganz, A. B., Shields, K., Fomin, V. G., Lopez, Y. S., Mohan, S., Lovesky, J., Chuang, J

  1. Choline and its metabolites are differently associated with cardiometabolic risk factors, cardiovascular history and MRI documented cerebrovascular disease in older adults

    Science.gov (United States)

    Background: There is a potential role of choline in cardiovascular and cerebrovascular disease through its involvement in lipid and one-carbon metabolism. Objective: We evaluated the associations of plasma choline and choline-related compounds with cardiometabolic risk factors, history of cardiovas...

  2. Dietary choline levels modify the effects of prenatal alcohol exposure in rats.

    Science.gov (United States)

    Idrus, Nirelia M; Breit, Kristen R; Thomas, Jennifer D

    Prenatal alcohol exposure can cause a range of physical and behavioral alterations; however, the outcome among children exposed to alcohol during pregnancy varies widely. Some of this variation may be due to nutritional factors. Indeed, higher rates of fetal alcohol spectrum disorders (FASD) are observed in countries where malnutrition is prevalent. Epidemiological studies have shown that many pregnant women throughout the world may not be consuming adequate levels of choline, an essential nutrient critical for brain development, and a methyl donor. In this study, we examined the influence of dietary choline deficiency on the severity of fetal alcohol effects. Pregnant Sprague-Dawley rats were randomly assigned to receive diets containing 40, 70, or 100% recommended choline levels. A group from each diet condition was exposed to ethanol (6.0g/kg/day) from gestational day 5 to 20 via intubation. Pair-fed and ad lib lab chow control groups were also included. Physical and behavioral development was measured in the offspring. Prenatal alcohol exposure delayed motor development, and 40% choline altered performance on the cliff avoidance task, independent of one another. However, the combination of low choline and prenatal alcohol produced the most severe impairments in development. Subjects exposed to ethanol and fed the 40% choline diet exhibited delayed eye openings, significantly fewer successes in hindlimb coordination, and were significantly overactive compared to all other groups. These data suggest that suboptimal intake of a single nutrient can exacerbate some of ethanol's teratogenic effects, a finding with important implications for the prevention of FASD. Copyright © 2016. Published by Elsevier Inc.

  3. An electrochemiluminescence-based fibre optic biosensor for choline flow injection analysis.

    Science.gov (United States)

    Tsafack, V C; Marquette, C A; Leca, B; Blum, L J

    2000-01-01

    A fibre optic biosensor based on luminol electrochemiluminescence (ECL) integrated in a flow injection analysis (FIA) system was developed for the detection of choline. The electrochemiluminescence of luminol was generated by a glassy carbon electrode polarised at +425 mV vs. a platinum pseudo-reference electrode. Choline oxidase (Chx) was immobilised either covalently on polyamide (ABC type) or on UltraBind preactivated membranes, or by physical entrapment in a photo-cross-linkable poly(vinyl alcohol) polymer (PVA-SbQ) alone or after absorption on a weak anion exchanger, DEAE (diethylaminoethyl) Sepharose. The optimisation of the reaction conditions and physicochemical parameters influencing the FIA biosensor response demonstrated that the choline biosensor exhibited the best performances in a 30 mM veronal buffer containing 30 mM KCl and 1.5 mM MgCl2, at pH 9. The use of a 0.5 ml min-1 flow rate enabled the measurement of choline by the membrane-based ECL biosensors in 8 or 5 min, with ABC or UltraBind membranes, respectively, whereas the measurement required only 3 min with the DEAE-PVA system. For comparison, the detection of choline was performed with Chx immobilised using the four different supports. The best performances were obtained with the DEAE-PVA-Chx sensing layer, which allowed a detection limit of 10 pmol, whereas with the ABC, the UltraBind and the PVA systems, the detection limits were 300 pmol, 75 pmol and 220 pmol, respectively. The DEAE-based system also exhibited a good operational stability since 160 repeated measurements of 3 nmol of choline could be performed with an RSD of 4.5% whereas the stability under the best conditions was 45 assays with the other supports.

  4. Role of carbon-11 choline PET/CT in the management of uterine carcinoma. Initial experience

    International Nuclear Information System (INIS)

    Sofue, Keitaro; Sawada, Morio; Arai, Yasuaki; Tateishi, Ukihide; Inoue, Tomio; Maeda, Tetsuo; Sugimura, Kazuro; Terauchi, Takashi; Kano, Daisuke

    2009-01-01

    The present study was conducted to clarify the role of carbon-11 choline ( 11 C-choline) positron emission tomography (PET)/computed tomography (CT) in the management of uterine carcinoma. Twenty-two patients who underwent 11 C-choline PET/CT and pelvic MRI were evaluated retrospectively. The images were reviewed by a board-certified radiologist and a nuclear medicine specialist who were unaware of any clinical information, and a consensus was reached. Diagnostic accuracy of PET/CT was evaluated for staging. The reference standard consisted of histological examination (n=17) and follow-up conventional CT (n=5). In five patients with cervical carcinoma, 11 C-choline PET/CT was performed before and after treatment that consisted of cisplatin infusion and subsequent radiotherapy. Standardized uptake value (SUV) was compared with unidimensional and volumetric measurements that were made on magnetic resonance images (MRI) before and after treatment. Based on PET/CT interpretations, the reviewers correctly classified tumor (T) stage in 8 patients (47%), nodes (N) stage in 21 patients (96%), metastasis (M) stage in 20 patients (91%), and tumor, nodes and metastasis (TNM) stage in 15 patients (88%). Tumor size, volume, and SUV decreased after treatment in five patients with cervical carcinoma. Using the Pearson correlation test, a significant correlation was found between the reduction rate of SUV and reduction rate of tumor volume. 11 C-choline PET/CT is an accurate means for the management of patients with uterine carcinoma. The combination of 11 C-choline PET/CT and MRI increases the accuracy of staging in patients with uterine carcinoma. (author)

  5. Prostate cancer: concordance between "1"8F-choline PET and CT in biochemical relapse

    International Nuclear Information System (INIS)

    Herández Pinzón, J.; Ferrarotti, C.; Ferrari, L.; Larrañaga, N.; Gallo, J.C.; Mena, D.; Bastianello, M.

    2016-01-01

    Objective: To establish the concordance between 18-fluor choline positron emission tomography (PET) and computed tomography (CT) for re-staging patients with biochemical relapse of prostate cancer according to the TNM system. Materials and methods: The medical records of the Molecular Imaging Section were retrospectively reviewed. The TNM classification was established by us for each method, and the Kappa concordance statistic was used to classify the results according to the Landis and Koch proposal. Results: The PET-choline reported 19 (59.4%) patients N0 and 13 (40.6%) N1, while CT reported 28 (87.5%) N0 and 4 (12.5%) N1. In metastasis classification PET-choline established M0 in 17 (53.1%) patients, M1a in 1 (3.1%), M1b in 5 (15.6%), M1c in 1 (3.1%), M1a + M1b in 7 (21.9%), and M1b + M1c in 1 (3.1%). On the other hand, CT was M0 in 23 (71.9%) patients, M1a in 2 (6.25%), M1a + M1b in 2 (6.25%), and M1b + M1c in 5 (15.6%). The correlation between PET-choline and CT in the TNM lymph node and metastasis classifications was 71.88%, with a Kappa of 0.3455 (standard error 0.1336; P=.0049) and 62.5% with Kappa 0.3725 (standard error 0.0847; P=.0001), respectively. Discussion: Several studies have shown a high diagnostic accuracy of PET-choline detecting the spread of the disease compared to conventional methods. Conclusion: There is poor concordance for metastatic and lymph node classifications according to the TNM system between choline-PET and CT. (authors) [es

  6. Effect of quinolinic acid in the nucleus basalis magnocellularis on cortical high-affinity choline uptake

    Energy Technology Data Exchange (ETDEWEB)

    Metcalf, R.H.; Boegman, R.J.; Quirion, R.; Riopelle, R.J.; Ludwin, S.K.

    1987-08-01

    A transient 45% increase in cortical high-affinity choline uptake (HACU) was observed after an injection of quinolinic acid (QUIN) into the nucleus basalis magnocellularis (nbM) of the rat. This was followed by a steady decline in choline uptake, which resulted in a 46% decrease by day 7. Specific (/sup 3/H)hemicholinium-3 binding to coronal brain sections showed a similar pattern following injections of QUIN into the nbM. The increase in cortical HACU elicited by QUIN appeared to be dose dependent.

  7. A mechanism for suppression of the CDP-choline pathway during apoptosis

    OpenAIRE

    Morton, Craig C.; Aitchison, Adam J.; Gehrig, Karsten; Ridgway, Neale D.

    2013-01-01

    Inhibition of the CDP-choline pathway during apoptosis restricts the availability of phosphatidylcholine (PtdCho) for assembly of membranes and synthesis of signaling factors. The N-terminal nuclear localization signal (NLS) in CTP:phosphocholine cytidylyltransferase (CCT)α is removed during apoptosis but the caspase(s) involved and the contribution to suppression of the CDP-choline pathway is unresolved. In this study we utilized siRNA silencing of caspases in HEK293 cells and caspase 3-defi...

  8. Characterization and detection of a widely distributed gene cluster that predicts anaerobic choline utilization by human gut bacteria.

    Science.gov (United States)

    Martínez-del Campo, Ana; Bodea, Smaranda; Hamer, Hilary A; Marks, Jonathan A; Haiser, Henry J; Turnbaugh, Peter J; Balskus, Emily P

    2015-04-14

    Elucidation of the molecular mechanisms underlying the human gut microbiota's effects on health and disease has been complicated by difficulties in linking metabolic functions associated with the gut community as a whole to individual microorganisms and activities. Anaerobic microbial choline metabolism, a disease-associated metabolic pathway, exemplifies this challenge, as the specific human gut microorganisms responsible for this transformation have not yet been clearly identified. In this study, we established the link between a bacterial gene cluster, the choline utilization (cut) cluster, and anaerobic choline metabolism in human gut isolates by combining transcriptional, biochemical, bioinformatic, and cultivation-based approaches. Quantitative reverse transcription-PCR analysis and in vitro biochemical characterization of two cut gene products linked the entire cluster to growth on choline and supported a model for this pathway. Analyses of sequenced bacterial genomes revealed that the cut cluster is present in many human gut bacteria, is predictive of choline utilization in sequenced isolates, and is widely but discontinuously distributed across multiple bacterial phyla. Given that bacterial phylogeny is a poor marker for choline utilization, we were prompted to develop a degenerate PCR-based method for detecting the key functional gene choline TMA-lyase (cutC) in genomic and metagenomic DNA. Using this tool, we found that new choline-metabolizing gut isolates universally possessed cutC. We also demonstrated that this gene is widespread in stool metagenomic data sets. Overall, this work represents a crucial step toward understanding anaerobic choline metabolism in the human gut microbiota and underscores the importance of examining this microbial community from a function-oriented perspective. Anaerobic choline utilization is a bacterial metabolic activity that occurs in the human gut and is linked to multiple diseases. While bacterial genes responsible for

  9. Effect of CDP-choline on the biosynthesis of phospholipids in brain regions during hypoxic treatment

    International Nuclear Information System (INIS)

    Alberghina, M.; Viola, M.; Serra, I.; Mistretta, A.; Giuffrida, A.M.

    1981-01-01

    Acute administration of CDP-choline (i.p. 100 mg/Kg b.w.), 10 min before the intraventricular injection of labeled precursors, [2-3H] glycerol and [1-14C]-palmitate, was able to correct the impairment caused by hypoxic treatment of lipid metabolism in some brain regions, ie, cerebral hemispheres, cerebellum, and brainstem. After CDP-choline treatment, an increase of the specific radioactivity of total lipids and of phospholipids was observed in mitochondria purified from the three above-mentioned brain regions of the hypoxic animals, while no effect on the other subcellular fractions was found. CDP-Choline had a stimulating effect particularly on the incorporation of both precursors into mitochondrial PC, PE, and polyglycerophosphatides isolated form the three brain regions examined. The results obtained show that the action of CDP-choline in restoring lipid metabolism was more pronounced in brain mitochondria, which, among subcellular fractions, were the most affected by the hypoxic treatment

  10. Comparable stability of Hoogsteen and Watson-Crick base pairs in ionic liquid choline dihydrogen phosphate.

    Science.gov (United States)

    Tateishi-Karimata, Hisae; Nakano, Miki; Sugimoto, Naoki

    2014-01-08

    The instability of Hoogsteen base pairs relative to Watson-Crick base pairs has limited biological applications of triplex-forming oligonucleotides. Hydrated ionic liquids (ILs) provide favourable environments for a wide range of chemical reactions and are known to impact the stabilities of Watson-Crick base pairs. We found that DNA triplex formation was significantly stabilized in hydrated choline dihydrogen phosphate as compared with an aqueous buffer at neutral pH. Interestingly, the stability of Hoogsteen base pairs was found to be comparable with that of Watson-Crick base pairs in the hydrated IL. Molecular dynamics simulations of a DNA triplex in the presence of choline ions revealed that the DNA triplex was stabilized because of the binding of choline ion around the third strand in the grooves. Our finding will facilitate the development of new DNA materials. Our data also indicate that triplex formation may be stabilized inside cells where choline ions and their derivatives are abundant in vivo.

  11. Comparable Stability of Hoogsteen and Watson–Crick Base Pairs in Ionic Liquid Choline Dihydrogen Phosphate

    Science.gov (United States)

    Tateishi-Karimata, Hisae; Nakano, Miki; Sugimoto, Naoki

    2014-01-01

    The instability of Hoogsteen base pairs relative to Watson–Crick base pairs has limited biological applications of triplex-forming oligonucleotides. Hydrated ionic liquids (ILs) provide favourable environments for a wide range of chemical reactions and are known to impact the stabilities of Watson–Crick base pairs. We found that DNA triplex formation was significantly stabilized in hydrated choline dihydrogen phosphate as compared with an aqueous buffer at neutral pH. Interestingly, the stability of Hoogsteen base pairs was found to be comparable with that of Watson–Crick base pairs in the hydrated IL. Molecular dynamics simulations of a DNA triplex in the presence of choline ions revealed that the DNA triplex was stabilized because of the binding of choline ion around the third strand in the grooves. Our finding will facilitate the development of new DNA materials. Our data also indicate that triplex formation may be stabilized inside cells where choline ions and their derivatives are abundant in vivo. PMID:24399194

  12. Maternal Choline Supplementation: A Potential Prenatal Treatment for Down Syndrome and Alzheimer's Disease.

    Science.gov (United States)

    Strupp, Barbara J; Powers, Brian E; Velazquez, Ramon; Ash, Jessica A; Kelley, Christy M; Alldred, Melissa J; Strawderman, Myla; Caudill, Marie A; Mufson, Elliott J; Ginsberg, Stephen D

    2016-01-01

    Although Down syndrome (DS) can be diagnosed prenatally, currently there are no effective treatments to lessen the intellectual disability (ID) which is a hallmark of this disorder. Furthermore, starting as early as the third decade of life, DS individuals exhibit the neuropathological hallmarks of Alzheimer's disease (AD) with subsequent dementia, adding substantial emotional and financial burden to their families and society at large. A potential therapeutic strategy emerging from the study of trisomic mouse models of DS is to supplement the maternal diet with additional choline during pregnancy and lactation. Studies demonstrate that maternal choline supplementation (MCS) markedly improves spatial cognition and attentional function, as well as normalizes adult hippocampal neurogenesis and offers protection to basal forebrain cholinergic neurons (BFCNs) in the Ts65Dn mouse model of DS. These effects on neurogenesis and BFCNs correlate significantly with spatial cognition, suggesting functional relationships. In this review, we highlight some of these provocative findings, which suggest that supplementing the maternal diet with additional choline may serve as an effective and safe prenatal strategy for improving cognitive, affective, and neural functioning in DS. In light of growing evidence that all pregnancies would benefit from increased maternal choline intake, this type of recommendation could be given to all pregnant women, thereby providing a very early intervention for individuals with DS, and include babies born to mothers unaware that they are carrying a fetus with DS.

  13. Studies on the riboflavin, niacin, pantothenic acid and choline requirements of young bobwhite quail

    Science.gov (United States)

    Serafin, J.A.

    1974-01-01

    Four experiments were conducted to examine the riboflavin, niacin, pantothenic acid and choline requirements of young Bobwhite quail. Quail fed purified diets deficient in either riboflavin, niacin, pantothenic acid or choline grew poorly and high mortality occurred by 5 weeks of age. Under the conditions of these experiments, it was found that: (1) young quail require approximately 3.8 mg. riboflavin/kg. diet for satisfactory growth and survival; (2) no more than 31 mg. niacin/kg. diet are required for normal growth and survival of young quail; (3) the requirement for pantothenic acid is higher than has previously been reported, quail in these studies requiring 12.6 mg. pantothenic acid/kg. feed for growth and survival; and (4) the requirement for choline for reducing mortality is approximately 1000 mg./kg., while the amount necessary for normal growth of young quail is no greater than 1500 mg./kg. when the diet contains ample amounts of methionine. Quail fed a niacin-deficient diet developed stiff, shortened feathers and an erythema about the head; those receiving a riboflavin-deficient ration developed enlarged hocks and bowed legs, as did quail fed diets low or devoid of choline. Aside from slow growth, poor feathering was the only other indication that a deficient diet was being fed when quail were placed on a basal ration without pantothenic acid for five weeks.

  14. Studies on the riboflavin, pantothenic acid, nicotinic acid and choline requirements of young Embden geese

    Science.gov (United States)

    Serafin, J.A.

    1981-01-01

    Four experiments were conducted to examine the riboflavin, pantothenic acid, nicotinic acid, and choline requirements of young Embden geese fed purified diets. Goslings fed diets deficient in either riboflavin, pantothenic acid, nicotinic acid, or choline grew poorly. Feeding a pantothenic acid-deficient diet resulted in 100% mortality. Goslings fed diets containing 530 mg/kg of choline or less developed perosis. Under the conditions of these experiments it was found that: 1) goslings require no more than 3.84 mg/kg of riboflavin and 31.2 mg/kg of nicotinic acid in the diet for rapid growth and normal development, 2) the pantothenic acid requirement of goslings is no more than 12.6 mg/kg of diet, and 3) a dietary choline level of 1530 mg/kg is adequate for both the prevention of perosis and rapid growth of goslings. The levels of vitamins found to support normal growth and development of goslings appear to be similar to requirements of other species that have been examined.

  15. Effect of herbal choline and rumen-protected methionine on lamb ...

    African Journals Online (AJOL)

    Elizabeth A Mendoza B MD

    2018-01-30

    Jan 30, 2018 ... oral doses of rumen-protected methionine (RPM) (0 and 1.5 g/day) and ... and stimulating glucose and cholesterol synthesis. .... The in vitro gas production indicates that half of herbal choline is fermented at 18 hours (Table 2),.

  16. Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women.

    NARCIS (Netherlands)

    Dalmeijer, G.W.; Olthof, M.R.; Verhoef, P.; Bots, M.L.; van der Schouw, Y.T.

    2008-01-01

    Objective: To investigate the association between dietary intakes of folate, betaine and choline and the risk of cardiovascular disease (CVD). Design: Prospective cohort study. Subjects: A total of 16165 women aged 49-70 years without prior CVD. Subjects were breast cancer screening participants in

  17. Inhibition of high affinity choline uptake by N-allyl-3-quinuclidinol

    International Nuclear Information System (INIS)

    Asermely, K.E.; O'Neill, J.J.

    1986-01-01

    The peripheral actions of N-allyl-3-quinuclidinol (N-Al-3-OHQ) on high affinity choline uptake (HAChU) on rat phrenic nerve diaphragm are described. Endplate regions (EPA) identified by the Koelle histochemical techniques for acetylcholinesterase, were dissected from adult rat hemidiaphragms and placed in cold Krebs solution (pH-7.35). All measurements of HAChU were at 37 0 C in buffers containing tritium choline (5 μM 0.124 μC/mmole) at intervals of 1, 2, 4, 8, 15 and 30 min. Tissues were washed 3x, digested in 1N NaOH and counted for tritium in Chaikoff's solution. All data are expressed as pmole Ch/g wet weight. Comparison between EPA and non-EPA tissue demonstrate HAChU and slow choline diffusion, respectively. Steady state is observed in 15 min. N-Al-3-OHQ produces 15% inhibition at 5 x 10 -5 M compared with 50% inhibition on brain synaptosomes. At 5 x 10 -4 M N-Al-3-OHQ, 30% inhibition is observed. Attempts to deplete ACh by pre-stimulation with high K + -ion (25 mM) were unsuccessful; tissue 3 H-choline uptake appeared to oscillate over a 30 min period

  18. Inhibition of high affinity choline uptake by N-allyl-3-quinuclidinol

    Energy Technology Data Exchange (ETDEWEB)

    Asermely, K.E.; O' Neill, J.J.

    1986-03-01

    The peripheral actions of N-allyl-3-quinuclidinol (N-Al-3-OHQ) on high affinity choline uptake (HAChU) on rat phrenic nerve diaphragm are described. Endplate regions (EPA) identified by the Koelle histochemical techniques for acetylcholinesterase, were dissected from adult rat hemidiaphragms and placed in cold Krebs solution (pH-7.35). All measurements of HAChU were at 37/sup 0/C in buffers containing tritium choline (5 ..mu..M 0.124 ..mu..C/mmole) at intervals of 1, 2, 4, 8, 15 and 30 min. Tissues were washed 3x, digested in 1N NaOH and counted for tritium in Chaikoff's solution. All data are expressed as pmole Ch/g wet weight. Comparison between EPA and non-EPA tissue demonstrate HAChU and slow choline diffusion, respectively. Steady state is observed in 15 min. N-Al-3-OHQ produces 15% inhibition at 5 x 10/sup -5/ M compared with 50% inhibition on brain synaptosomes. At 5 x 10/sup -4/ M N-Al-3-OHQ, 30% inhibition is observed. Attempts to deplete ACh by pre-stimulation with high K/sup +/-ion (25 mM) were unsuccessful; tissue /sup 3/H-choline uptake appeared to oscillate over a 30 min period.

  19. Choline chloride-based deep eutectic solvents as additives for optimizing chromatographic behavior of caffeic acid

    International Nuclear Information System (INIS)

    Li, Guizhen; Zhu, Tao; Lei, Yingjie

    2015-01-01

    A series of deep eutectic solvents (DESs) were prepared using glycerol and choline chloride (ChCl), and Fourier transform infrared spectrometer (FT-IR) was used to analyze the spectra of glycerol, choline chloride and DESs based on glycerol and choline chloride. Then DESs were used as the additives of mobile phase to optimize chromatographic behavior of caffeic acid in high performance liquid chromatography (HPLC). A 17-run Box-Behnken design (BBD) was employed to evaluate effect of DESs as additives by analyzing the maximum theoretical plate number. Three factors, reaction temperature (60 .deg. C, 80 .deg. C, 100 .deg. C), molar ratio of glycerol and choline chloride (2 : 1, 3 : 1, 4 : 1, n/n), and volume percent of additives (0.05%, 0.10%, 0.15%, v/v), were investigated in BBD. The optimum experiment condition was that of reaction temperature (80 .deg. C), molar ratio of glycerol and ChCl (3 : 1, n/n), and volume percent of additive (0.10%, v/v). The mean chromatographic theoretical plate number of the caffeic acid this condition was 1567.5, and DESs as additives shorten the retention time and modify the chromatogram shape, proving DESs as additives for effective theoretical plate number and column efficiency in HPLC.

  20. Choline chloride-based deep eutectic solvents as additives for optimizing chromatographic behavior of caffeic acid

    Energy Technology Data Exchange (ETDEWEB)

    Li, Guizhen; Zhu, Tao; Lei, Yingjie [Tianjin University of Technology, Tianjin (China)

    2015-10-15

    A series of deep eutectic solvents (DESs) were prepared using glycerol and choline chloride (ChCl), and Fourier transform infrared spectrometer (FT-IR) was used to analyze the spectra of glycerol, choline chloride and DESs based on glycerol and choline chloride. Then DESs were used as the additives of mobile phase to optimize chromatographic behavior of caffeic acid in high performance liquid chromatography (HPLC). A 17-run Box-Behnken design (BBD) was employed to evaluate effect of DESs as additives by analyzing the maximum theoretical plate number. Three factors, reaction temperature (60 .deg. C, 80 .deg. C, 100 .deg. C), molar ratio of glycerol and choline chloride (2 : 1, 3 : 1, 4 : 1, n/n), and volume percent of additives (0.05%, 0.10%, 0.15%, v/v), were investigated in BBD. The optimum experiment condition was that of reaction temperature (80 .deg. C), molar ratio of glycerol and ChCl (3 : 1, n/n), and volume percent of additive (0.10%, v/v). The mean chromatographic theoretical plate number of the caffeic acid this condition was 1567.5, and DESs as additives shorten the retention time and modify the chromatogram shape, proving DESs as additives for effective theoretical plate number and column efficiency in HPLC.

  1. 75 FR 760 - Choline chloride; Exemption from the Requirement of a Tolerance

    Science.gov (United States)

    2010-01-06

    ... affected. The North American Industrial Classification System (NAICS) codes have been provided to assist... body functions including the maintenance of osmotic pressure, acid-base balance, muscular activity, and... nervous system and memory. Choline is necessary to promote proper development in the fetus and infant and...

  2. Effect of addition of Proline, ionic liquid [Choline][Pro] on CO2 separation properties of poly(amidoamine) dendrimer / poly(ethylene glycol) hybrid membranes

    Science.gov (United States)

    Duan, S. H.; Kai, T.; Chowdhury, F. A.; Taniguchi, I.; Kazama, S.

    2018-01-01

    Poly(amidoamine) (PAMAM) dendrimers were incorporated into cross-linked poly(ethylene glycol) (PEGDMA) matrix to improve carbon dioxide (CO2) separation performance at elevated pressures. In our previous studies, PAMAM/PEGDMA hybrid membranes showed high CO2 separation properties from CO2/H2 mixed gases. In this study, proline, choline and ionic liquid [Choline][Pro] compounds were selected as rate promoters that were used to prepare PAMAM/PEGDMA hybrid membranes. The effect of addition of proline, choline, IL [Choline][Pro] on separation performance of PAMAM/PEGDMA) hybrid membranes for CO2/H2 separation was investigated. Amino acid proline, choline, and IL [Choline][Pro] were used to promote CO2 and amine reaction. With the addition of [Choline][Pro] into PAMAM/PEG membrane, CO2 permeance of PAMAM/PEG hybrid membranes are increased up to 46% without any change of selectivity of membrane for CO2.

  3. Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice.

    Science.gov (United States)

    Zhang, Jianhai; Zhang, Yufang; Liang, Chen; Wang, Nasui; Zheng, Heping; Wang, Jundong

    2016-11-01

    Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150mg/L NaF in drinking water, 5.75g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Galvanostatic bottom-up filling of TSV-like trenches: Choline-based leveler containing two quaternary ammoniums

    International Nuclear Information System (INIS)

    Kim, Myung Jun; Seo, Youngran; Kim, Hoe Chul; Lee, Yoonjae; Choe, Seunghoe; Kim, Young Gyu; Cho, Sung Ki; Kim, Jae Jeong

    2015-01-01

    Highlights: • The choline-based leveler having two quaternary ammoniums was synthesized. • The adsorption of this leveler with suppressor and accelerator was examined. • Galvanostatic Cu bottom-up filling was achieved with three-additive system. • The mechanism of gap-filling was elucidated based on the additive adsorption. - Abstract: Through Silicon Via (TSV) technology is essential to accomplish 3-dimensional packaging of electronics. Hence, more reliable and faster TSV filling by Cu electrodeposition is required. Our approach to improve Cu gap-filling in TSV is based on the development of new organic additives for feature filling. Here, we introduce our achievements from the synthesis of choline-based leveler to the feature filling using a synthesized leveler. The choline-based leveler, which includes two quaternary ammoniums at both ends of the molecule, is synthesized from glutaric acid. The characteristics of the choline-based additive are examined by the electrochemical analyses, and it is confirmed that the choline-based leveler shows a convection dependent adsorption behavior, which is essential for leveling. The interactions between the polymeric suppressor, accelerator, and the choline-based leveler are also investigated by changing the convection condition. Using the combination of suppressor, accelerator, and the choline-based leveler, the extreme bottom-up filling of Cu at trenches with dimensions similar to TSV are fulfilled. The mechanism of Cu gap-filling is demonstrated based on the results of electrochemical analyses and feature filling

  5. Effect of dimethylaminoethanol, an inhibitor of betaine production, on the disposition of choline in the rat kidney

    International Nuclear Information System (INIS)

    Lohr, J.; Acara, M.

    1990-01-01

    The choline metabolite betaine has been shown to be an important organic osmoregulatory solute in the kidney. The isolated perfused rat kidney and kidney slice incubations were used to investigate the effect of 2-dimethylaminoethanol (DMAE), a choline oxidase inhibitor, on the renal excretion and metabolism of choline. In the isolated perfused kidney, [ 14 C]choline, at an initial perfusate concentration of 300 microM, was effectively removed from the perfusate over 25 min, with nearly all the 14 C in the perfusate accounted for by betaine during the remainder of the 90-min perfusion. DMAE at concentrations of 3.0 or 5.0 mM significantly decreased the rate of removal of [ 14 C]choline from the perfusate and the rate of addition of [ 14 C]betaine to the perfusate, yet [14C]betaine remained the only metabolite of choline in perfusate and urine. In kidney tissue slice experiments, conversion of [ 14 C]choline to [ 14 C]betaine was found in cortical, outer medullary and inner medullary regions of rat kidney. DMAE at 5.0 mM significantly inhibited [ 14 C]betaine production in each of the three regions studied. These data show that DMAE is an effective inhibitor of betaine production by the kidney and, as such, may be an important agent for the study of osmoregulation by the kidney

  6. Measurement of concentrations of whole blood levels of choline, betaine, and dimethylglycine and their relations to plasma levels.

    Science.gov (United States)

    Awwad, Hussain Mohamad; Kirsch, Susanne H; Geisel, Juergen; Obeid, Rima

    2014-04-15

    We aimed at developing a method for the measurement of choline and its metabolites in whole blood (WB). After an extraction step, quantification of choline, betaine, and dimethylglycine (DMG) was performed using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Plasma and WB metabolites were evaluated in a group of 61 elderly people. The calibration curves were linear (r(2)>0.997) for all compounds. The inter- and intra-assay coefficients of variation for all analytes were 90% and the relative matrix effect were ≤4.0%. The median concentrations of choline, betaine, and DMG were 11.3, 27.8, and 5.9μmol/L in plasma and 66.6, 165, and 13.7μmol/L in WB, respectively. There were positive correlations between WB and plasma markers; for choline (r=0.42), betaine (r=0.61), and DMG (r=0.56) (all p≤0.001). The concentrations of betaine in WB and plasma were significantly higher in men than in women. The concentrations of WB choline and DMG did not differ significantly according to sex. In conclusion, we have established a reliable method for measuring choline metabolites in WB. The concentrations of WB choline, betaine, and DMG seem to reflect intracellular concentrations of these metabolites. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Prenatal choline supplementation attenuates MK-801-induced deficits in memory, motor function, and hippocampal plasticity in adult male rats.

    Science.gov (United States)

    Nickerson, Chelsea A; Brown, Alexandra L; Yu, Waylin; Chun, Yoona; Glenn, Melissa J

    2017-10-11

    Choline is essential to the development and function of the central nervous system and supplemental choline during development is neuroprotective against a variety of insults, including neurotoxins like dizocilpine (MK-801). MK-801 is an NMDA receptor antagonist that is frequently used in rodent models of psychological disorders, particularly schizophrenia. At low doses, it causes cognitive impairments, and at higher doses it induces motor deficits, anhedonia, and neuronal degeneration. The primary goals of the present study were to investigate whether prenatal choline supplementation protects against the cognitive impairments, motor deficits, and neuropathologies that are precipitated by MK-801 administration in adulthood. Adult male Sprague-Dawley rats were fed a standard or supplemented choline diet prenatally. Using the novelty preference test of object recognition, we found that only prenatal standard-fed rats displayed memory consolidation deficits induced by low-dose MK-801 administered immediately following study of sample objects; all other groups, including prenatal choline supplemented rats given MK-801, showed intact memory. Following high-dose MK-801, prenatal choline supplementation significantly alleviated rats' motor response to MK-801, particularly ataxia. Using doublecortin and Ki67 to mark neurogenesis and cell division, respectively, in the hippocampus, we found that prenatal choline supplementation, in the face of MK-801 toxicity, protected against reduced hippocampal plasticity. Taken together, the current findings suggest that prenatal choline supplementation protects against a variety of behavioral and neural pathologies induced by the neurotoxin, MK-801. This research contributes to the growing body of evidence supporting the robust neuroprotective capacity of choline. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Editor's Highlight: Perfluorooctane Sulfonate-Choline Ion Pair Formation: A Potential Mechanism Modulating Hepatic Steatosis and Oxidative Stress in Mice.

    Science.gov (United States)

    Zhang, Limin; Krishnan, Prasad; Ehresman, David J; Smith, Philip B; Dutta, Mainak; Bagley, Bradford D; Chang, Shu-Ching; Butenhoff, John L; Patterson, Andrew D; Peters, Jeffrey M

    2016-09-01

    The mechanisms underlying perfluorooctane sulfonate (PFOS)-induced steatosis remain unclear. The hypothesis that PFOS causes steatosis and other hepatic effects by forming an ion pair with choline was examined. C57BL/6 mice were fed either a control diet or a marginal methionine/choline-deficient (mMCD) diet, with and without 0.003, 0.006, or 0.012% potassium PFOS. Dietary PFOS caused a dose-dependent decrease in body weight, and increases in the relative liver weight, hepatic triglyceride concentration and serum markers of liver toxicity and oxidative stress. Some of these effects were exacerbated in mice fed the mMCD diet supplemented with 0.012% PFOS compared with those fed the control diet supplemented with 0.012% PFOS. Surprisingly, serum PFOS concentrations were higher while liver PFOS concentrations were lower in mMCD-fed mice compared with corresponding control-fed mice. To determine if supplemental dietary choline could prevent PFOS-induced hepatic effects, C57BL/6 mice were fed a control diet, or a choline supplemental diet (1.2%) with or without 0.003% PFOS. Lipidomic analysis demonstrated that PFOS caused alterations in hepatic lipid metabolism in the PFOS-fed mice compared with controls, and supplemental dietary choline prevented these PFOS-induced changes. Interestingly, dietary choline supplementation also prevented PFOS-induced oxidative damage. These studies are the first to suggest that PFOS may cause hepatic steatosis and oxidative stress by effectively reducing the choline required for hepatic VLDL production and export by forming an ion pair with choline, and suggest that choline supplementation may prevent and/or treat PFOS-induced hepatic steatosis and oxidative stress. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Metabolism of choline in brain of the aged CBF-1 mouse

    International Nuclear Information System (INIS)

    Saito, M.; Kindel, G.; Karczmar, A.G.; Rosenberg, A.

    1986-01-01

    In order to quantify the changes that occur in the cholinergic central nervous system with aging, we have compared acetylcholine (Ach) formation in brain cortex slice preparations from 2-year-old aged CBF-1 mouse brains and compared the findings with those in 2-4-month-old young adult mouse brain slices. Incorporation of exogenous radioactively labelled choline (31 nM [ 3 H] choline) into acetyl choline in incubated brain slices was linear with time for 90 min. Percentage of total choline label distributed into Ach remained constant from 5 min after starting the incubation to 90 min. In contrast, distribution of label into intracellular free choline (Ch) and phosphorylcholine (Pch) changed continuously over this period suggesting that the Ch pool for Ach synthesis in brain cortex is different from that for Pch synthesis. Incorporation of radioactivity into Ach was not influenced by administration of 10 microM eserine, showing that the increment of radioactivity in Ach reflects rate of Ach formation, independently from degradation by acetylcholine esterases. Under our experimental conditions, slices from cortices of aged 24-month-old mouse brain showed a significantly greater (27%) incorporation of radioactivity into intracellular Ach than those from young, 2-4-month-old, brain cortices. Inhibitors of Ach release, 1 mM ATP or GABA, had no effect. Since concentration of radioactive precursor in the incubation medium was very low (31 nM), the Ch pool for Ach synthesis in slices was labelled without measurably changing the size of the endogenous pool. These data suggest a compensatory acceleration of Ach synthesis or else a smaller precursor pool specific for Ach synthesis into which labelled Ch migrated in aged brain

  10. Genetic signatures in choline and 1-carbon metabolism are associated with the severity of hepatic steatosis

    Science.gov (United States)

    Corbin, Karen D.; Abdelmalek, Manal F.; Spencer, Melanie D.; da Costa, Kerry-Ann; Galanko, Joseph A.; Sha, Wei; Suzuki, Ayako; Guy, Cynthia D.; Cardona, Diana M.; Torquati, Alfonso; Diehl, Anna Mae; Zeisel, Steven H.

    2013-01-01

    Choline metabolism is important for very low-density lipoprotein secretion, making this nutritional pathway an important contributor to hepatic lipid balance. The purpose of this study was to assess whether the cumulative effects of multiple single nucleotide polymorphisms (SNPs) across genes of choline/1-carbon metabolism and functionally related pathways increase susceptibility to developing hepatic steatosis. In biopsy-characterized cases of nonalcoholic fatty liver disease and controls, we assessed 260 SNPs across 21 genes in choline/1-carbon metabolism. When SNPs were examined individually, using logistic regression, we only identified a single SNP (PNPLA3 rs738409) that was significantly associated with severity of hepatic steatosis after adjusting for confounders and multiple comparisons (P=0.02). However, when groupings of SNPs in similar metabolic pathways were defined using unsupervised hierarchical clustering, we identified groups of subjects with shared SNP signatures that were significantly correlated with steatosis burden (P=0.0002). The lowest and highest steatosis clusters could also be differentiated by ethnicity. However, unique SNP patterns defined steatosis burden irrespective of ethnicity. Our results suggest that analysis of SNP patterns in genes of choline/1-carbon metabolism may be useful for prediction of severity of steatosis in specific subsets of people, and the metabolic inefficiencies caused by these SNPs should be examined further.—Corbin, K. D., Abdelmalek, M. F., Spencer, M. D., da Costa, K.-A., Galanko, J. A., Sha, W., Suzuki, A., Guy, C. D., Cardona, D. M., Torquati, A., Diehl, A. M., Zeisel, S. H. Genetic signatures in choline and 1-carbon metabolism are associated with the severity of hepatic steatosis. PMID:23292069

  11. Radiosynthesis and pre-clinical evaluation of [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Graham [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Zhao Yongjun [MDx Discovery (part of GE Healthcare) at Hammersmith Imanet, Ltd., Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Leyton, Julius [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Shan Bo [MDx Discovery (part of GE Healthcare) at Hammersmith Imanet, Ltd., Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Nguyen, Quang-de; Perumal, Meg [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Turton, David [GE-Imanet, Hammersmith Hospital, Du Cane Road, London, W12 0NN (United Kingdom); Arstad, Erik; Luthra, Sajinder K.; Robins, Edward G. [MDx Discovery (part of GE Healthcare) at Hammersmith Imanet, Ltd., Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Aboagye, Eric O., E-mail: eric.aboagye@imperial.ac.u [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom)

    2011-01-15

    Introduction: Choline radiotracers are widely used for clinical PET diagnosis in oncology. [{sup 11}C]Choline finds particular utility in the imaging of brain and prostate tumor metabolic status, where 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ('FDG') shows high background uptake. More recently we have extended the clinical utility of [{sup 11}C]choline to breast cancer where radiotracer uptake correlates with tumor aggressiveness (grade). In the present study, a new choline analog, [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline, was synthesized and evaluated as a potential PET imaging probe. Methods: [{sup 18}F]Fluorocholine, [{sup 18}F]fluoro-[1-{sup 2}H{sub 2}]choline and [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline were synthesized by alkylation of the relevant precursor with [{sup 18}F]fluorobromomethane or [{sup 18}F]fluoromethyl tosylate. Radiosynthesis of [{sup 18}F]fluoromethyl tosylate required extensive modification of the existing method. [{sup 18}F]Fluorocholine and [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline were then subjected to in vitro oxidative stability analysis in a chemical oxidation model using potassium permanganate and an enzymatic model using choline oxidase. The two radiotracers, together with the corresponding di-deuterated compound, [{sup 18}F]fluoro-[1-{sup 2}H{sub 2}]choline, were then evaluated in vivo in a time-course biodistribution study in HCT-116 tumor-bearing mice. Results: Alkylation with [{sup 18}F]fluoromethyl tosylate proved to be the most reliable radiosynthetic route. Stability models indicate that [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline possesses increased chemical and enzymatic (choline oxidase) oxidative stability relative to [{sup 18}F]fluorocholine. The distribution of the three radiotracers, [{sup 18}F]fluorocholine, [{sup 18}F]fluoro-[1-{sup 2}H{sub 2}]choline and [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline, showed a similar uptake profile in most organs. Crucially, tumor uptake of [{sup 18}F

  12. Crystal structure of CbpF, a bifunctional choline-binding protein and autolysis regulator from Streptococcus pneumoniae.

    Science.gov (United States)

    Molina, Rafael; González, Ana; Stelter, Meike; Pérez-Dorado, Inmaculada; Kahn, Richard; Morales, María; Moscoso, Miriam; Campuzano, Susana; Campillo, Nuria E; Mobashery, Shahriar; García, José L; García, Pedro; Hermoso, Juan A

    2009-03-01

    Phosphorylcholine, a crucial component of the pneumococcal cell wall, is essential in bacterial physiology and in human pathogenesis because it binds to serum components of the immune system and acts as a docking station for the family of surface choline-binding proteins. The three-dimensional structure of choline-binding protein F (CbpF), one of the most abundant proteins in the pneumococcal cell wall, has been solved in complex with choline. CbpF shows a new modular structure composed both of consensus and non-consensus choline-binding repeats, distributed along its length, which markedly alter its shape, charge distribution and binding ability, and organizing the protein into two well-defined modules. The carboxy-terminal module is involved in cell wall binding and the amino-terminal module is crucial for inhibition of the autolytic LytC muramidase, providing a regulatory function for pneumococcal autolysis.

  13. Choline PET based dose-painting in prostate cancer - Modelling of dose effects

    International Nuclear Information System (INIS)

    Niyazi, Maximilian; Bartenstein, Peter; Belka, Claus; Ganswindt, Ute

    2010-01-01

    Several randomized trials have documented the value of radiation dose escalation in patients with prostate cancer, especially in patients with intermediate risk profile. Up to now dose escalation is usually applied to the whole prostate. IMRT and related techniques currently allow for dose escalation in sub-volumes of the organ. However, the sensitivity of the imaging modality and the fact that small islands of cancer are often dispersed within the whole organ may limit these approaches with regard to a clear clinical benefit. In order to assess potential effects of a dose escalation in certain sub-volumes based on choline PET imaging a mathematical dose-response model was developed. Based on different assumptions for α/β, γ50, sensitivity and specificity of choline PET, the influence of the whole prostate and simultaneous integrated boost (SIB) dose on tumor control probability (TCP) was calculated. Based on the given heterogeneity of all potential variables certain representative permutations of the parameters were chosen and, subsequently, the influence on TCP was assessed. Using schedules with 74 Gy within the whole prostate and a SIB dose of 90 Gy the TCP increase ranged from 23.1% (high detection rate of choline PET, low whole prostate dose, high γ50/ASTRO definition for tumor control) to 1.4% TCP gain (low sensitivity of PET, high whole prostate dose, CN + 2 definition for tumor control) or even 0% in selected cases. The corresponding initial TCP values without integrated boost ranged from 67.3% to 100%. According to a large data set of intermediate-risk prostate cancer patients the resulting TCP gains ranged from 22.2% to 10.1% (ASTRO definition) or from 13.2% to 6.0% (CN + 2 definition). Although a simplified mathematical model was employed, the presented model allows for an estimation in how far given schedules are relevant for clinical practice. However, the benefit of a SIB based on choline PET seems less than intuitively expected. Only under the

  14. Four-week dietary supplementation with 10- and/or 15-fold basal choline caused decreased body weight in Sprague Dawley rats.

    Science.gov (United States)

    Bagley, Bradford D; Chang, Shu-Ching; Ehresman, David J; Eveland, Alan; Parker, George A; Peters, Jeffrey M; Butenhoff, John L

    2017-10-01

    Choline is an essential nutrient utilized for phosphatidylcholine biosynthesis and lipoprotein packaging and secretion. Recently, choline supplementation has been used by athletes and the public for weight loss. However, the potential toxicological impact of choline dietary supplementation requires further investigation. This study examined the effects of choline dietary supplementation in Sprague Dawley rats for 4 weeks. Rats were fed diets containing basal choline levels (control) or 5-, 10-, or 15-fold (5×, 10×, or 15×) basal diet concentration. In groups fed choline-supplemented diets, there were no toxicologically relevant findings in clinical observations, food intake, clinical chemistry, liver weights, or liver histopathology. However, decreased mean body weights (8.5-10.2%) and body weight gains (24-31%) were noted for the 10× choline-supplemented (females only) and 15× choline-supplemented (both sexes) groups relative to the control groups from day 3 onward. These body weight effects were not related to a persistent reduction in average food intake. Serum cholesterol was increased in the 15× choline-supplemented male rats relative to the controls, an expected effect of choline supplementation; however, there were no changes in the serum cholesterol of female rats. Serum choline concentrations were increased in female rats relative to the male rats across all treatment groups. The maximum tolerated dose for male and female rats were the 15× and 10× choline supplements, respectively, based on decreased mean body weight and body weight gains. This study supported the conclusions of a clinical trial that showed a high choline diet can decrease body weight in humans.

  15. Long-term effects on biotransformation of labelled choline in different parts of the rat brain induced by single choline injections

    Energy Technology Data Exchange (ETDEWEB)

    Nordberg, A.; Wahlstroem, G.

    1988-01-01

    The long-term effects of single choline (Ch) injections on the uptake and metabolism of a tracer dose of /sup 3/H-Ch were studied in male rats. Choline was administered as a threshold infusion to obtain convulsions 10 and 4 weeks before sacrific (group 1). At a single threshold infusion of choline 4 weeks before sacrifice no convulsions were induced in 50% of the animals in a second group (group 2-) whereas convulsions were induced in the remainder of the animals in this group (group 2+). Group 3 contained control animals. One min. after administration of a tracer dose of /sup 3/H-Ch the animals were sacrificed and examined for /sup 3/H-total activity, /sup 3/H-Ch, /sup 3/H-acetylcholine (/sup 3/H-ACh) and /sup 3/H-phosphorylcholine (/sup 3/-H-PhCh). These activities were determined in three parts of the brain (cortex, striatum, midbrain + medulla oblongata). In the cortex a significant negative correlation between brain weight and /sup 3/H-ACh synthesis was seen in group 1. A comparison between group 2+ and group 2- indicated that induced convulsions were not critical for this effect. In the striatum there was a significant reduction in the total uptake of radioactivity in group 1 and group 2- when values were compared to the control group. Furthermore a significant positive correlation was detected between the concentration of radiolabel and /sup 3/H-ACh synthesis and a negative relationship with the level of /sup 3/H-Ch. In the midbrain preparation the synthesis of /sup 3/H-ACh was reduced in group 1 where a significant negative correlation was found between the average threshold dose of choline and both /sup 3/H-Ach and /sup 3/H-PhCh synthesis. Thus the Ch threshold doses given several weeks before testing seem to have long term effects on the uptake and utilization of a tracer dose of /sup 3/H-Ch in the cortex and striatum.

  16. Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice

    International Nuclear Information System (INIS)

    Zhang, Jianhai; Zhang, Yufang; Liang, Chen; Wang, Nasui; Zheng, Heping; Wang, Jundong

    2016-01-01

    Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150 mg/L NaF in drinking water, 5.75 g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15 weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. - Highlights: • Fluoride exposure altered the growth and development, sperm count and sperm survival percentages, testicular histology • Fluoride exposure decreased NGF, Ras, and Mek mRNA and NGF and p-MEK protein expressions in testis of mice. • Choline supplementation diminishes fluoride-induced testicular toxicity.

  17. Perfluorooctane Sulfonate-Induced Hepatic Steatosis in Male Sprague Dawley Rats Is Not Attenuated by Dietary Choline Supplementation.

    Science.gov (United States)

    Bagley, Bradford D; Chang, Shu-Ching; Ehresman, David J; Eveland, Alan; Zitzow, Jeremiah D; Parker, George A; Peters, Jeffrey M; Wallace, Kendall B; Butenhoff, John L

    2017-12-01

    Perfluorooctane sulfonate (PFOS) is an environmentally persistent chemical. Dietary 100 ppm PFOS fed to male mice and rats for 4 weeks caused hepatic steatosis through an unknown mechanism. Choline deficient diets can cause hepatic steatosis. A hepatic choline:PFOS ion complex was hypothesized to cause this effect in mice. This study tested whether dietary choline supplementation attenuates PFOS-induced hepatic steatosis in rats. Sprague Dawley rats (12/sex/group) were fed control, choline supplemented (CS), 100 ppm PFOS, or 100 ppm PFOS + CS diets for 3 weeks. Male rats fed both PFOS-containing diets had decreased serum cholesterol and triglycerides (TGs) on days 9, 16, and/or 23 and increased hepatic free fatty acids and TG (ie, steatosis). Female rats fed both PFOS diets had decreased serum cholesterol on days 9 and 16 and decreased hepatic free fatty acid and TG at termination (ie, no steatosis). Liver PFOS concentrations were similar for both sexes. Liver choline concentrations were increased in male rats fed PFOS (±CS), but the increase was lower in the PFOS + CS group. Female liver choline concentrations were not altered by any diet. These findings demonstrate a clear sex-related difference in PFOS-induced hepatic steatosis in the rat. Additional evaluated mechanisms (ie, nuclear receptor activation, mRNA upregulation, and choline kinase activity inhibition) did not appear to be involved in the hepatic steatosis. Dietary PFOS (100 ppm) induced hepatic steatosis in male, but not female, rats that was not attenuated by choline supplementation. The mechanism of lipid accumulation and the sex-related differences warrant further investigation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jianhai [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China); Zhang, Yufang [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China); Veterinary Station in Chen Villages of Lin Country, Linxian, Shanxi 033200 (China); Liang, Chen [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China); Wang, Nasui [Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia, Charlottesville, VA 22908 (United States); Division of Endocrinology and Metabolism, Department of Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou (China); Zheng, Heping [Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908 (United States); Wang, Jundong, E-mail: wangjd53@outlook.com [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China)

    2016-11-01

    Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150 mg/L NaF in drinking water, 5.75 g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15 weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. - Highlights: • Fluoride exposure altered the growth and development, sperm count and sperm survival percentages, testicular histology • Fluoride exposure decreased NGF, Ras, and Mek mRNA and NGF and p-MEK protein expressions in testis of mice. • Choline supplementation diminishes fluoride-induced testicular toxicity.

  19. Verbal and visual memory improve after choline supplementation in long-term total parenteral nutrition: a pilot study.

    Science.gov (United States)

    Buchman, A L; Sohel, M; Brown, M; Jenden, D J; Ahn, C; Roch, M; Brawley, T L

    2001-01-01

    Previous investigations have demonstrated that choline deficiency, manifested in low plasma-free choline concentration and hepatic injury, may develop in patients who require long-term total parenteral nutrition (TPN). Preliminary studies have suggested lecithin or choline supplementation might lead to improved visual memory in the elderly and reverse abnormal neuropsychological development in children. We sought to determine if choline-supplemented TPN would lead to improvement in neuropsychological test scores in a group of adult, choline-deficient outpatients receiving TPN. Eleven subjects (8 males, 3 females) who received nightly TPN for more than 80% of their nutritional needs for at least 12 weeks before entry in the study were enrolled. Exclusion criteria included active drug abuse, mental retardation, cerebral vascular accident, head trauma, hemodialysis or peritoneal dialysis, (prothrombin time [PT] >2x control), or acquired immune deficiency syndrome (AIDS). Patients were randomly assigned to receive their usual TPN regimen (n = 6, aged 34.0 +/- 12.6 years) over a 12-hour nightly infusion or their usual TPN regimen plus choline chloride (2 g) (n = 5, aged 37.3 +/- 7.3 years). The following neuropsychological tests were administered at baseline and after 24 weeks of choline supplementation (or placebo): Weschler Adult Intelligence Scale-Revised (WAIS-R, intellectual functioning), Weschler Memory Scale-Revised (WMS-R, two subtests, verbal and visual memory), Rey-Osterrieth Complex Figure Test (visuospatial functioning and perceptual organization), Controlled Oral Word Association Test (verbal fluency), Grooved Pegboard (manual dexterity and motor speed), California Verbal Learning Test (CVLT, rote verbal learning ability), and Trail Making Parts A & B (visual scanning, psychomotor speed and set shifting). Scores were reported in terms of standard scores including z scores and percentile ranks. Mean absolute changes in raw scores were compared between groups

  20. Choline and/or folic acid deficiency is associated with genomic damage and cell death in human lymphocytes in vitro.

    Science.gov (United States)

    Lu, Lin; Ni, Juan; Zhou, Tao; Xu, Weijiang; Fenech, Michael; Wang, Xu

    2012-04-01

    Choline and folate are interrelated methyl donors. Previous studies showed that folate prevents genomic damage in human lymphocytes in vitro; however, the association between choline and human genomic stability is uncertain. To explore the genotoxicity, cytotoxicity, and cytostatic effects and possible interactions of choline and/or folate deficiency on the human genome, lymphocytes from 6 volunteers were cultured in 18 combinations of choline (CC) and folic acid (FA) media for 9 days. The genotoxicity was evaluated by micronuclei, nucleoplasmic bridges, and nuclear buds in the binucleated cell; the cytotoxicity indices included apoptosis and necrosis, and the cytostatic effects were indicated by nuclear division index (NDI). Across all choline concentrations, the frequencies of all biomarkers except NDI were diminished when FA concentration was more than or equal to 120 nmol/L. The frequencies of micronuclei, buds, and necrosis were significantly higher at lower levels of CC (0-6 μmol/L) compared with higher concentrations of CC (12-21.5 μmol/L) while maintaining the same FA concentration. We concluded that both choline and folate significantly impact genomic stability and cell death, although effects of folate were 2.5- to 6.2-fold greater, depending on the biomarker and dose. A combination of 12 μmol/L CC and 120 nmol/L FA appears to be optimal for genomic integrity in vitro.

  1. Effect of choline supplementation on rapid weight loss and biochemical variables among female taekwondo and judo athletes.

    Science.gov (United States)

    Elsawy, Gehan; Abdelrahman, Osama; Hamza, Amr

    2014-03-27

    Taekwondo and judo competitions are divided into weight categories. Many athletes reduce their body mass a few days before competition in order to obtain a competitive advantage over lighter opponents. To achieve fast body mass reduction, athletes use a number of nutritional strategies, including choline supplementation. The goal of this study was to identify the effects of choline supplementation on body mass reduction and leptin levels among female taekwondo and judo athletes. Twenty-two female athletes (15 taekwondo and 7 judo athletes) were selected from different weight categories and divided into two groups, according to weight. The players in the experimental group took choline tablets for one week before a competition. The results revealed significant differences between pre- and post-competition measurements of leptin, free plasma choline, urine choline and urine malondialdehyde levels; body mass was also reduced in the post-competition measurements. In conclusion, choline supplementation could rapidly reduce body mass without any side effects on biochemical levels or static strength.

  2. Uptake of 3H-choline and synthesis of 3H-acetylcholine by human penile corpus cavernosum

    International Nuclear Information System (INIS)

    Blanco, R.; Saenz de Tejada, I.; Azadzoi, K.; Goldstein, I.; Krane, R.J.; Wotiz, H.H.; Cohen, R.A.

    1986-01-01

    The neuroeffectors which relax penile smooth muscle and lead to erection are unknown; physiological studies of human corpus cavernosum, in vitro, have suggested a significant role of cholinergic neurotransmission. To further characterize the importance of cholinergic nerves, biopsies of human corpus cavernosum were obtained at the time of penile prosthesis implantation. Tissues were incubated in 3 H-choline (10 -5 M, 80 Ci/mmol) in oxygenated physiological salt solution at 37 0 C, pH 7.4 for 1 hour. Radiolabelled compounds were extracted with perchloric acid (0.4 M) and acetylcholine and choline were separated by HPLC; 14 C-acetylcholine was used as internal standard. 3 H-choline was accumulated by the tissues (20 +/- 1.9 fmol/mg), and 3 H-acetylcholine was synthesized (4.0 +/- 1.1 fmol/mg). In control experiments, heating of the tissue blocked synthesis of 3 H-acetylcholine. Inhibition of high affinity choline transport by hemicholinium-3 (10 -5 M) diminished tissue accumulation of 3 H-choline and significantly reduced the synthesis of 3 H-acetylcholine (0.5 +/ 0.2 fmol/mg, p < 0.05). These results provide direct evidence of neuronal accumulation of choline and enzymatic conversion to acetylcholine in human corpus cavernosum. Taken together with the physiological studies, it can be concluded that cholinergic neurotransmission in human corpus cavernosum plays a role in penile erection

  3. Usefulness of Choline-PET for the detection of residual hemangiopericytoma in the skull base: comparison with FDG-PET

    Directory of Open Access Journals (Sweden)

    Ito Shin

    2012-02-01

    Full Text Available Abstract Background Choline is a new PET tracer that is useful for the detection of malignant tumor. Choline is a precursor of the biosynthesis of phosphatidylcholine, a major phospholipid in the cell membrane of eukaryotic cells. Malignant tumors have an elevated level of phosphatidylcholine in cell membrane. Thus, choline is a marker of tumor malignancy. Method The patient was a 51-year-old man with repeated recurrent hemangiopericytoma in the skull base. We performed Choline-PET in this patient after various treatments and compared findings with those of FDG-PET. Results Choline accumulated in this tumor, but FDG did not accumulate. We diagnosed this tumor as residual hemangiopericytoma and performed the resection of the residual tumor. FDG-PET is not appropriate for skull base tumor detection because uptake in the brain is very strong. Conclusion We emphasize the usefulness of Choline-PET for the detection of residual hemangiopericytoma in the skull base after various treatments, compared with FDG-PET.

  4. Acetylcholine and choline contents of rat skeletal muscle determined by a radioenzymatic microassay: effects of drugs

    International Nuclear Information System (INIS)

    Consolo, S.

    1986-01-01

    This paper describes a specific, radioenzymatic microassay for measuring picomole quantities of ACh in skeletal muscle. The levels of ACh as well ascholine in the extensor digitorum longus (EDL), soleus and gastrocnemiusmuscles of the rat are reported after focussed microwave irradiation to the hind limb to prevent post-mortem changes in ACh and choline contents. Particular attention was directed to the effect of some drugs potently affecting neuromuscular transmission at the end plate. Preparation of tissue samples, extraction and electrophoresis are described. A 26 ul portion of a second incubation mixture of tritium-acetylcoenzyme A and 14 ul of a partially purified choline acetyltransferase solution were added. A flow sheet giving an overview of he analytical steps involved in the method are shown

  5. Choline uptake in the hippocampus: inhibition of septal-hippocampal cholinergenic neurons by intraventricular barbiturates

    International Nuclear Information System (INIS)

    Richter, J.A.

    1986-01-01

    The author attempts to determine where in the brain pentobarbital acts to cause the inhibition of high-affinity, sodium-dependent choline uptake, and what behavioral consequences result from this particular effect of barbituates. The experiments were done in male Wistar rats which had received an injection of Nivea cream injected directly to the acannula. In the experiments the drug solution injected into the lateral ventricle was also spiked with ( 14 C) - phenobarbital at a final specific activity of 5 dpm/nmole so that a more precise estimate of the spread of drug solution could be made. When a phenobarbital-Fast green Dye mixture was injected bilaterally into the lateral ventricles, the dye was found to have spread through the entire ventricular system when the rat was killed 10-20 min later. Choline uptake in the hippocampus was inhibited and the inhibition was apparently greater of 20 min rather than 10 min were allowed to elapse after the injection

  6. Choline and Working Memory Training Improve Cognitive Deficits Caused by Prenatal Exposure to Ethanol

    Directory of Open Access Journals (Sweden)

    Jaylyn Waddell

    2017-09-01

    Full Text Available Prenatal ethanol exposure is associated with deficits in executive function such as working memory, reversal learning and attentional set shifting in humans and animals. These behaviors are dependent on normal structure and function in cholinergic brain regions. Supplementation with choline can improve many behaviors in rodent models of fetal alcohol spectrum disorders and also improves working memory function in normal rats. We tested the hypothesis that supplementation with choline in the postnatal period will improve working memory during adolescence in normal and ethanol-exposed animals, and that working memory engagement during adolescence will transfer to other cognitive domains and have lasting effects on executive function in adulthood. Male and female offspring of rats fed an ethanol-containing liquid diet (ET; 3% v/v or control dams given a non-ethanol liquid diet (CT were injected with choline (Cho; 100 mg/kg or saline (Sal once per day from postnatal day (P 16–P30. Animals were trained/tested on a working memory test in adolescence and then underwent attentional set shifting and reversal learning in young adulthood. In adolescence, ET rats required more training to reach criterion than CT-Sal. Choline improved working memory performance for both CT and ET animals. In young adulthood, ET animals also performed poorly on the set shifting and reversal tasks. Deficits were more robust in ET male rats than female ET rats, but Cho improved performance in both sexes. ET male rats given a combination of Cho and working memory training in adolescence required significantly fewer trials to achieve criterion than any other ET group, suggesting that early interventions can cause a persistent improvement.

  7. 11C-Choline PET/pathology image coregistration in primary localized prostate cancer

    International Nuclear Information System (INIS)

    Grosu, Anca-Ligia; Prokic, Vesna; Weirich, Gregor; Wendl, Christina; Geinitz, Hans; Molls, Michael; Kirste, Simon; Souvatzoglou, Michael; Schwaiger, Markus; Gschwend, Juergen E.; Treiber, Uwe; Weber, Wolfgang A.; Krause, Bernd Joachim

    2014-01-01

    The aim of this study was to develop a methodology for the comparison of pathology specimens after prostatectomy (post-S) with PET images obtained before surgery (pre-S). This method was used to evaluate the merit of 11 C-choline PET/CT for delineation of gross tumour volume (GTV) in prostate cancer (PC). In 28 PC patients, 11 C-choline PET/CT was performed before surgery. PET/CT data were coregistered with the pathology specimens. GTV on PET images (GTV-PET) was outlined automatically and corrected manually. Tumour volume in the prostate (TVP) was delineated manually on the pathology specimens. Based on the coregistered PET/pathology images, the following parameters were assessed: SUVmax and SUVmean in the tumoral and nontumoral prostate (NP), GTV-PET (millilitres) and TVP (millilitres). PET/pathology image coregistration was satisfactory. Mean SUVmax in the TVP was lower than in the NP: 5.0 and 5.5, respectively (p = 0.093). Considering the entire prostate, SUVmax was located in the TVP in two patients, in the TVP and NP in 12 patients and exclusively in NP in 14 patients. Partial overlap the TVP and GTV-PET was seen in 71 % of patients, and complete overlap in 4 %. PET/pathology image coregistration can be used for evaluation of different imaging modalities. 11 C-Choline PET failed to distinguish tumour from nontumour tissue. (orig.)

  8. Choline Modulation of the Aβ P1-40 Channel Reconstituted into a Model Lipid Membrane

    Directory of Open Access Journals (Sweden)

    Daniela Meleleo

    2010-01-01

    Full Text Available Nicotinic acetylcholine receptors (AChRs, implicated in memory and learning, in subjects affected by Alzheimer's disease result altered. Stimulation of α7-nAChRs inhibits amyloid plaques and increases ACh release. β-amyloid peptide (AβP forms ion channels in the cell and model phospholipid membranes that are retained responsible in Alzheimer disease. We tested if choline, precursor of ACh, could affect the AβP1-40 channels in oxidized cholesterol (OxCh and in palmitoyl-oleoyl-phosphatidylcholine (POPC:Ch lipid bilayers. Choline concentrations of 5 × 10−11 M–1.5 × 10−8 M added to the cis- or trans-side of membrane quickly increased AβP1-40 ion channel frequency (events/min and ion conductance in OxCh membranes, but not in POPC:Ch membranes. Circular Dichroism (CD spectroscopy shows that after 24 and 48 hours of incubation with AβP1-40, choline stabilizes the random coil conformation of the peptide, making it less prone to fibrillate. These actions seem to be specific in that ACh is ineffective either in solution or on AβP1-40 channel incorporated into PLMs.

  9. The use of choline in association with the Bangerter filters for the treatment of amblyopia

    Directory of Open Access Journals (Sweden)

    Lelio Sabetti

    2017-11-01

    Full Text Available The study investigated the effects of choline combined with Bangerter filter in the treatment of amblyopia. All amblyopic subjects used a Bangerter filter on the corrective spectacle lens (1d over the left eye, 1d over the right eye. Choline was then administered orally to 39 patients once daily, five days per week for the entire study period. Subjects treated with the Bangerter filter showed a mean visual acuity of 0.27 logMAR; at 12mo of treatment, the mean visual acuity reached 0.09 logMAR. Patients treated with the Bangerter filter and citicoline showed a mean visual acuity of 0.35 logMAR; at 12mo of treatment, the mean visual acuity reached 0.01 logMAR. No significant changes in the angle of deviation were observed in both groups. Subjects in both forms of amblyopia therapies demonstrated an increase in visual acuity. However, these effects were markedly enhanced when coupled with the administration of choline. Findings suggest that the effects are particularly relevant in the more severe amblyopic cases.

  10. Choline-Deficient-Diet-Induced Fatty Liver Is a Metastasis-Resistant Microenvironment.

    Science.gov (United States)

    Nakamura, Miki; Suetsugu, Atsushi; Hasegawa, Kosuke; Matsumoto, Takuro; Aoki, Hitomi; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Hoffman, Robert M

    2017-07-01

    Fatty liver disease is increasing in the developed and developing world. Liver metastasis from malignant lymphoma in the fatty liver is poorly understood. In a previous report, we developed color-coded imaging of the tumor microenvironment (TME) of the murine EL4-RFP malignant lymphoma during metastasis, including the lung. In the present report, we investigated the potential and microenvironment of the fatty liver induced by a choline-deficient diet as a metastatic site in this mouse lymphoma model. C57BL/6-GFP transgenic mice were fed with a choline-deficient diet in order to establish a fatty liver model. EL4-RFP cells were injected in the spleen of normal mice and fatty-liver mice. Metastases in mice with fatty liver or normal liver were imaged with the Olympus SZX7 microscope and the Olympus FV1000 confocal microscope. Metastases of EL4-RFP were observed in the liver, ascites and bone marrow. Primary tumors were imaged in the spleen at the injection site. The fewest metastases were observed in the fatty liver. In addition, the fewest cancer-associated fibroblasts (CAFs) were observed in the fatty liver. The relative metastatic resistance of the fatty liver may be due to the reduced number of CAFs in the fatty livers. The mechanism of the effect of the choline-deficient diet is discussed. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Value of {sup 11}C-choline PET and PET/CT in patients with suspected prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Scher, Bernhard; Albinger, Wolfram; Tiling, Reinhold; Gildehaus, Franz-Josef; Dresel, Stefan [University of Munich, Department of Nuclear Medicine, Munich (Germany); Seitz, Michael [University of Munich, Department of Urology, Munich (Germany); Scherr, Michael; Becker, Hans-Christoph [University of Munich, Department of Radiology, Munich (Germany); Souvatzogluou, Michael; Wester, Hans-Juergen [Technical University of Munich, Department of Nuclear Medicine, Munich (Germany)

    2007-01-15

    The value and limitations of {sup 11}C-choline PET and PET/CT for the detection of prostate cancer remain controversial. The aim of this study was to investigate the diagnostic efficacy of {sup 11}C-choline PET and PET/CT in a large group of patients with suspected prostate cancer. Fifty-eight patients with clinical suspicion of prostate cancer underwent {sup 11}C-choline PET (25/58, Siemens ECAT Exact HR+) or PET/CT (33/58, Philips Gemini) scanning. On average, 500 MBq of {sup 11}C-choline was administered intravenously. Studies were interpreted by raters blinded to clinical information and other diagnostic procedures. Qualitative image analysis as well as semiquantitative SUV measurement was carried out. The reference standard was histopathological examination of resection specimens or biopsy. Prevalence of prostate cancer in this selected patient population was 63.8% (37/58). {sup 11}C-choline PET and PET/CT showed a sensitivity of 86.5% (32/37) and a specificity of 61.9% (13/21) in the detection of the primary malignancy. With regard to metastatic spread, PET showed a per-patient sensitivity of 81.8% (9/11) and produced no false positive findings. Based on our findings, differentiation between benign prostatic changes, such as benign prostatic hyperplasia or prostatitis, and prostate cancer is feasible in the majority of cases when image interpretation is primarily based on qualitative characteristics. SUV{sub max} may serve as guidance. False positive findings may occur due to an overlap of {sup 11}C-choline uptake between benign and malignant processes. By providing functional information regarding both the primary malignancy and its metastases, {sup 11}C-choline PET may prove to be a useful method for staging prostate cancer. (orig.)

  12. Choline status and neurodevelopmental outcomes at 5 years of age in the Seychelles Child Development Nutrition Study.

    Science.gov (United States)

    Strain, J J; McSorley, Emeir M; van Wijngaarden, Edwin; Kobrosly, Roni W; Bonham, Maxine P; Mulhern, Maria S; McAfee, Alison J; Davidson, Philip W; Shamlaye, Conrad F; Henderson, Juliette; Watson, Gene E; Thurston, Sally W; Wallace, Julie M W; Ueland, Per M; Myers, Gary J

    2013-07-28

    Choline is an essential nutrient that is found in many food sources and plays a critical role in the development of the central nervous system. Animal studies have shown that choline status pre- and postnatally can have long-lasting effects on attention and memory; however, effects in human subjects have not been well studied. The aim of the present study was to examine the association between plasma concentrations of free choline and its related metabolites in children and their neurodevelopment in the Seychelles Child Development Nutrition Study, an ongoing longitudinal study assessing the development of children born to mothers with high fish consumption during pregnancy. Plasma concentrations of free choline, betaine, dimethylglycine (DMG), methionine and homocysteine and specific measures of neurodevelopment were measured in 210 children aged 5 years. The children's plasma free choline concentration (9·17 (sd 2·09) μmol/l) was moderately, but significantly, correlated with betaine (r 0·24; P= 0·0006), DMG (r 0·15; P= 0·03), methionine (r 0·24; P= 0·0005) and homocysteine (r 0·19; P= 0·006) concentrations. Adjusted multiple linear regression revealed that betaine concentrations were positively associated with Preschool Language Scale – total language scores (β = 0·066; P= 0·04), but no other associations were evident. We found no indication that free choline concentration or its metabolites, within the normal physiological range, are associated with neurodevelopmental outcomes in children at 5 years of age. As there is considerable animal evidence suggesting that choline status during development is associated with cognitive outcome, the issue deserves further study in other cohorts.

  13. Ocular lesions and experimental choline deficiency Lesiones oculares y deficiencia experimental de colina

    Directory of Open Access Journals (Sweden)

    Georgina P. Ossani

    2006-10-01

    Full Text Available Previous studies have shown ocular haemorrhages in choline-deficient rats. The aim of this paper is to study further the relationship between ocular and renal lesions and biochemical alterations in rats fed a choline-deficient diet. Fifty one weanling male Wistar rats, were divided into two groups. Thirty one of them were fed a choline-deficient diet and the rest was fed a choline-supplemented diet ad libitum. Animals from both groups were killed between the fifth and the eighth day. Urea, creatinine and homocysteine concentrations in blood were determined. Eyes were used for light microscopy study; high resolution light microscopy and the study of the retina as "rétine a plat". Kidneys were studied by light microscopy. Choline-supplemented rats did not show ocular or renal lesion. Choline-deficient rats that showed renal lesions, tubular or cortical necrosis, did not always have ocular changes. There were no ocular changes in the only choline-deficient rat without renal lesion. The ocular changes consisted mainly in haemorrhage in both cameras and ciliary and vitreous bodies. Correlations between ocular and renal lesion (r=0.72, pEstudios previos han demostrado hemorragia ocular en ratas deficientes en colina. El objetivo de este trabajo es profundizar en la relación entre las alteraciones oculares, renales y bioquímicas en ratas deficientes en colina. Cincuenta y una ratas Wistar macho recién destetadas fueron divididas en dos grupos: treinta y una fueron alimentadas con una dieta colino deficiente y el resto con colina suplementada ad-libitum. Los animales de ambos grupos fueron sacrificados entre el quinto y el octavo día. Se midió la concentración de urea, creatinina y homocisteína en sangre. Los ojos fueron estudiados por microscopía de luz, microscopía óptica de alta resolución y para el estudio de la retina como retina plana. Los riñones fueron estudiados por microscopía de luz. Las ratas suplementadas con colina no

  14. Choline Catabolism in Burkholderia thailandensis Is Regulated by Multiple Glutamine Amidotransferase 1-Containing AraC Family Transcriptional Regulators.

    Science.gov (United States)

    Nock, Adam M; Wargo, Matthew J

    2016-09-15

    Burkholderia thailandensis is a soil-dwelling bacterium that shares many metabolic pathways with the ecologically similar, but evolutionarily distant, Pseudomonas aeruginosa Among the diverse nutrients it can utilize is choline, metabolizable to the osmoprotectant glycine betaine and subsequently catabolized as a source of carbon and nitrogen, similar to P. aeruginosa Orthologs of genes in the choline catabolic pathway in these two bacteria showed distinct differences in gene arrangement as well as an additional orthologous transcriptional regulator in B. thailandensis In this study, we showed that multiple glutamine amidotransferase 1 (GATase 1)-containing AraC family transcription regulators (GATRs) are involved in regulation of the B. thailandensis choline catabolic pathway (gbdR1, gbdR2, and souR). Using genetic analyses and sequencing the transcriptome in the presence and absence of choline, we identified the likely regulons of gbdR1 (BTH_II1869) and gbdR2 (BTH_II0968). We also identified a functional ortholog for P. aeruginosa souR, a GATR that regulates the metabolism of sarcosine to glycine. GbdR1 is absolutely required for expression of the choline catabolic locus, similar to P. aeruginosa GbdR, while GbdR2 is important to increase expression of the catabolic locus. Additionally, the B. thailandensis SouR ortholog (BTH_II0994) is required for catabolism of choline and its metabolites as carbon sources, whereas in P. aeruginosa, SouR function can by bypassed by GbdR. The strategy employed by B. thailandensis represents a distinct regulatory solution to control choline catabolism and thus provides both an evolutionary counterpoint and an experimental system to analyze the acquisition and regulation of this pathway during environmental growth and infection. Many proteobacteria that occupy similar environmental niches have horizontally acquired orthologous genes for metabolism of compounds useful in their shared environment. The arrangement and differential

  15. Structural studies on choline-carboxylate bio-ionic liquids by x-ray scattering and molecular dynamics.

    Science.gov (United States)

    Tanzi, Luana; Ramondo, Fabio; Caminiti, Ruggero; Campetella, Marco; Di Luca, Andrea; Gontrani, Lorenzo

    2015-09-21

    We report a X-ray diffraction and molecular dynamics study on three choline-based bio-ionic liquids, choline formate, [Ch] [For], choline propanoate, [Ch][Pro], and choline butanoate, [Ch][But]. For the first time, this class of ionic liquids has been investigated by X-ray diffraction. Experimental and theoretical structure factors have been compared for each term of the series. Local structural organization has been obtained from ab initio calculations through static models of isolated ion pairs and dynamic simulations of small portions of liquids through twelve, ten, and nine ion pairs for [Ch][For], [Ch][Pro], and [Ch][But], respectively. All the theoretical models indicate that cations and anions are connected by strong hydrogen bonding and form stable ion pairs in the liquid that are reminiscent of the static ab initio ion pairs. Different structural aspects may affect the radial distribution function, like the local structure of ion pairs and the conformation of choline. When small portions of liquids have been simulated by dynamic quantum chemical methods, some key structural features of the X-ray radial distribution function were well reproduced whereas the classical force fields here applied did not entirely reproduce all the observed structural features.

  16. Choline acetyltransferase expression during periods of behavioral activity and across natural sleep-wake states in the basal forebrain.

    Science.gov (United States)

    Greco, M A; McCarley, R W; Shiromani, P J

    1999-01-01

    The present study examined whether the expression of the messenger RNA encoding the protein responsible for acetylcholine synthesis is associated with sleep-wakefulness. Choline acetyltransferase messenger RNA levels were analysed using a semi-quantitative assay in which reverse transcription was coupled to complementary DNA amplification using the polymerase chain reaction. To examine the relationship between steady-state messenger RNA and behavioral activity, rats were killed during the day (4.00 p.m.) or night (4.00 a.m.), and tissue from the vertical and horizontal limbs of the diagonal bands of Broca was analysed. Choline acetyltransferase messenger RNA levels were higher during the day than during the night. The second study examined more closely the association between choline acetyltransferase messenger RNA levels and individual bouts of wakefulness, slow-wave sleep or rapid eye movement sleep. Choline acetyltransferase messenger RNA levels were low during wakefulness, intermediate in slow-wave sleep and high during rapid eye movement sleep. In contrast, protein activity, measured at a projection site of cholinergic neurons of the basal forebrain, was higher during wakefulness than during sleep. These findings suggest that choline acetyltransferase protein and messenger RNA levels exhibit an inverse relationship during sleep and wakefulness. The increased messenger RNA expression during sleep is consistent with a restorative function of sleep.

  17. Structural studies on choline-carboxylate bio-ionic liquids by x-ray scattering and molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Tanzi, Luana; Ramondo, Fabio, E-mail: fabio.ramondo@univaq.it [Department of Physical and Chemical Sciences, University of L’Aquila, Via Vetoio, L’Aquila I-67100 (Italy); Caminiti, Ruggero; Campetella, Marco; Di Luca, Andrea; Gontrani, Lorenzo, E-mail: lorenzo.gontrani@uniroma1.it [Department of Chemistry, University of Rome ‘La Sapienza’, P.le Aldo Moro 5, I-00185 Rome (Italy)

    2015-09-21

    We report a X-ray diffraction and molecular dynamics study on three choline-based bio-ionic liquids, choline formate, [Ch] [For], choline propanoate, [Ch][Pro], and choline butanoate, [Ch][But]. For the first time, this class of ionic liquids has been investigated by X-ray diffraction. Experimental and theoretical structure factors have been compared for each term of the series. Local structural organization has been obtained from ab initio calculations through static models of isolated ion pairs and dynamic simulations of small portions of liquids through twelve, ten, and nine ion pairs for [Ch][For], [Ch][Pro], and [Ch][But], respectively. All the theoretical models indicate that cations and anions are connected by strong hydrogen bonding and form stable ion pairs in the liquid that are reminiscent of the static ab initio ion pairs. Different structural aspects may affect the radial distribution function, like the local structure of ion pairs and the conformation of choline. When small portions of liquids have been simulated by dynamic quantum chemical methods, some key structural features of the X-ray radial distribution function were well reproduced whereas the classical force fields here applied did not entirely reproduce all the observed structural features.

  18. Structural studies on choline-carboxylate bio-ionic liquids by x-ray scattering and molecular dynamics

    International Nuclear Information System (INIS)

    Tanzi, Luana; Ramondo, Fabio; Caminiti, Ruggero; Campetella, Marco; Di Luca, Andrea; Gontrani, Lorenzo

    2015-01-01

    We report a X-ray diffraction and molecular dynamics study on three choline-based bio-ionic liquids, choline formate, [Ch] [For], choline propanoate, [Ch][Pro], and choline butanoate, [Ch][But]. For the first time, this class of ionic liquids has been investigated by X-ray diffraction. Experimental and theoretical structure factors have been compared for each term of the series. Local structural organization has been obtained from ab initio calculations through static models of isolated ion pairs and dynamic simulations of small portions of liquids through twelve, ten, and nine ion pairs for [Ch][For], [Ch][Pro], and [Ch][But], respectively. All the theoretical models indicate that cations and anions are connected by strong hydrogen bonding and form stable ion pairs in the liquid that are reminiscent of the static ab initio ion pairs. Different structural aspects may affect the radial distribution function, like the local structure of ion pairs and the conformation of choline. When small portions of liquids have been simulated by dynamic quantum chemical methods, some key structural features of the X-ray radial distribution function were well reproduced whereas the classical force fields here applied did not entirely reproduce all the observed structural features

  19. Prospective head-to-head comparison of 11C-choline-PET/MR and 11C-choline-PET/CT for restaging of biochemical recurrent prostate cancer

    International Nuclear Information System (INIS)

    Eiber, Matthias; Rauscher, Isabel; Souvatzoglou, Michael; Schwaiger, Markus; Maurer, Tobias; Holzapfel, Konstantin; Beer, Ambros J.

    2017-01-01

    Whole-body integrated 11 C-choline PET/MR might provide advantages compared to 11 C-choline PET/CT for restaging of prostate cancer (PC) due to the high soft-tissue contrast and the use of multiparametric MRI, especially for detection of local recurrence and bone metastases. Ninety-four patients with recurrent PC underwent a single-injection/dual-imaging protocol with contrast-enhanced PET/CT followed by fully diagnostic PET/MR. Imaging datasets were read separately by two reader teams (team 1 and 2) assessing the presence of local recurrence, lymph node and bone metastases in predefined regions using a five-point scale. Detection rates were calculated. The diagnostic performance of PET/CT vs. PET/MR was compared using ROC analysis. Inter-observer and inter-modality variability, radiation exposure, and mean imaging time were evaluated. Clinical follow-up, imaging, and/or histopathology served as standard of reference (SOR). Seventy-five patients qualified for the final image analysis. A total of 188 regions were regarded as positive: local recurrence in 37 patients, 87 regions with lymph node metastases, and 64 regions with bone metastases. Mean detection rate between both readers teams for PET/MR was 84.7% compared to 77.3% for PET/CT (p > 0.05). Local recurrence was identified significantly more often in PET/MR compared to PET/CT by team 1. Lymph node and bone metastases were identified significantly more often in PET/CT compared to PET/MR by both teams. However, this difference was not present in the subgroup of patients with PSA values ≤2 ng/ml. Inter-modality and inter-observer agreement (K > 0.6) was moderate to substantial for nearly all categories. Mean reduction of radiation exposure for PET/MR compared to PET/CT was 79.7% (range, 72.6-86.2%). Mean imaging time for PET/CT was substantially lower (18.4 ± 0.7 min) compared to PET/MR (50.4 ± 7.9 min). 11 C-choline PET/MR is a robust imaging modality for restaging biochemical recurrent PC and

  20. Value of bimodal (18)F-choline-PET/MRI and trimodal (18)F-choline-PET/MRI/TRUS for the assessment of prostate cancer recurrence after radiation therapy and radical prostatectomy.

    Science.gov (United States)

    Paparo, Francesco; Piccardo, Arnoldo; Bacigalupo, Lorenzo; Romagnoli, Andrea; Piccazzo, Riccardo; Monticone, Michela; Cevasco, Luca; Campodonico, Fabio; Conzi, Giuseppe Maria; Carmignani, Giorgio; Rollandi, Gian Andrea

    2015-08-01

    Between 27% and 53% of all patients who undergo radical prostatectomy (RP) or radiation therapy (RT) as the first-line treatment of prostate cancer (PCa) develop a biochemical recurrence. Imaging plays a pivotal role in restaging by helping to distinguish between local relapse and metastatic disease (i.e., lymph-node and skeletal metastases). At present, the most promising tools for assessing PCa patients with biochemical recurrence are multiparametric magnetic resonance imaging (mpMRI) and positron emission tomography (PET)/computed tomography (CT) with radio-labeled choline derivatives. The main advantage of mpMRI is its high diagnostic accuracy in detecting local recurrence, while choline-PET/CT is able to identify lymph-node metastases when they are not suspicious on morphological imaging. The most recent advances in the field of fusion imaging have shown that multimodal co-registration, synchronized navigation, and combined interpretation are more valuable than the individual; separate assessment offered by different diagnostic techniques. The objective of the present essay was to describe the value of bimodal choline-PET/mpMRI fusion imaging and trimodal choline-PET/mpMRI/transrectal ultrasound (TRUS) in the assessment of PCa recurrence after RP and RT. Bimodal choline-PET/mpMRI fusion imaging allows morphological, functional, and metabolic information to be combined, thereby overcoming the limitations of each separate imaging modality. In addition, trimodal real-time choline-PET/mpMRI/TRUS fusion imaging may be useful for the planning and real-time guidance of biopsy procedures in order to obtain histological confirmation of the local recurrence.

  1. Studies of antimony telluride and copper telluride films electrodeposition from choline chloride containing ionic liquids

    Energy Technology Data Exchange (ETDEWEB)

    Catrangiu, Adriana-Simona; Sin, Ion [Department of Inorganic Chemistry, Physical Chemistry and Electrochemistry, POLITEHNICA University of Bucharest, Calea Grivitei 132, Bucharest (Romania); Prioteasa, Paula [INCDIE ICPE-Advanced Research, Splaiul Unirii 313, Bucharest (Romania); Cotarta, Adina [Department of Inorganic Chemistry, Physical Chemistry and Electrochemistry, POLITEHNICA University of Bucharest, Calea Grivitei 132, Bucharest (Romania); Cojocaru, Anca, E-mail: a_cojocaru@chim.upb.ro [Department of Inorganic Chemistry, Physical Chemistry and Electrochemistry, POLITEHNICA University of Bucharest, Calea Grivitei 132, Bucharest (Romania); Anicai, Liana [Center of Surface Science and Nanotechnology, University POLITEHNICA of Bucharest, Splaiul Independentei 313, Bucharest (Romania); Visan, Teodor [Department of Inorganic Chemistry, Physical Chemistry and Electrochemistry, POLITEHNICA University of Bucharest, Calea Grivitei 132, Bucharest (Romania)

    2016-07-29

    Cyclic voltammetry and electrochemical impedance spectroscopy were used to investigate the deposition of antimony telluride or copper telluride from ionic liquid consisting in mixture of choline chloride with oxalic acid. In addition, the cathodic process during copper telluride formation was studied in the mixture of choline chloride with ethylene glycol. The results indicate that the Pt electrode is first covered with a Te layer, and then the more negative polarisation leads to the deposition of Sb{sub x}Te{sub y} or Cu{sub x}Te{sub y} semiconductor compounds. Thin films were deposited on copper and carbon steel at 60–70 °C and were characterised by scanning electron microscopy, energy X-ray dispersive spectroscopy (EDS), and X-ray diffraction (XRD). Their stoichiometry depends on the bath composition and applied potential. EDS and XRD patterns indicate the possible synthesis of stoichiometric Sb{sub 2}Te{sub 3} phase and Cu{sub 2}Te, Cu{sub 5}Te{sub 3}, and Cu{sub 2.8}Te{sub 2} phases, respectively, by controlling the ratio of ion concentrations in ionic liquid electrolytes and deposition potential. - Highlights: • Sb{sub x}Te{sub y} and Cu{sub x}Te{sub y} films electrodeposited from choline-chloride-based ionic liquids. • The stoichiometry of film depends on the bath composition and deposition potential. • Sb{sub 2}Te{sub 3}, Cu{sub 2}Te, Cu{sub 5}Te{sub 3}, Cu{sub 2.8}Te{sub 2} phases were identified in X-ray diffraction patterns.

  2. Effects of betaine supplementation and choline deficiency on folate deficiency-induced hyperhomocysteinemia in rats.

    Science.gov (United States)

    Liu, Ying; Liu, Yi-qun; Morita, Tatsuya; Sugiyama, Kimio

    2012-01-01

    The effect of betaine status on folate deficiency-induced hyperhomocysteinemia was investigated to determine whether folate deficiency impairs homocysteine removal not only by the methionine synthase (MS) pathway but also by the betaine-homocysteine S-methyltransferase (BHMT) pathway. For this purpose, we investigated the effect of dietary supplementation with betaine at a high level (1%) in rats fed a folate-deprived 10% casein diet (10C) and 20% casein diet (20C). We also investigated the effect of choline deprivation on folate deficiency-induced hyperhomocysteinemia in rats fed 20C. Supplementation of folate-deprived 10C and 20C with 1% betaine significantly suppressed folate deprivation-induced hyperhomocysteinemia, but the extent of suppression was partial or limited, especially in rats fed 10C, the suppression of plasma homocysteine increment being 48.5% in rats fed 10C and 69.7% in rats fed 20C. Although betaine supplementation greatly increased hepatic betaine concentration and BHMT activity, these increases did not fully explain why the effect of betaine supplementation was partial or limited. Folate deprivation markedly increased the hepatic concentration of N,N-dimethylglycine (DMG), a known inhibitor of BHMT, and there was a significant positive correlation between hepatic DMG concentration and plasma homocysteine concentration, suggesting that folate deficiency increases hepatic DMG concentration and thereby depresses BHMT reaction, leading to interference with the effect of betaine supplementation. Choline deprivation did not increase plasma homocysteine concentration in rats fed 20C, but it markedly enhanced plasma homocysteine concentration when rats were fed folate-deprived 20C. This indicates that choline deprivation reinforced folate deprivation-induced hyperhomocysteinemia. Increased hepatic DMG concentration was also associated with such an effect. These results support the concept that folate deficiency impairs homocysteine metabolism not only

  3. Choline and methionine differentially alter methyl carbon metabolism in bovine neonatal hepatocytes.

    Science.gov (United States)

    Chandler, Tawny L; White, Heather M

    2017-01-01

    Intersections in hepatic methyl group metabolism pathways highlights potential competition or compensation of methyl donors. The objective of this experiment was to examine the expression of genes related to methyl group transfer and lipid metabolism in response to increasing concentrations of choline chloride (CC) and DL-methionine (DLM) in primary neonatal hepatocytes that were or were not exposed to fatty acids (FA). Primary hepatocytes isolated from 4 neonatal Holstein calves were maintained as monolayer cultures for 24 h before treatment with CC (61, 128, 2028, and 4528 μmol/L) and DLM (16, 30, 100, 300 μmol/L), with or without a 1 mmol/L FA cocktail in a factorial arrangement. After 24 h of treatment, media was collected for quantification of reactive oxygen species (ROS) and very low-density lipoprotein (VLDL), and cell lysates were collected for quantification of gene expression. No interactions were detected between CC, DLM, or FA. Both CC and DLM decreased the expression of methionine adenosyltransferase 1A (MAT1A). Increasing CC did not alter betaine-homocysteine S-methyltranferase (BHMT) but did increase 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) and methylenetetrahydrofolate reductase (MTHFR) expression. Increasing DLM decreased expression of BHMT and MTR, but did not affect MTHFR. Expression of both phosphatidylethanolamine N-methyltransferase (PEMT) and microsomal triglyceride transfer protein (MTTP) were decreased by increasing CC and DLM, while carnitine palmitoyltransferase 1A (CPT1A) was unaffected by either. Treatment with FA decreased the expression of MAT1A, MTR, MTHFR and tended to decrease PEMT but did not affect BHMT and MTTP. Treatment with FA increased CPT1A expression. Increasing CC increased secretion of VLDL and decreased the accumulation of ROS in media. Within neonatal bovine hepatocytes, choline and methionine differentially regulate methyl carbon pathways and suggest that choline may play a critical role in

  4. Opioid receptor subtypes mediating the noise-induced decreases in high-affinity choline uptake in the rat brain.

    Science.gov (United States)

    Lai, H; Carino, M A

    1992-07-01

    Acute (20 min) exposure to 100-dB white noise elicits a naltrexone-sensitive decrease in sodium-dependent high-affinity choline uptake in the frontal cortex and hippocampus of the rat. In the present study, the subtypes of opioid receptors involved were investigated by pretreating rats with microinjection of specific opioid-receptor antagonists into the lateral cerebroventricle before noise exposure. We found that the noise-induced decrease in high-affinity choline uptake in the hippocampus was blocked by pretreatment with either mu-, delta-, or kappa-opioid-receptor antagonists, whereas the effect of noise on frontal cortical high-affinity choline uptake was blocked by a mu- and delta- but not by a kappa-antagonist. These data further confirm the role of endogenous opioids in mediating the effects of noise on central cholinergic activity and indicate that different neural mechanisms are involved in the effects of noise on the frontal cortical and hippocampal cholinergic systems.

  5. An Incidental Renal Oncocytoma: 18F-Choline PET/MRI

    Directory of Open Access Journals (Sweden)

    Andrew Mallia

    2016-04-01

    Full Text Available PET/MRI is a new hybrid imaging modality and has the potential to become a powerful imaging tool. It is currently one of the most active areas of research in diagnostic imaging. The characterisation of an incidental renal lesion can be difficult. In particular, the differentiation of an oncocytoma from other solid renal lesions such as renal cell carcinoma (RCC represents a diagnostic challenge. We describe the detection of an incidental renal oncocytoma in a 79-year gentleman who underwent a re-staging 18F-Choline PET/MRI following a rise in PSA values (4.07, nadir 1.3.

  6. Therapy assessment in prostate cancer using choline and PSMA PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Ceci, Francesco; Castellucci, Paolo; Fanti, Stefano [University of Bologna, Nuclear Medicine Unit, S. Orsola-Malpighi University Hospital, Bologna (Italy); Herrmann, Ken [University Hospital Essen, Department of Nuclear Medicine, Essen (Germany); University of California Los Angeles, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, Los Angeles, CA (United States); Hadaschik, Boris [University Hospital Essen, Department of Urology, Essen (Germany)

    2017-08-15

    While PET with non-FDG tracers (mainly choline and Ga-PSMA) has commonly been used for restaging in men with biochemically recurrent prostate cancer, as well as for primary staging, it is only recently that a few preliminary studies have addressed the possible use of PET for monitoring the response to systemic therapy of metastatic disease, especially innovative treatments such as abiraterone and enzalutamide. This article aims to evaluate the role of PET imaging with different non-FDG radiotracers for assessment of therapy in advanced prostate cancer patients. (orig.)

  7. Prostate cancer: a comparative study of {sup 11}C-choline PET and MR imaging combined with proton MR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, Takako; Lee, Jin; Takahashi, Nobukazu; Oka, Takashi; Shizukuishi, Kazuya; Inoue, Tomio [Yokohama City University School of Medicine, Department of Radiology, Yokohama (Japan); Uemura, Hiroji; Kubota, Yoshinobu [Yokohama City University School of Medicine, Department of Urology, Kanagawa (Japan); Sasaki, Takeshi [Yokohama City University School of Medicine, Department of Pathology, Kanagawa (Japan); Endou, Hisashi [Yokohama City University School of Medicine, Department of Pharmacy, Kanagawa (Japan)

    2005-07-01

    Prostate cancer is difficult to visualise in its early stages using current imaging technology. The present study aimed to clarify the utility of {sup 11}C-choline PET for localising and evaluating cancer lesions in patients with prostate cancer by conducting a prospective comparison with magnetic resonance (MR) imaging combined with proton MR spectroscopy. PET and MR imaging combined with proton MR spectroscopy were performed in 20 patients with prostate cancer. Correlations among the metabolite ratio of choline + creatine to citrate (Cho+Cr/Ci) on MR spectroscopy, serum PSA and maximum standardised uptake value (SUV{sub max}) of {sup 11}C-choline were assessed. The location of the primary lesion was assessed by the site of SUV{sub max} and the laterality of the highest Cho+Cr/Ci ratio and confirmed by examination of surgical pathology specimens (n=16). PET exhibited a diagnostic sensitivity of 100% (20/20) for primary lesions, while the sensitivities of MR imaging and MR spectroscopy were 60% (12/20) and 65% (13/20), respectively. Weak linear correlations were observed between SUV{sub max} and serum PSA (r=0.52, p<0.05), and between SUV{sub max} and Cho+Cr/Ci ratio (r=0.49, p<0.05). Regarding the localisation of main primary lesions, PET results agreed with pathological findings in 13 patients (81%) ({kappa}=0.59), while MR spectroscopy results were in accordance with pathological findings in eight patients (50%) ({kappa}=0.11). This preliminary study suggests that {sup 11}C-choline PET may provide more accurate information regarding the localisation of main primary prostate cancer lesions than MR imaging/MR spectroscopy. A further clinical study of {sup 11}C-choline PET in a large number of patients suspected of prostate cancer will be necessary to determine the clinical utility of {sup 11}C-choline PET in patients who clinically require biopsy. (orig.)

  8. An efficient and green method for regio- and chemo-selective Friedel–Crafts acylations using a deep eutectic mixture ([CholineCl][ZnCl2]3)

    DEFF Research Database (Denmark)

    Hoang, Tran Phuong; Nguyen, Hai Truong; Hansen, Poul Erik

    2016-01-01

    [CholineCl][ZnCl2]3, a deep eutectic solvent between choline chloride and ZnCl2, has been used as a dual function catalyst and green solvent for the Friedel–Crafts acylation of aromatic compounds instead of using the moisture-sensitive Lewis acids and volatile organic solvents. The reactions...... are performed with high yields under microwave irradiation with short reaction times for the synthesis of ketones. Interestingly, indole derivatives are regioselectively acylated in the 3-position under mild conditions with high yields without NH protection. Three new ketone products are synthesized. [Choline......Cl][ZnCl2]3 is easily synthesized from choline chloride and zinc chloride at a low cost, with easy purification and environmentally benign compounds. [CholineCl][ZnCl2]3 can be reused up to five times without loss of catalytic activity, making it ideal in industrial processes....

  9. The detection rate of [11C]Choline-PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer

    International Nuclear Information System (INIS)

    Krause, B.J.; Souvatzoglou, M.; Tuncel, M.; Herrmann, K.; Buck, A.K.; Praus, C.; Schwaiger, M.; Schuster, T.; Geinitz, H.; Treiber, U.

    2008-01-01

    An increase of the serum PSA-level is a sensitive in vitro marker for recurrent prostate cancer. However, it remains difficult to differentiate between local, regional or distant recurrent disease. The aim of this study was to assess the relationship between the detection rate of [ 11 C]Choline-PET/CT and the serum PSA-level in patients with a biochemical recurrence of prostate cancer with the view towards localisation of recurrent disease. Sixty-three patients (mean age, 68.8 ± 6.9; range, 45-83 years) with biochemical recurrence after primary therapy for prostate cancer were included in the analysis. Mean PSA-levels were 5.9 ± 9.7 ng/ml (range, 0.2-39 ng/ml; median, 2.15). Of the 63 patients, 17 were under anti-androgen therapy at the time of [ 11 C]Choline PET/CT. Patients underwent a [ 11 C]Choline-PET/CT study after injection of 656 ± 119 MBq [ 11 C]Choline on a Sensation 16 Biograph PET/CT scanner. Of the 63 patients, 35 (56%) showed a pathological [ 11 C]Choline uptake. The detection rate of [ 11 C]Choline-PET/CT showed a relationship with the serum PSA-level: The detection rate was 36% for a PSA-value 11 C]Choline-PET/CT (p = 0.374). As an important result our study shows that even for PSA-values 11 C]Choline-PET/CT is 36%. Furthermore, the detection rate of [ 11 C]Choline-PET/CT shows a positive relationship with serum PSA-levels in patients with biochemical recurrence of prostate cancer after primary therapy. Therefore, in these patients, [ 11 C]Choline PET/CT allows not only to diagnose but also to localise recurrent disease with implications on disease management (localised vs systemic therapy). (orig.)

  10. Effect of choline on antioxidant defenses and gene expressions of Nrf2 signaling molecule in the spleen and head kidney of juvenile Jian carp (Cyprinus carpio var. Jian).

    Science.gov (United States)

    Wu, Pei; Jiang, Wei-Dan; Liu, Yang; Chen, Gang-Fu; Jiang, Jun; Li, Shu-Hong; Feng, Lin; Zhou, Xiao-Qiu

    2014-06-01

    The present work evaluates the effects of various levels of dietary choline on antioxidant defenses and gene expressions of Nrf2 signaling molecule in spleen and head kidney of juvenile Jian carp (Cyprinus carpio var. Jian). Fish were fed with six different experimental diets containing graded levels of choline at 165 (choline-deficient control), 310, 607, 896, 1167 and 1820 mg kg(-1) diet for 65 days. At the end of the feeding trail, fish were challenged with Aeromonas hydrophila and mortalities were recorded over 17 days. Dietary choline significantly decreased malondialdehyde and protein carbonyl contents in spleen and head kidney. However, anti-superoxide anion and anti-hydroxyl radical activities in spleen and head kidney also decreased. Interestingly, activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) in spleen, GPx activity in head kidney, and glutathione contents in spleen and head kidney were decreased with increase of dietary choline levels up to a certain point, whereas, activities of SOD, GST and GR in head kidney showed no significantly differences among groups. Similarly, expression levels of CuZnSOD, MnSOD, CAT, GPx1a, GPx1b and GR gene in spleen and head kidney were significantly lower in group with choline level of 607 mg kg(-1) diet than those in the choline-deficient group. The relative gene expressions of Nrf2 in head kidney and Keap1a in spleen and head kidney were decreased with increasing of dietary choline up to a certain point. However, the relative gene expression of Nrf2 in spleen were not significantly affected by dietary choline. In conclusion, dietary choline decreased the oxidant damage and regulated the antioxidant system in immune organs of juvenile Jian carp. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Overexpression, purification and crystallization of a choline-binding protein CbpI from Streptococcus pneumoniae

    International Nuclear Information System (INIS)

    Paterson, Neil G.; Riboldi-Tunicliffe, Alan; Mitchell, Timothy J.; Isaacs, Neil W.

    2006-01-01

    The choline-binding protein CbpI from S. pneumoniae has been purified and crystallized and diffraction data have been collected to 3.5 Å resolution. The choline-binding protein CbpI from Streptococcus pneumoniae is a 23.4 kDa protein with no known function. The protein has been successfully purified initially using Ni–NTA chromatography and to homogeneity using Q-Sepharose ion-exchange resin as an affinity column. CbpI was crystallized using PEG 3350 as a precipitant and X-ray crystallographic analysis showed that the crystals belonged to the tetragonal space group P4, with unit-cell parameters a = b = 83.31, c = 80.29 Å, α = β = γ = 90°. The crystal contains two molecules in the asymmetric unit with a solvent content of 55.7% (V M = 2.77 Å 3 Da −1 ) and shows a diffraction limit of 3.5 Å

  12. Dietary choline supplementation in adult rats improves performance on a test of recognition memory.

    Science.gov (United States)

    Moreno, Hayarelis; Hall, Geoffrey; Gallo, Milagros; de Brugada, Isabel

    2018-04-22

    In two experiments adult rats (aged at least 6 months at the start of the procedure) received a diet enriched with added choline for a period of 10 weeks; control subjects were maintained on a standard diet during this time. All rats then underwent the spontaneous object recognition (SOR) procedure in which they were exposed to a pair of objects and then tested, after a retention interval, to a display with one object changed. Exploration of the changed object indicates retention and use of information acquired during the exposure phase. All subjects showed retention with a 24-h interval (Experiments 1 and 2) and when retested after a further 24 h (Experiment 1). But when tested for the first time after a 48-h interval (Experiment 2), control subjects showed no evidence of retention, exploring both objects equally, whereas those given the dietary supplement continued to show a preference for the changed object. This supports the conclusion that dietary choline supplementation can enhance performance on a task regarded as a test of declarative memory, and will do so even when the supplementations is given in adulthood. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Electrochemical synthesis of nanosized TiO2 nanopowder involving choline chloride based ionic liquids

    International Nuclear Information System (INIS)

    Anicai, Liana; Petica, Aurora; Patroi, Delia; Marinescu, Virgil; Prioteasa, Paula; Costovici, Stefania

    2015-01-01

    Highlights: • TiO 2 nanopowder electrochemically prepared using choline chloride based ionic liquids. • The new proposed method allowed high anodic synthesis efficiencies of minimum 92%. • High surface area of the electrochemically synthesized titania nanopowders. • Enhanced photocatalytic activity. - Abstract: The paper presents some experimental results regarding the electrochemical synthesis of TiO 2 nanopowders through anodic dissolution of Ti metal in choline chloride based eutectic mixtures (DES). A detailed characterization of the obtained titania has been performed, using various techniques, including XRD, Raman spectroscopy, XPS, SEM associated with EDX analysis, BET and UV–vis diffuse reflectance spectra. The anodic behavior of Ti electrode in DES has been also investigated. The photoreactivity of the synthesized materials was evaluated for the degradation of Orange II dye under UV (λ = 365 nm) and visible light irradiation. An anodic synthesis efficiency of minimum 92% has been determined. The as-synthesized TiO 2 showed amorphous structure and a calcination post-treatment at temperatures between 400 and 600 °C yielded anatase. The anodically obtained nanocrystalline oxides have crystallite sizes of 8–18 nm, a high surface area and enhanced photocatalytic effect

  14. Spectrophotometric determination of Sc in eriochrome cyanine R(chrome azurol S) - phosphatidyl choline system

    International Nuclear Information System (INIS)

    Xu, Y.; Chen, X.; Hu, Z.

    1987-01-01

    Eriochrome cyanine R(chrome azurol S) is used as a color reagent to determine Sc in the presence of phosphatidyl choline, eta = 3.7 * 10 4 (4.5 * 10 4 ). This method has been connected to extraction separation to determine Sc in the presence of rare earth elements, and good results have been obtained. Phosphatidyl choline(PC) is a biochemical reagent, which can be used as a surfactant. It has been reported that chrome azurol S(CAS) can be used to determine Be in the presence of PC but it has not been reported that eriochrome cyanine R(ECR) and CAS can been used to determine Sc in the presence of PC. This paper has put forward a method by which Sc can be determined. ECR (CAS) has been used as a color reagent and PC as a surfactant. Conditional experiments have been made and this method has been connected to extraction separation. Tributyl phosphate (TBP) extracts Sc from rare earth elements to make a determination and good results have been obtained

  15. Immunolocalization of choline acetyltransferase of common type in the central brain mass of Octopus vulgaris

    Directory of Open Access Journals (Sweden)

    A. Casini

    2012-07-01

    Full Text Available Acetylcholine, the first neurotransmitter to be identified in the vertebrate frog, is widely distributed among the animal kingdom. The presence of a large amount of acetylcholine in the nervous system of cephalopods is well known from several biochemical and physiological studies. However, little is known about the precise distribution of cholinergic structures due to a lack of a suitable histochemical technique for detecting acetylcholine. The most reliable method to visualize the cholinergic neurons is the immunohistochemical localization of the enzyme choline acetyltransferase, the synthetic enzyme of acetylcholine. Following our previous study on the distribution patterns of cholinergic neurons in the Octopus vulgaris visual system, using a novel antibody that recognizes choline acetyltransferase of the common type (cChAT, now we extend our investigation on the octopus central brain mass. When applied on sections of octopus central ganglia, immunoreactivity for cChAT was detected in cell bodies of all central brain mass lobes with the notable exception of the subfrontal and subvertical lobes. Positive varicosed nerves fibers where observed in the neuropil of all central brain mass lobes.

  16. Immunolocalization of choline acetyltransferase of common type in the central brain mass of Octopus vulgaris.

    Science.gov (United States)

    Casini, A; Vaccaro, R; D'Este, L; Sakaue, Y; Bellier, J P; Kimura, H; Renda, T G

    2012-07-19

    Acetylcholine, the first neurotransmitter to be identified in the vertebrate frog, is widely distributed among the animal kingdom. The presence of a large amount of acetylcholine in the nervous system of cephalopods is well known from several biochemical and physiological studies. However, little is known about the precise distribution of cholinergic structures due to a lack of a suitable histochemical technique for detecting acetylcholine. The most reliable method to visualize the cholinergic neurons is the immunohistochemical localization of the enzyme choline acetyltransferase, the synthetic enzyme of acetylcholine. Following our previous study on the distribution patterns of cholinergic neurons in the Octopus vulgaris visual system, using a novel antibody that recognizes choline acetyltransferase of the common type (cChAT), now we extend our investigation on the octopus central brain mass. When applied on sections of octopus central ganglia, immunoreactivity for cChAT was detected in cell bodies of all central brain mass lobes with the notable exception of the subfrontal and subvertical lobes. Positive varicosed nerves fibers where observed in the neuropil of all central brain mass lobes.

  17. In vitro inhibition of choline acetyltransferase by a series of 2-benzylidene-3-quinuclidinones

    International Nuclear Information System (INIS)

    Capacio, B.R.

    1988-01-01

    Ten substituted 2-benzylidene-3-quinuclidinones were synthesized and evaluated for their relative potency as in vitro inhibitors of choline acetyltransferase (ChAT). Acetylcholine (ACh) synthesis was followed radiometrically by the incorporation of labeled acetate originating from 14 C-acetyl-CoA. Woolf-Augustinsson-Hofstee data analysis was used to calculate Vmax, Km, and Ki values. The inhibition was found to be noncompetitive or uncompetitive with respect to choline. Quantitative structure activity relationship correlations demonstrated a primary dependence on κ-σ, as well as steric properties of the substituted benzene ring. Additional radiometric and spectrophotometric were performed with 2-(3'-methyl)-benzylidene-3-quinuclidinone, one of the more potent analogs, to further elucidate the inhibitory mechanism. ChAT-mediated cleavage of ACh was measured spectrophotometrically by following the appearance of NADH at 340 nanometers in an enzyme coupled assay. Lineweaver-Burk analysis indicated mixed or uncompetitive inhibition with respect to both substrates of the forward reaction, suggesting interference with a rate limiting step

  18. Multilayer Choline Phosphate Molecule Modified Surface with Enhanced Cell Adhesion but Resistance to Protein Adsorption.

    Science.gov (United States)

    Chen, Xingyu; Yang, Ming; Liu, Botao; Li, Zhiqiang; Tan, Hong; Li, Jianshu

    2017-08-22

    Choline phosphate (CP), which is a new zwitterionic molecule, and has the reverse order of phosphate choline (PC) and could bind to the cell membrane though the unique CP-PC interaction. Here we modified a glass surface with multilayer CP molecules using surface-initiated atom-transfer radical polymerization (SI-ATRP) and the ring-opening method. Polymeric brushes of (dimethylamino)ethyl methacrylate (DMAEMA) were synthesized by SI-ATRP from the glass surface. Then the grafted PDMAEMA brushes were used to introduce CP groups to fabricate the multilayer CP molecule modified surface. The protein adsorption experiment and cell culture test were used to evaluate the biocompatibility of the modified surfaces by using human umbilical veinendothelial cells (HUVECs). The protein adsorption results demonstrated that the multilayer CP molecule decorated surface could prevent the adsorption of fibrinogen and serum protein. The adhesion and proliferation of cells were improved significantly on the multilayer CP molecule modified surface. Therefore, the biocompatibility of the material surface could be improved by the modified multilayer CP molecule, which exhibits great potential for biomedical applications, e.g., scaffolds in tissue engineering.

  19. Electrochemical synthesis of nanosized TiO{sub 2} nanopowder involving choline chloride based ionic liquids

    Energy Technology Data Exchange (ETDEWEB)

    Anicai, Liana, E-mail: lanicai@itcnet.ro [POLITEHNICA University of Bucharest, Center of Surface Science and Nanotechnology, Splaiul Independentei 313, Bucharest, 060042 (Romania); Petica, Aurora [Leather and Footwear Research Institute (ICPI), Ion Minulescu 93, Bucharest, 031215 (Romania); Patroi, Delia; Marinescu, Virgil; Prioteasa, Paula [INCDIE ICPE-Advanced Research, Splaiul Unirii 313, Bucharest (Romania); Costovici, Stefania [POLITEHNICA University of Bucharest, Center of Surface Science and Nanotechnology, Splaiul Independentei 313, Bucharest, 060042 (Romania)

    2015-09-15

    Highlights: • TiO{sub 2} nanopowder electrochemically prepared using choline chloride based ionic liquids. • The new proposed method allowed high anodic synthesis efficiencies of minimum 92%. • High surface area of the electrochemically synthesized titania nanopowders. • Enhanced photocatalytic activity. - Abstract: The paper presents some experimental results regarding the electrochemical synthesis of TiO{sub 2} nanopowders through anodic dissolution of Ti metal in choline chloride based eutectic mixtures (DES). A detailed characterization of the obtained titania has been performed, using various techniques, including XRD, Raman spectroscopy, XPS, SEM associated with EDX analysis, BET and UV–vis diffuse reflectance spectra. The anodic behavior of Ti electrode in DES has been also investigated. The photoreactivity of the synthesized materials was evaluated for the degradation of Orange II dye under UV (λ = 365 nm) and visible light irradiation. An anodic synthesis efficiency of minimum 92% has been determined. The as-synthesized TiO{sub 2} showed amorphous structure and a calcination post-treatment at temperatures between 400 and 600 °C yielded anatase. The anodically obtained nanocrystalline oxides have crystallite sizes of 8–18 nm, a high surface area and enhanced photocatalytic effect.

  20. Overexpression, purification and crystallization of a choline-binding protein CbpI from Streptococcus pneumoniae

    Energy Technology Data Exchange (ETDEWEB)

    Paterson, Neil G., E-mail: neison@chem.gla.ac.uk; Riboldi-Tunicliffe, Alan [Department of Chemistry and WestCHEM, Glasgow Biomedical Research Centre (GBRC), University of Glasgow, 120 University Place, Glasgow G12 8TA,Scotland (United Kingdom); Mitchell, Timothy J. [Division of Infection and Immunity (IBLS), Glasgow Biomedical Research Centre (GBRC), University of Glasgow, 120 University Place, Glasgow G12 8TA,Scotland (United Kingdom); Isaacs, Neil W. [Department of Chemistry and WestCHEM, Glasgow Biomedical Research Centre (GBRC), University of Glasgow, 120 University Place, Glasgow G12 8TA,Scotland (United Kingdom)

    2006-07-01

    The choline-binding protein CbpI from S. pneumoniae has been purified and crystallized and diffraction data have been collected to 3.5 Å resolution. The choline-binding protein CbpI from Streptococcus pneumoniae is a 23.4 kDa protein with no known function. The protein has been successfully purified initially using Ni–NTA chromatography and to homogeneity using Q-Sepharose ion-exchange resin as an affinity column. CbpI was crystallized using PEG 3350 as a precipitant and X-ray crystallographic analysis showed that the crystals belonged to the tetragonal space group P4, with unit-cell parameters a = b = 83.31, c = 80.29 Å, α = β = γ = 90°. The crystal contains two molecules in the asymmetric unit with a solvent content of 55.7% (V{sub M} = 2.77 Å{sup 3} Da{sup −1}) and shows a diffraction limit of 3.5 Å.

  1. Synthesis and preclinical evaluation of the choline transport tracer deshydroxy-[18F]fluorocholine ([18F]dOC)

    International Nuclear Information System (INIS)

    Henriksen, G.; Herz, M.; Hauser, A.; Schwaiger, M.; Wester, H.-J.

    2004-01-01

    11 C-labeled choline ([ 11 C]CHO) and 18 F-fluorinated choline analogues have been demonstrated to be valuable tracers for in vivo imaging of neoplasms by means of positron emission tomography (PET). The objective of the present study was to evaluate whether deshydroxy-[ 18 F]fluorocholine, ([ 18 F]dOC), a non-metabolizable [ 18 F]fluorinated choline analogue, can serve as a surrogate for cholines that are able to be phosphorylated and thus allow PET-imaging solely by addressing the choline transport system. The specificity of uptake of [ 18 F]dOC was compared with that of [ 11 C]choline ([ 11 C]CHO) in cultured rat pancreatic carcinoma and PC-3 human prostate cancer cells in vitro. In addition, biodistribution of [ 18 F]dOC and [ 11 C]CHO was compared in AR42J- and PC-3 tumor bearing mice. The in vitro studies revealed that membrane transport of both compounds can be inhibited in a concentration dependent manner by similar concentrations of cold choline (IC 50 [ 18 F]dOC= 11 μM; IC 50 [ 11 C]CHO=13 μM. In vitro studies with PC-3 and AR42J cells revealed that the internalized fraction of [ 18 F]dOC after 5 min incubation time is comparable to that of [ 11 C]CHO, whereas the uptake of [ 11 C]CHO was superior after 20 min incubation time. As for [ 11 C]CHO, kidney and liver were also the primary sites of uptake for [ 18 F]dOC in vivo. Biodistribution data after simultaneous injection of both tracers into AR42J tumor bearing mice revealed slightly higher tumor uptake for [ 18 F]dOC at 10 min post-injection, whereas [ 11 C]CHO uptake was higher at later time points. In conclusion, [ 18 F]dOC is taken up into AR42J rat pancreatic carcinoma and PC-3 human prostate cancer cells by a choline specific transport system. Similar transport rates of [ 18 F]dOC and [ 11 C]CHO result in comparable cellular uptake levels at early time points. In contrast to [ 18 F]dOC, which is transported but not intracellularily trapped, the choline kinase substrate [ 11 C]CHO is transported

  2. SALT ACCLIMATION OF TRITICUM-AESTIVUM BY CHOLINE CHLORIDE - PLANT-GROWTH, MINERAL-CONTENT, AND CELL-PERMEABILITY

    NARCIS (Netherlands)

    MANSOUR, MM; STADELMANN, EJ; LEESTADELMANN, OY

    1993-01-01

    Seedlings of a salt sensitive line of Triticum aestivum were grown in Hoagland solution supplemented with 100 mM NaCl following a pretreatment with choline chloride (ChCl). Changes in growth, mineral content of roots and shoots, and passive permeability of the cell membrane were measured. Relative

  3. Effect of rumen-protected choline on performance, blood metabolites, and hepatic triacylglycerols of periparturient dairy cattle

    NARCIS (Netherlands)

    Zom, R.L.G.; Baal, van J.; Goselink, R.M.A.; Bakker, J.A.; Veth, M.J.; Vuuren, van A.M.

    2011-01-01

    The effects of a dietary supplement of rumen-protected choline on feed intake, milk yield, milk composition, blood metabolites, and hepatic triacylglycerol were evaluated in periparturient dairy cows. Thirty-eight multiparous cows were blocked into 19 pairs and then randomly allocated to either one

  4. Protein τ-mediated effects on rat hippocampal choline transporters CHT1 and τ-amyloid β interactions

    Czech Academy of Sciences Publication Activity Database

    Krištofíková, Z.; Řípová, D.; Hegnerová, Kateřina; Šírová, J.; Homola, Jiří

    2013-01-01

    Roč. 38, č. 9 (2013), s. 1949-1959 ISSN 0364-3190 Institutional support: RVO:67985882 Keywords : Tau protein * Amyloid β peptide * Choline transporter Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 2.551, year: 2013

  5. Comparison of C-11-choline and F-18-FDG PET in primary diagnosis and staging of patients with thoracic cancer

    NARCIS (Netherlands)

    Pieterman, RM; Que, TH; Elsinga, PH; Pruim, J; van Putten, JWG; Willemsen, ATM; Vaalburg, W; Groen, HJM

    PET with F-18-FDG is used for detection and staging of thoracic cancer; however, more specific PET radiopharmaceuticals would be welcome. C-11-labeled choline (CHOL) is a new radiopharmaceutical potentially useful for tumor imaging, since it is incorporated into cell membranes as

  6. Suppression Effects of Betaine-Enriched Spinach on Hyperhomocysteinemia Induced by Guanidinoacetic Acid and Choline Deficiency in Rats

    Directory of Open Access Journals (Sweden)

    Yi-Qun Liu

    2014-01-01

    Full Text Available Betaine is an important natural component of rich food sources, especially spinach. Rats were fed diets with betaine or spinach powder at the same level of betaine for 10 days to investigate the dose-dependent effects of spinach powder supplementation on hyperhomocysteinemia induced by guanidinoacetic acid (GAA addition and choline deprivation. The GAA-induced hyperhomocysteinemia in rats fed 25% casein diet (25C was significantly suppressed by supplementation with betaine or spinach, and it was completely suppressed by taking 11.0% spinach supplementation. The choline deprivation-induced enhancement of plasma homocysteine concentration in rats fed 25% soybean protein diet (25S was markedly suppressed by 3.82% spinach. Supplementation with betaine or spinach partially prevented the effects of GAA on hepatic concentrations of methionine metabolites. The decrease in activity of betaine-homocysteine S-methyltransferase (BHMT and cystathionine β-synthase (CBS in GAA-induced hyperhomocysteinemia was recovered by supplementation with betaine or spinach. Supplementation with betaine or spinach did not affect BHMT activity, whereas it partially restored CBS activity in choline-deprived 25S. The results indicated that betaine or spinach could completely suppress the hyperhomocysteinemia induced by choline deficiency resulting from stimulating the homocysteine removal by both remethylation and cystathionine formation.

  7. Effect of rumen-protected choline supplementation on liver and adipose gene expression during the transition period in dairy cattle

    NARCIS (Netherlands)

    Goselink, R.M.A.; Baal, van J.; Widjaja, H.C.A.; Dekker, R.A.; Zom, R.L.G.; Veth, M.J.; Vuuren, van A.M.

    2013-01-01

    We previously reported that supplementation of rumen-protected choline (RPC) reduces the hepatic triacylglycerol concentration in periparturient dairy cows during early lactation. Here, we investigated the effect of RPC on the transcript levels of lipid metabolism-related genes in liver and adipose

  8. No up-regulation of the phosphatidylethanolamine N-methyltransferase pathway and choline production by sex hormones in cats

    NARCIS (Netherlands)

    Valtolina, Chiara; Vaandrager, Arie B; Favier, Robert P; Robben, Joris H; Tuohetahuntila, Maidina; Kummeling, Anne; Jeusette, Isabelle; Rothuizen, Jan

    2015-01-01

    BACKGROUND: Feline hepatic lipidosis (FHL) is a common cholestatic disease affecting cats of any breed, age and sex. Both choline deficiency and low hepatic phosphatidylethanolamine N-methyltransferase (PEMT) activity are associated with hepatic lipidosis (HL) in humans, mice and rats. The PEMT

  9. Crotoxin, the major toxin from the rattlesnake Crotalus durissus terrificus, inhibits ³H-choline uptake in guinea pig ileum

    Directory of Open Access Journals (Sweden)

    L.S. Kattah

    2000-09-01

    Full Text Available We examined the effect of crotoxin, the neurotoxic complex from the venom of the South American rattlesnake Crotalus durissus terrificus, on the uptake of ³H-choline in minces of smooth muscle myenteric plexus from guinea pig ileum. In the concentration range used (0.03-1 µM and up to 10 min of treatment, crotoxin decreased ³H-choline uptake by 50-75% compared to control. This inhibition was time dependent and did not seem to be associated with the disruption of the neuronal membrane, because at least for the first 20 min of tissue exposure to the toxin (up to 1 µM the levels of lactate dehydrogenase (LDH released into the supernatant were similar to those of controls. Higher concentrations of crotoxin or more extensive incubation times with this toxin resulted in elevation of LDH activity detected in the assay supernatant. The inhibitory effect of crotoxin on ³H-choline uptake seems to be associated with its phospholipase activity since the equimolar substitution of Sr2+ for Ca2+ in the incubation medium or the modification of the toxin with p-bromophenacyl bromide substantially decreased this effect. Our results show that crotoxin inhibits ³H-choline uptake with high affinity (EC25 = 10 ± 5 nM. We suggest that this inhibition could explain, at least in part, the blocking effect of crotoxin on neurotransmission.

  10. (18)F-choline PET/CT pitfalls in image interpretation: an update on 300 examined patients with prostate cancer.

    Science.gov (United States)

    Calabria, Ferdinando; Chiaravalloti, Agostino; Schillaci, Orazio

    2014-02-01

    F-choline PET/CT is an important diagnostic tool in the management of patients with prostate cancer (PC). The aim of this study was to describe and discuss some abnormal sites of uptake that we observed, not due to PC recurrence. Three hundred patients were submitted to F-choline PET/CT for staging or restaging of PC. Whole-body PET/CT was acquired 40 minutes after the F-choline administration. We found abnormal uptake of the tracer, not related to PC, in 48/300 patients (16%). Most of these findings were due to inflammatory processes. Furthermore, some malignant conditions, such as a case of colon cancer, a case of bladder carcinoma, and a multiple myeloma, were diagnosed. Mild uptake was also detected in some benign diseases, such as thymoma, adrenal adenoma, and sarcoidosis. Six patients showed focal brain uptake in correspondence to a meningioma. It is necessary for nuclear physicians, during clinical practice, to consider the possibility of F-choline uptake in some benign or malignant conditions for the intrinsic pharmacologic property of the tracer. An accurate medical investigation, correlative imaging with CT and/or MRI with contrast agents, laboratory data, and above all, histologic examination are often necessary for correct diagnosis.

  11. Choline Phospholipid Metabolites of Human Vascular Endothelial Cells Altered by Cyclooxygenase Inhibition, Growth Factor Depletion, and Paracrine Factors Secreted by Cancer Cells

    Directory of Open Access Journals (Sweden)

    Noriko Mori

    2003-04-01

    Full Text Available Magnetic resonance studies have previously shown that solid tumors and cancer cells in culture typically exhibit high phosphocholine and total choline. Treatment of cancer cells with the anti-inflammatory agent, indomethacin (INDO, reverted the phenotype of choline phospholipid metabolites in cancer cells towards a less malignant phenotype. Since endothelial cells form a key component of tumor vasculature, in this study, we used MR spectroscopy to characterize the phenotype of choline phospholipid metabolites in human umbilical vein endothelial cells (HUVECs. We determined the effect of growth factors, the anti-inflammatory agent INDO, and conditioned media obtained from a malignant cell line, on choline phospholipid metabolites. Growth factor depletion or treatment with INDO induced similar changes in the choline phospholipid metabolites of HUVECs. Treatment with conditioned medium obtained from MDA-MB-231 cancer cells induced changes similar to the presence of growth factor supplements. These results suggest that cancer cells secrete growth factors and/or other molecules that influence the choline phospholipid metabolism of HUVECs. The ability of INDO to alter choline phospholipid metabolism in the presence of growth factor supplements suggests that the inflammatory response pathways of HUVECs may play a role in cancer cell-HUVEC interaction and in the response of HUVECs to growth factors.

  12. Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet.

    Science.gov (United States)

    Schugar, Rebecca C; Huang, Xiaojing; Moll, Ashley R; Brunt, Elizabeth M; Crawford, Peter A

    2013-01-01

    Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666) that is very high in fat (~94% kcal), very low in carbohydrate (~1% kcal), low in protein (~5% kcal), and choline restricted (~300 mg/kg) provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal) and choline contents (300 mg/kg vs. 5 g/kg). C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet - weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction - were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.

  13. Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet.

    Directory of Open Access Journals (Sweden)

    Rebecca C Schugar

    Full Text Available Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666 that is very high in fat (~94% kcal, very low in carbohydrate (~1% kcal, low in protein (~5% kcal, and choline restricted (~300 mg/kg provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal and choline contents (300 mg/kg vs. 5 g/kg. C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet - weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction - were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.

  14. Long-term improvements in sensory inhibition with gestational choline supplementation linked to α7 nicotinic receptors through studies in Chrna7 null mutation mice.

    Science.gov (United States)

    Stevens, Karen E; Choo, Kevin S; Stitzel, Jerry A; Marks, Michael J; Adams, Catherine E

    2014-03-13

    Perinatal choline supplementation has produced several benefits in rodent models, from improved learning and memory to protection from the behavioral effects of fetal alcohol exposure. We have shown that supplemented choline through gestation and lactation produces long-term improvement in deficient sensory inhibition in DBA/2 mice which models a similar deficit in schizophrenia patients. The present study extends that research by feeding normal or supplemented choline diets to DBA/2 mice carrying the null mutation for the α7 nicotinic receptor gene (Chrna7). DBA/2 mice heterozygotic for Chrna7 were bred together. Dams were placed on supplemented (5 gm/kg diet) or normal (1.1 gm/kg diet) choline at mating and remained on the specific diet until offspring weaning. Thereafter, offspring were fed standard rodent chow. Adult offspring were assessed for sensory inhibition. Brains were obtained to ascertain hippocampal α7 nicotinic receptor levels. Choline-supplemented mice heterozygotic or null-mutant for Chrna7 failed to show improvement in sensory inhibition. Only wildtype choline-supplemented mice showed improvement with the effect solely through a decrease in test amplitude. This supports the hypothesis that gestational-choline supplementation is acting through the α7 nicotinic receptor to improve sensory inhibition. Although there was a significant gene-dose-related change in hippocampal α7 receptor numbers, binding studies did not reveal any choline-dose-related change in binding in any hippocampal region, the interaction being driven by a significant genotype main effect (wildtype>heterozygote>null mutant). These data parallel a human study wherein the offspring of pregnant women receiving choline supplementation during gestation, showed better sensory inhibition than offspring of women on placebo. Published by Elsevier B.V.

  15. A study of 11C-acetate production using 11C-choline commercial module

    International Nuclear Information System (INIS)

    Zhang Jinming; Tian Jiahe; Yao Shulin; Chen Yan

    2008-01-01

    Objective: 11 C-acetate is a useful PET tracer in evaluating myocardial metabolism but more interest has been focused on its application in tumor detection in recent years, especially hepatocellular carcinoma (HCC). This study was designed to evaluate the laboratory, preparation of 11 C-acetate with a modified 11 C-choline commercial module and to investigate its biodistribution in tumor (lung adenocarcinoma)-bearing mice as well as its potential as a tumor imaging agent. Methods: 11 C-acetate was synthesized with a modified 11 C choline module: Methyl magnesium bromide Grignard (0.1 ml of 1.5 mol/L) was load- ed to a Teflon loop before 11 CO 2 was recovered from the target. Cartier acetate solution (2 ml of 1 mmol/L) was pushed through the loop, SPE cartridges (mixed AG50 and IC-Ag) and then the QMA. The loop and cartridges were then rinsed with water. The product 11 C-acetate was then washed out from QMA with 0.9% NaCl solution into a collection vial containing diluted HCl. 11 C-carbonate was removed by nitrogen bubbling for 2 min. After neutralization with trisodium citrate, the injectable 11 C-acetate solution was obtained. The tumor-bearing mice were sacrificed. The percentage activity of injected dose per gram of tissue (% ID/g) for tumor and other tissues were calculated. One patient with known diagnosis of moderately differentiated HCC was injected with 11 C-acetate and imaged by PET/CT, followed by 18 F-fluorodeoxyglucose (FDG). Results: The synthesis yield of 11 C-acetate was (60.5 ± 8.7)% (decay conected, n=10); the radio-chemistry purity was > 98% and the synthesis time was 10 min from 11 CO 2 to 11 C-acetate. The radioactivity ratio for tumor/muscle was 1.76 at 30 min. A patient with known HCC showed positive 11 C-acetate accumulation in the tumor but was negative in 18 F-FDG. Conclusion: The synthesis of 11 C-acetate by modification of an 11 C-choline commercial module was feasible and it could be achieved with high yield, high radiochemical purity

  16. PET imaging of hepatocellular carcinoma with {sup 18}F-fluoroethylcholine and {sup 11}C-choline

    Energy Technology Data Exchange (ETDEWEB)

    Kolthammer, Jeffrey A.; Tenley, Nathan [Case Western Reserve University, Department of Biomedical Engineering, Cleveland, OH (United States); Corn, David J.; Wu, Chunying; Tian, Haibin; Wang, Yanming [University Hospitals Case Medical Center, Nuclear Medicine Division, Department of Radiology, Cleveland, OH (United States); Lee, Zhenghong [Case Western Reserve University, Department of Biomedical Engineering, Cleveland, OH (United States); University Hospitals Case Medical Center, Nuclear Medicine Division, Department of Radiology, Cleveland, OH (United States)

    2011-07-15

    Choline-based radiotracers have been studied for PET imaging of hepatocellular carcinoma (HCC). Using an {sup 18}F-labeled choline analog, instead of the {sup 11}C-labeled native choline, would facilitate its widespread use in the clinic. In this study, PET with {sup 18}F-fluoroethylcholine (FEC) and {sup 11}C-choline (CHOL) were compared using an animal model of HCC. The effects of fasting on the performance of choline-based tracers were also investigated. A woodchuck model of HCC was used to compare the two tracers, which were administered and imaged in sequence during the same imaging session. Dynamic PET images were generated spanning 50 min starting from tracer injection. Time-activity curves and tracer contrast were calculated in liver regions with tracer accumulation, and the contrast at a late time-point with the two tracers, and between fasted and nonfasted states, were compared. Foci of HCC with increased uptake ranged in size from 1.0 to 1.6 cm, with mean tumor-to-background contrast of 1.3 with FEC and 1.5 with CHOL at 50 min after injection. The tracers show similar patterns of uptake immediately following administration, and both activities plateaued at 10 min after injection. No significant differences in uptake dynamics or final contrast were observed between the fasted and nonfasted states. PET imaging of HCC is possible with both CHOL and FEC. Fasting was not found to affect accumulation of either tracer. These results encourage further investigation into the clinical utility of FEC for HCC imaging. (orig.)

  17. Application of 11C-choline PET/CT imaging for differentiating malignant from benign prostate lesions

    International Nuclear Information System (INIS)

    Li Xin; Wang Muwen; Liu Qingwei; Zhu Renjuan; Liu Lihui; Yuan Xianshun; Yao Shuzhan; Liu Songtao

    2006-01-01

    Objective: To investigate the potential of 11 C-choline PET/CT imaging for differentiating prostate cancer from benign prostate hyperplasia. Methods: A total of 45 patients with prostate lesions under- went 11 C-choline PET/CT imaging before transrectal needle biopsy. PET/CT imaging was performed 5 min after injection of 7.4 MBq/kg 11 C-choline in supine position over lower abdomen (3 min per bed with 2 beds), including the pelvis, and the whole body with 6 beds when necessary. After attenuation correction and iterative reconstruction, PET data were analyzed semi-quantitatively by measuring maximum standardized uptake values (SUV max ) in prostate lesions (P, target) and the muscles (M, non-target) and then P/M ratios were calculated. Also visual analysis was performed in different transverse, sagittal views and slices as well as three-dimensional images. Results: Eighteen prostate cancer and 27 benign prostate hyperplasia [and(or) chronic prostatitis] were all confirmed by pathology. The mean P/M ratio of prostate cancer was 4.02± 1.88, while in benign lesions was 1.87±1.21. The statistical differences of P/M ratios between them were significant (t=2.07, P 11 C-choline PET/CT imaging were 88.89%, 88.89% and 92.31% respectively. Conclusions: 11 C-choline PET/CT imaging is a valuable non-invasive technology in the diagnosis of pros- tate cancer. The P/M ratio can differentiate prostate cancer from benign lesions better than SUV. (authors)

  18. [11C]Choline PET/CT predicts survival in hormone-naive prostate cancer patients with biochemical failure after radical prostatectomy

    International Nuclear Information System (INIS)

    Giovacchini, Giampiero; Incerti, Elena; Mapelli, Paola; Gianolli, Luigi; Picchio, Maria; Kirienko, Margarita; Briganti, Alberto; Gandaglia, Giorgio; Montorsi, Francesco

    2015-01-01

    Over the last decade, PET/CT with radiolabelled choline has been shown to be useful for restaging patients with prostate cancer (PCa) who develop biochemical failure. The limitations of most clinical studies have been poor validation of [ 11 C]choline PET/CT-positive findings and lack of survival analysis. The aim of this study was to assess whether [ 11 C]choline PET/CT can predict survival in hormone-naive PCa patients with biochemical failure. This retrospective study included 302 hormone-naive PCa patients treated with radical prostatectomy who underwent [ 11 C]choline PET/CT from 1 December 2004 to 31 July 2007 because of biochemical failure (prostate-specific antigen, PSA, >0.2 ng/mL). Median PSA was 1.02 ng/mL. PCa-specific survival was estimated using Kaplan-Meier curves. Cox regression analysis was used to evaluate the association between clinicopathological variables and PCa-specific survival. The coefficients of the covariates included in the Cox regression analysis were used to develop a novel nomogram. Median follow-up was 7.2 years (1.4 - 18.9 years). [ 11 C]Choline PET/CT was positive in 101 of 302 patients (33 %). Median PCa-specific survival after prostatectomy was 14.9 years (95 % CI 9.7 - 20.1 years) in patients with positive [ 11 C]choline PET/CT. Median survival was not achieved in patients with negative [ 11 C]choline PET/CT. The 15-year PCa-specific survival probability was 42.4 % (95 % CI 31.7 - 53.1 %) in patients with positive [ 11 C]choline PET/CT and 95.5 % (95 % CI 93.5 - 97.5 %) in patients with negative [ 11 C]choline PET/CT. In multivariate analysis, [ 11 C]choline PET/CT (hazard ratio 6.36, 95 % CI 2.14 - 18.94, P < 0.001) and Gleason score >7 (hazard ratio 3.11, 95 % CI 1.11 - 8.66, P = 0.030) predicted PCa-specific survival. An internally validated nomogram predicted 15-year PCa-specific survival probability with an accuracy of 80 %. Positive [ 11 C]choline PET/CT after biochemical failure predicts PCa-specific survival in hormone

  19. Effects of anticonvulsants in vivo on high affinity choline uptake in vitro in mouse hippocampal synaptosomes.

    Science.gov (United States)

    Miller, J. A.; Richter, J. A.

    1985-01-01

    The effects of several anticonvulsant drugs on sodium-dependent high affinity choline uptake (HACU) in mouse hippocampal synaptosomes was investigated. HACU was measured in vitro after in vivo administration of the drug to mice. HACU was inhibited by drugs which have in common the ability to facilitate gamma-aminobutyric acid (GABA) transmission, pentobarbitone, phenobarbitone, barbitone, diazepam, chloridiazepoxide, and valproic acid. Dose-response relationships were determined for these drugs and the drugs' potencies at inhibiting HACU correlated well with their anticonvulsant potencies. Clonazepam, ethosuximide, carbamazepine, and barbituric acid had no effect on HACU in the doses used while phenytoin and trimethadione stimulated HACU. These results suggest that certain anticonvulsants may elicit a part of their anticonvulsant activity by modulating cholinergic neurones. This effect may be mediated through a GABA mechanism. PMID:3978310

  20. Effects of dietary amino acids, carbohydrates, and choline on neurotransmitter synthesis

    Science.gov (United States)

    Wurtman, Richard J.

    1988-01-01

    The ability of a meal to increase or decrease brain neurotransmitter synthesis has been studied. It is concluded that brain serotonin synthesis is directly controlled by the proportions of carbohydrate to protein in meals and snacks that increase or decrease brain tryptophan levels, thereby changing the substrate saturation of tryptophan hydroxylase and the rate of serotonin synthesis. The ability of serotoninergic neurons to have their output coupled to dietary macronutrients enables them to function as sensors of peripheral metabolism, and to subserve an important role in the control of appetite. The robust and selective responses of catecholaminergic and cholinergic neurons to supplemental tyrosine and choline suggest that these compounds may become useful as a new type of drug for treating deseases or conditions in which adequate quantities of the transmitter would otherwise be unavailable.

  1. The Semi-automatic Synthesis of 18F-fluoroethyl-choline by Domestic FDG Synthesizer

    Directory of Open Access Journals (Sweden)

    ZHOU Ming

    2016-02-01

    Full Text Available As an important complementary imaging agent for 18F-FDG, 18F-fluoroethyl-choline (18F-FECH has been demonstrated to be promising in brain and prostate cancer imaging. By using domestic PET-FDG-TI-I CPCU synthesizer, 18F-FECH was synthesized by different reagents and consumable supplies. The C18 column was added before the product collection bottle to remove K2.2.2. The 18F-FECH was synthesized by PET-FDG-IT-I synthesizer efficiently about 30 minutes by radiochemical yield of 42.0% (no decay corrected, n=5, and the radiochemical purity was still more than 99.0% after 6 hours. The results showed the domestic PET-FDG-IT-I synthesizer could semi-automatically synthesize injectable 18F-FECH in high efficiency and radiochemical purity

  2. Electrodeposition of copper composites from deep eutectic solvents based on choline chloride.

    Science.gov (United States)

    Abbott, Andrew P; El Ttaib, Khalid; Frisch, Gero; McKenzie, Katy J; Ryder, Karl S

    2009-06-07

    Here we describe for the first time the electrolytic deposition of copper and copper composites from a solution of the metal chloride salt in either urea-choline chloride, or ethylene glycol-choline chloride based eutectics. We show that the deposition kinetics and thermodynamics are quite unlike those in aqueous solution under comparable conditions and that the copper ion complexation is also different. The mechanism of copper nucleation is studied using chronoamperometry and it is shown that progressive nucleation leads to a bright nano-structured deposit. In contrast, instantaneous nucleation, at lower concentrations of copper ions, leads to a dull deposit. This work also pioneers the use of the electrochemical quartz crystal microbalance (EQCM) to monitor both current efficiency and the inclusion of inert particulates into the copper coatings. This technique allows the first in situ quantification or particulate inclusion. It was found that the composition of composite material was strongly dependent on the amount of species suspended in solution. It was also shown that the majority of material was dragged onto the surface rather than settling on to it. The distribution of the composite material was found to be even throughout the coating. This technology is important because it facilitates deposition of bright copper coatings without co-ligands such as cyanide. The incorporation of micron-sized particulates into ionic liquids has resulted, in one case, in a decrease in viscosity. This observation is both unusual and surprising; we explain this here in terms of an increase in the free volume of the liquid and local solvent perturbation.

  3. Blockage of High-Affinity Choline Transporter Increases Visceral Hypersensitivity in Rats with Chronic Stress

    Directory of Open Access Journals (Sweden)

    Chen Zhao

    2018-01-01

    Full Text Available Background. Visceral hypersensitivity is a common feature of irritable bowel syndrome. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1 is of crucial importance in choline uptake system. However, involvement of CHT1 in visceral hypersensitivity remains unknown. The research aimed to study the CHT1 expression in dorsal root ganglions (DRGs and the role of CHT1 in visceral hypersensitivity. Methods. Repetitive water avoidance stress (WAS was used to induce visceral hypersensitivity in rats. Colorectal distension (CRD was determined, and the abdominal withdrawal reflex (AWR and threshold intensity data were recorded to measure the visceral sensitivity. After intraperitoneal injection of hemicholinium-3 (HC-3, the specific inhibitor of CHT1, CRD data were also recorded. The CHT1 expression of DRGs was investigated by Western blotting, immunohistochemistry, and quantitative RT-PCR. Acetylcholine levels in the DRGs were detected by the assay kit. Results. Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats. After the administration of HC-3, the AWR score in WAS group was significantly increased at higher distension pressure while the threshold intensity was significantly reduced compared to the normal saline group. Acetylcholine concentration was significantly lower than the normal saline rats. Conclusion. Our research firstly reports that CHT1 is overexpressed in noninflammatory visceral hypersensitivity, and blockage of CHT1 can enhance the visceral hypersensitivity. CHT1 may play an inhibitory role in visceral hypersensitivity.

  4. Blockage of High-Affinity Choline Transporter Increases Visceral Hypersensitivity in Rats with Chronic Stress

    Science.gov (United States)

    2018-01-01

    Background Visceral hypersensitivity is a common feature of irritable bowel syndrome. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1) is of crucial importance in choline uptake system. However, involvement of CHT1 in visceral hypersensitivity remains unknown. The research aimed to study the CHT1 expression in dorsal root ganglions (DRGs) and the role of CHT1 in visceral hypersensitivity. Methods Repetitive water avoidance stress (WAS) was used to induce visceral hypersensitivity in rats. Colorectal distension (CRD) was determined, and the abdominal withdrawal reflex (AWR) and threshold intensity data were recorded to measure the visceral sensitivity. After intraperitoneal injection of hemicholinium-3 (HC-3), the specific inhibitor of CHT1, CRD data were also recorded. The CHT1 expression of DRGs was investigated by Western blotting, immunohistochemistry, and quantitative RT-PCR. Acetylcholine levels in the DRGs were detected by the assay kit. Results Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats. After the administration of HC-3, the AWR score in WAS group was significantly increased at higher distension pressure while the threshold intensity was significantly reduced compared to the normal saline group. Acetylcholine concentration was significantly lower than the normal saline rats. Conclusion Our research firstly reports that CHT1 is overexpressed in noninflammatory visceral hypersensitivity, and blockage of CHT1 can enhance the visceral hypersensitivity. CHT1 may play an inhibitory role in visceral hypersensitivity. PMID:29849603

  5. Enhanced incorporation of fatty acid into phosphatidyl choline that parallels histamine discharge in mast cells

    International Nuclear Information System (INIS)

    Castle, J.D.; Castle, A.M.; Ma, A.K.; Stukenbrok, H.

    1984-01-01

    Purified rat peritoneal and pleural mast cells preincubated briefly with radioactively labeled fatty acid were treated with A23187, which bypasses primary receptors in stimulating exocytosis. An enhanced incorporation of fatty acid into phosphatidyl choline (PC) that occurred in parallel with histamine release at 24-25 degrees C was observed and was initially proportional to the total amount of histamine discharged. Enhanced PC labeling and histamine secretion were also proportional at temperatures ranging from 17-37 degrees C. Both radioactive linoleic and palmitic acids were incorporated selectively at the beta-position of the glycerol backbone of PC. PC labeling by [3H]choline was not detectably different in control and stimulated cells, and phosphatidic acid did not exhibit selectively enhanced beta-acylation. Thus, the stimulated labeling in A23187-treated cells may occur secondary to the action of a phospholipase A2 that favors PC as a substrate. Other peritoneal cell types exhibit a very similar A23187-stimulated selective labeling of PC. Therefore, autoradiography has been used to provide a direct demonstration that in purified preparations, mast cells are the principal cell type engaged in A23187-elicited incorporation of fatty acid into PC. The efficacy of this approach has relied on special procedures devised to obtain significantly different autoradiographic grain densities between control and stimulated preparations that can be attributed to differences in the level of [3H]palmitate-labeled PC. Preliminary tests using compound 48/80 as a secretory stimulus for mast cells have identified a similar selectively enhanced PC labeling. In either case, however, consideration of possible relationships between PC metabolism and the secretory process are premature since they have not been tested directly

  6. Patterns of Direct Projections from the Hippocampus to the Medial Septum-Diagonal Band Complex : Anterograde Tracing with Phaseolus vulgaris Leucoagglutinin Combined with Immunohistochemistry of Choline Acetyltransferase

    NARCIS (Netherlands)

    Gaykema, R.P.A.; Kuil, J. van der; Hersh, L.B.; Luiten, P.G.M.

    1991-01-01

    The projections from the Ammon's horn to the cholinergic cell groups in the medial septal and diagonal band nuclei were investigated with anterograde tracing of Phaseolus vulgaris leucoagglutinin combined with immunocytochemical detection of choline acetyltransferase, in the rat. Tracer injections

  7. Eggs early in complementary feeding increase choline pathway biomarkers and DHA: a randomized controlled trial in Ecuador.

    Science.gov (United States)

    Iannotti, Lora L; Lutter, Chessa K; Waters, William F; Gallegos Riofrío, Carlos Andres; Malo, Carla; Reinhart, Gregory; Palacios, Ana; Karp, Celia; Chapnick, Melissa; Cox, Katherine; Aguirre, Santiago; Narvaez, Luis; López, Fernando; Sidhu, Rohini; Kell, Pamela; Jiang, Xuntian; Fujiwara, Hideji; Ory, Daniel S; Young, Rebecca; Stewart, Christine P

    2017-12-01

    Background: Choline status has been associated with stunting among young children. Findings from this study showed that an egg intervention improved linear growth by a length-for-age z score of 0.63. Objective: We aimed to test the efficacy of eggs introduced early in complementary feeding on plasma concentrations of biomarkers in choline pathways, vitamins B-12 and A, and essential fatty acids. Design: A randomized controlled trial, the Lulun ("egg" in Kichwa) Project, was conducted in a rural indigenous population of Ecuador. Infants aged 6-9 mo were randomly assigned to treatment (1 egg/d for 6 mo; n = 80) and control (no intervention; n = 83) groups. Socioeconomic data, anthropometric measures, and blood samples were collected at baseline and endline. Household visits were made weekly for morbidity surveillance. We tested vitamin B-12 plasma concentrations by using chemiluminescent competitive immunoassay and plasma concentrations of choline, betaine, dimethylglycine, retinol, essential fatty acids, methionine, dimethylamine (DMA), trimethylamine, and trimethylamine- N -oxide (TMAO) with the use of liquid chromatography-tandem mass spectrometry. Results: Socioeconomic factors and biomarker concentrations were comparable at baseline. Of infants, 11.4% were vitamin B-12 deficient and 31.7% marginally deficient at baseline. In adjusted generalized linear regression modeling, the egg intervention increased plasma concentrations compared with control by the following effect sizes: choline, 0.35 (95% CI: 0.12, 0.57); betaine, 0.29 (95% CI: 0.01, 0.58); methionine, 0.31 (95% CI: 0.03, 0.60); docosahexaenoic acid, 0.43 (95% CI: 0.13, 0.73); DMA, 0.37 (95% CI: 0.37, 0.69); and TMAO, 0.33 (95% CI: 0.08, 0.58). No significant group differences were found for vitamin B-12, retinol, linoleic acid (LA), α-linolenic acid (ALA), or ratios of betaine to choline and LA to ALA. Conclusion: The findings supported our hypothesis that early introduction of eggs significantly

  8. The value of 18F-choline PET/CT in patients with elevated PSA-level and negative prostate needle biopsy for localisation of prostate cancer

    International Nuclear Information System (INIS)

    Igerc, I.; Kohlfuerst, S.; Gallowitsch, H.J.; Matschnig, S.; Kresnik, E.; Gomez-Segovia, I.; Lind, P.

    2008-01-01

    Patients with persistent elevated PSA and repeated negative prostate biopsy, that means having the prostate biopsied at multiple times, were investigated with 18F-choline PET/CT to delineate prostate cancer and guide renewed prostate biopsy. Twenty patients with elevated PSA and negative prostate biopsies underwent 18F-choline PET/CT. We performed an early examination of the pelvic region 3-5 min after application. After 30 minutes a whole body PET/CT examination was performed. Image analysis was performed visually and by semi-quantitative analysis calculating the maximum standardised uptake value (SUVmax). 18F-choline uptake was defined as focal, multifocal or inhomogeneous. After the 18F-choline PET/CT, all patients underwent a repeated prostate biopsy, and in the cases where a focal or multifocal uptake was found, the biopsy was guided by the result of the examination. Qualitative image analysis revealed focal 18F-choline uptake in 13 out of 20 patients. In five patients, prostate cancer was revealed by repeated aspiration biopsy. None of the patients with a multifocal or inhomogeneous 18F-choline uptake had a malignant neoplasm in the prostate. Semiquantitative analysis performed with SUVmax was not helpful in the discrimination of malignancy but showed high values also in benign prostate diseases, as well as in normal prostate tissue. The dual-phase protocol delivered no clear benefit in discriminating malignancy from benign alterations. The use of 18F-choline cannot be generally recommended for localising prostate cancer; however, in highly selected patients, we found useful additional information. In 25% of patients, 18F-choline PET/CT allowed the identification of neoplastic prostatic zones. (orig.)

  9. 3D-segmentation of the 18F-choline PET signal for target volume definition in radiation therapy of the prostate.

    Science.gov (United States)

    Ciernik, I Frank; Brown, Derek W; Schmid, Daniel; Hany, Thomas; Egli, Peter; Davis, J Bernard

    2007-02-01

    Volumetric assessment of PET signals becomes increasingly relevant for radiotherapy (RT) planning. Here, we investigate the utility of 18F-choline PET signals to serve as a structure for semi-automatic segmentation for forward treatment planning of prostate cancer. 18F-choline PET and CT scans of ten patients with histologically proven prostate cancer without extracapsular growth were acquired using a combined PET/CT scanner. Target volumes were manually delineated on CT images using standard software. Volumes were also obtained from 18F-choline PET images using an asymmetrical segmentation algorithm. PTVs were derived from CT 18F-choline PET based clinical target volumes (CTVs) by automatic expansion and comparative planning was performed. As a read-out for dose given to non-target structures, dose to the rectal wall was assessed. Planning target volumes (PTVs) derived from CT and 18F-choline PET yielded comparable results. Optimal matching of CT and 18F-choline PET derived volumes in the lateral and cranial-caudal directions was obtained using a background-subtracted signal thresholds of 23.0+/-2.6%. In antero-posterior direction, where adaptation compensating for rectal signal overflow was required, optimal matching was achieved with a threshold of 49.5+/-4.6%. 3D-conformal planning with CT or 18F-choline PET resulted in comparable doses to the rectal wall. Choline PET signals of the prostate provide adequate spatial information amendable to standardized asymmetrical region growing algorithms for PET-based target volume definition for external beam RT.

  10. A choline-deficient diet exacerbates fatty liver but attenuates insulin resistance and glucose intolerance in mice fed a high-fat diet.

    Science.gov (United States)

    Raubenheimer, Peter J; Nyirenda, Moffat J; Walker, Brian R

    2006-07-01

    Liver fat accumulation is proposed to link obesity and insulin resistance. To dissect the role of liver fat in the insulin resistance of diet-induced obesity, we altered liver fat using a choline-deficient diet. C57Bl/6 mice were fed a low-fat (10% of calories) or high-fat (45% of calories) diet for 8 weeks; during the final 4 weeks, diets were either choline deficient or choline supplemented. In choline replete animals, high-fat feeding induced weight gain, elevated liver triglycerides (171%), hyperinsulinemia, and glucose intolerance. Choline deficiency did not affect body or adipose depot weights but amplified liver fat accumulation with high-fat diet (281%, P insulin (from 983 +/- 175 to 433 +/- 36 pmol/l, P phosphatidylcholine synthesis and of enzymes involved in free fatty acid esterification, without affecting those of de novo lipogenesis or fatty acid oxidation. We conclude that liver fat accumulation per se does not cause insulin resistance during high-fat feeding and that choline deficiency may shunt potentially toxic free fatty acids toward innocuous storage triglyceride in the liver.

  11. Oscillatory bands, neuronal synchrony and hippocampal function: implications of the effects of prenatal choline supplementation for sleep-dependent memory consolidation.

    Science.gov (United States)

    Cheng, Ruey-Kuang; Williams, Christina L; Meck, Warren H

    2008-10-27

    Choline supplementation of the maternal diet has long-term facilitative effects on spatial and temporal memory processes in the offspring. To further delineate the impact of early nutritional status on brain and behavior, we examined effects of prenatal-choline availability on hippocampal oscillatory frequency bands in 12 month-old male and female rats. Adult offspring of time-pregnant dams that were given a deficient level of choline (DEF=0.0 g/kg), sufficient choline (CON=1.1 g/kg) or supplemental choline (SUP=3.5 g/kg) in their chow during embryonic days (ED) 12-17 were implanted with an electroencephalograph (EEG) electrode in the hippocampal dentate gyrus in combination with an electromyograph (EMG) electrode patch implanted in the nuchal muscle. Five consecutive 8-h recording sessions revealed differential patterns of EEG activity as a function of awake, slow-wave sleep (SWS) and rapid-eye movement (REM) sleep states and prenatal choline status. The main finding was that SUP rats displayed increased power levels of gamma (30-100 Hz) band oscillations during all phases of the sleep/wake cycle. These findings are discussed within the context of a general review of neuronal oscillations (e.g., delta, theta, and gamma bands) and synchronization across multiple brain regions in relation to sleep-dependent memory consolidation in the hippocampus.

  12. Improved Diagnostic Accuracy in Characterization of Adnexal Masses by Detection of Choline Peak Using 1H MR Spectroscopy in Comparison to Internal Reference at 3 Tesla.

    Science.gov (United States)

    Malek, Mahrooz; Pourashraf, Maryam; Gilani, Mitra Modares; Gity, Masoumeh

    2015-01-01

    The aim of this study was to assess the role of the presence of a choline peak in 3 Tesla 1H magnetic resonance spectroscopy (MRS) for differentiating benign from malignant adnexal masses. A total of 46 adnexal masses (23 malignant and 23 benign) underwent 1H MRS study prior to surgery to assess the presence of choline peak. A choline peak was detected in 16 malignant masses (69.5%) and was absent in the other 7 (30.5%). A choline peak was only detected in 6 (26%) of the benign adnexal masses. The presence of an MRS choline peak had a sensitivity of 69.5%, a specificity of 74%, a positive predictive value (PPV) of 72.7%, and a negative predictive value (NPV) of 71% for diagnosing malignant adnexal masses. A significant difference between the frequency of mean choline peaks in benign and malignant adnexal masses was observed (P valuepeak is seen in malignant adnexal masses more frequently than the benign masses, and may be helpful for diagnosing malignant adnexal masses.

  13. A comparison between endogenous acetylcholiner release and (3H) choline outflow from guinea-pig brain slices

    International Nuclear Information System (INIS)

    Beani, L.; Bianchi, C.; Siniscalchi, A.; Sivilotti, L.; Tanganelli, S.; Veratti, E.

    1986-01-01

    The measure of tritium-choline efflux from preloaded brain slices is considered a valid method for studying cholinergic functiton. At variance with th say of endogenous acetylcholine this procedure gives andindex of the release process in the absence of esterase inhibition, thus excluding the dampening of the autoreceptor-mediated negative feedback. In order to establish the equivalence of these approaches the tow methods have been compared on electrically=stimulated guinea-pig brain slices, kept under the ame experimental conditions. The results show that only a partial equivalence of the two methods can be recognized. A drawback of the tritium-choline approach is the exhaustion or dilution of tritium stores, so that drug-induced increases of evoked efflux are minimized

  14. Automated synthesis of 11C-carfentanil with 11C-choline module and micro PET imaging

    International Nuclear Information System (INIS)

    Zhang Jinming; Zhang Xiaojun; Tian Jiahe; Xu Zhihong; Xiang Xiaohui

    2011-01-01

    A simple modified home-made 11 C-choline module enabled to rapid and efficient synthesis 11 C-carfentanil ( 11 C-CFN) as CNS μ-opioid receptor imaging agent. The synthesis of 11 C-CFN was completed in a yield of 14.8 GBq within 18 min from 11 C-CO 2 on the choline module. The methylation took place from 4-piperidinecarboxylic acid, 4-[(1-oxopropyl) phenylamino]-l-(2-phenylethyl), sodium salt as precursor in DMSO solution. The radio- chemical yields were over 80% (n=55, decay-corrected and based on 11 CH 3 -triflate). The radiochemical purity was over 95% and the specific activities was over 1.4 × 10 14 Bq/g. The biologic activity of 11 C-CFN was confirmed with Micro PET/CT imaging. (authors)

  15. Different behaviors of single and multi wall carbon nanotubes for studying electrochemistry and electrocatalysis of choline oxidase

    International Nuclear Information System (INIS)

    Sajjadi, Sharareh; Ghourchian, Hedayatollah; Rahimi, Parvaneh

    2011-01-01

    Highlights: → In the presence of a typical room temperature ionic liquid (RTIL), Choline oxidase (ChOx) as a model enzyme was uniformly immobilized on either single or multi wall carbon nanotubes (SWCNTs or MWCNTs) covered on glassy carbon (GC) electrode, and the electron transfer and electroanalytical response of enzyme toward choline was evaluated. → ChOx on RTIL/MWCNTs/GC electrode showed higher electrical conductivity, better reversibility of redox reaction and higher electron transfer rate indicating more facile and rapid rate of electron transfer. → On the other hand, RTIL/SWCNTs/GC electrode showed higher amount of enzyme loading, higher enzyme-substrate affinity, lower detection limit, better sensitivity and wider linear range. → Consequently, MWCNTs are preferable for kinetic study of ChOx, while SWCNTs are more convenient for biosensing applications. - Abstract: This work presents a detailed comparison between single and multi wall carbon nanotubes (SWCNTs and MWCNTs) in an effort to understand which could be a better supporting material for studying the electrochemistry and electrocatalysis of enzymes. Choline oxidase (ChOx) was chosen as a model enzyme for evaluation of the electrodes' performance. The enzyme was adsorbed on either SWCNT or MWCNT modified electrode, in the presence of a typical room temperature ionic liquid (RTIL), and its electron transfer and electroanalytical response toward choline was investigated. RTIL/MWCNTs/GC electrode was uniformly covered by ChOx. Besides, higher electrical conductivity, better reversibility of the ChOx redox reaction and higher electron transfer rate of the enzyme indicated more facile and rapid rate of electron transfer. On the other hand, RTIL/SWCNTs/GC electrodes showed higher amount of enzyme loading, higher enzyme-substrate affinity, lower detection limit, better sensitivity and wider linear range. Consequently, MWCNTs are preferable for kinetic study of ChOx, while SWCNTs are more convenient

  16. The correlation between (1)H MRS choline concentrations and MR diffusion trace values in human brain tumors

    Czech Academy of Sciences Publication Activity Database

    Wagnerová, Dita; Jirů, F.; Dezortová, M.; Vargová, Lýdia; Syková, Eva; Hájek, M.

    2009-01-01

    Roč. 22, č. 1 (2009), s. 19-31 ISSN 0968-5243 R&D Projects: GA MŠk(CZ) LC554 Grant - others:MZd(CZ) MZ0IKEM2005; EC FP6 project Angiotargeting(XE) 504743 Institutional research plan: CEZ:AV0Z50390512 Keywords : spectroscopic imaging * cholines * diffusion trace Subject RIV: FH - Neurology Impact factor: 1.859, year: 2009

  17. PET and PET/CT with radiolabeled choline in prostate cancer: a critical reappraisal of 20 years of clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Giovacchini, Giampiero; Giovannini, Elisabetta; Leoncini, Rossella; Riondato, Mattia; Ciarmiello, Andrea [S. Andrea Hospital, Nuclear Medicine Department, La Spezia (Italy)

    2017-09-15

    We here aim to provide a comprehensive and critical review of the literature concerning the clinical applications of positron emission tomography/computed tomography (PET/CT) with radiolabeled choline in patients with prostate cancer (PCa). We will initially briefly summarize the historical context that brought to the synthesis of [{sup 11}C]choline, which occurred exactly 20 years ago. We have arbitrarily grouped the clinical studies in three different periods, according to the year in which they were published and according to their relation with their applications in urology, radiotherapy and oncology. Studies at initial staging and, more extensively, studies in patients with biochemical failure, as well as factors predicting positive PET/CT will be reviewed. The capability of PET/CT with radiolabeled choline to provide prognostic information on PCa-specific survival will also be examined. The last sections will be devoted to the use of radiolabeled choline for monitoring the response to androgen deprivation therapy, radiotherapy, and chemotherapy. The accuracy and the limits of the technique will be discussed according to the information available from standard validation processes, including biopsy or histology. The clinical impact of the technique will be discussed on the basis of changes induced in the management of patients and in the evaluation of the response to therapy. Current indications to PET/CT, as officially endorsed by guidelines, or as routinely performed in the clinical practice will be illustrated. Emphasis will be made on methodological factors that might have influenced the results of the studies or their interpretation. Finally, we will briefly highlight the potential role of positron emission tomography/magnetic resonance and of new radiotracers for PCa imaging. (orig.)

  18. No evidence for role of extracellular choline-acetyltransferase in generation of gamma oscillations in rat hippocampal slices in vitro.

    Science.gov (United States)

    Hollnagel, J O; ul Haq, R; Behrens, C J; Maslarova, A; Mody, I; Heinemann, U

    2015-01-22

    Acetylcholine (ACh) is well known to induce persistent γ-oscillations in the hippocampus when applied together with physostigmine, an inhibitor of the ACh degrading enzyme acetylcholinesterase (AChE). Here we report that physostigmine alone can also dose-dependently induce γ-oscillations in rat hippocampal slices. We hypothesized that this effect was due to the presence of choline in the extracellular space and that this choline is taken up into cholinergic fibers where it is converted to ACh by the enzyme choline-acetyltransferase (ChAT). Release of ACh from cholinergic fibers in turn may then induce γ-oscillations. We therefore tested the effects of the choline uptake inhibitor hemicholinium-3 (HC-3) on persistent γ-oscillations either induced by physostigmine alone or by co-application of ACh and physostigmine. We found that HC-3 itself did not induce γ-oscillations and also did not prevent physostigmine-induced γ-oscillation while washout of physostigmine and ACh-induced γ-oscillations was accelerated. It was recently reported that ChAT might also be present in the extracellular space (Vijayaraghavan et al., 2013). Here we show that the effect of physostigmine was prevented by the ChAT inhibitor (2-benzoylethyl)-trimethylammonium iodide (BETA) which could indicate extracellular synthesis of ACh. However, when we tested for effects of extracellularly applied acetyl-CoA, a substrate of ChAT for synthesis of ACh, physostigmine-induced γ-oscillations were attenuated. Together, these findings do not support the idea that ACh can be synthesized by an extracellularly located ChAT. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Choline Supplementation Prevents a Hallmark Disturbance of Kwashiorkor in Weanling Mice Fed a Maize Vegetable Diet: Hepatic Steatosis of Undernutrition

    OpenAIRE

    Thaddaeus May; Kevin C. Klatt; Jacob Smith; Eumenia Castro; Mark Manary; Marie A. Caudill; Farook Jahoor; Marta L. Fiorotto

    2018-01-01

    Hepatic steatosis is a hallmark feature of kwashiorkor malnutrition. However, the pathogenesis of hepatic steatosis in kwashiorkor is uncertain. Our objective was to develop a mouse model of childhood undernutrition in order to test the hypothesis that feeding a maize vegetable diet (MVD), like that consumed by children at risk for kwashiorkor, will cause hepatic steatosis which is prevented by supplementation with choline. A MVD was developed with locally sourced organic ingredients, and fed...

  20. Characterization of new eye drops with choline salicylate and assessment of their irritancy by in vitro short time exposure tests

    OpenAIRE

    Wroblewska, Katarzyna; Kucinska, Małgorzata; Murias, Marek; Lulek, Janina

    2015-01-01

    The aim of our study was to examine the irritation potential of new eye drops containing 2% choline salicylate (CS) as an active pharmaceutical ingredient (API) and various polymers increasing eye drop viscosity (hydroxyethylcellulose, hydroxypropyl methylcellulose, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone). The standard method for assessing the potential of irritating substances has been the Draize rabbit eye test. However the European Centre for Validation of Alternative Met...

  1. Histopathological correlation of 11C-choline PET scans for target volume definition in radical prostate radiotherapy

    International Nuclear Information System (INIS)

    Chang, Joe H.; Joon, Daryl Lim; Lee, Sze Ting; Gong, Sylvia J.; Scott, Andrew M.; Davis, Ian D.; Clouston, David; Bolton, Damien; Hamilton, Christopher S.; Khoo, Vincent

    2011-01-01

    Background and purpose: To evaluate the accuracy of 11 C-choline PET scans in defining dominant intraprostatic lesions (DILs) for radiotherapy target volume definition. Material and methods: Eight men with prostate cancer who had 11 C-choline PET scans prior to radical prostatectomy were studied. Several methods were used to contour the DIL on the PET scans: visual, PET Edge, Region Grow, absolute standardised uptake value (SUV) thresholds and percentage of maximum SUV thresholds. Prostatectomy specimens were sliced in the transverse plane and DILs were delineated on these by a pathologist. These were then compared with the PET scans. The accuracy of correlation was assessed by the Dice similarity coefficient (DSC) and the Youden index. Results: The contouring method resulting in both the highest DSC and the highest Youden index was 60% of the maximum SUV (SUV 60% ), with values of 0.64 and 0.51, respectively. However SUV 60% was not statistically significantly better than all of the other methods by either measure. Conclusions: Although not statistically significant, SUV 60% resulted in the best correlation between 11 C-choline PET and pathology amongst all the methods studied. The degree of correlation shown here is consistent with previous studies that have justified using imaging for DIL radiotherapy target volume definition.

  2. Choline-amino acid ionic liquids: past and recent achievements about the structure and properties of these really "green" chemicals.

    Science.gov (United States)

    Gontrani, Lorenzo

    2018-06-01

    The structure of choline-amino acid ionic liquids, atoxic task-specific solvents composed of materials originated from renewable feedstocks, is reviewed in this letter. The varied and strong interactions that these liquids are capable of establishing are largely dependent on their structure and confer them outstanding solvating properties with respect to a large number of different solutes. Among the experimental methods capable of yielding structural insight, the energy-dispersive version of X-Ray diffraction, that uses the Bremsstrahlung radiation of the X-Ray tube, is a technique very well suited to investigate these liquid systems. The diffraction spectra of five choline-amino acid ionic liquids, recently measured, are reported and discussed; in particular, the presence or absence of the medium-range order pre-peak is related to the presence of polar groups within the amino acid side chain that destroys the hydrophobic interactions between aliphatic chains. In the final section, a recent example of choline-amino acid ionic liquids as for ancient paper preservation and two other interesting results are discussed at the end.

  3. The role of positron emission tomography/computed tomography imaging with radiolabeled choline analogues in prostate cancer.

    Science.gov (United States)

    Navarro-Pelayo Láinez, M M; Rodríguez-Fernández, A; Gómez-Río, M; Vázquez-Alonso, F; Cózar-Olmo, J M; Llamas-Elvira, J M

    2014-11-01

    prostate cancer is the most frequent solid malignant tumor in Western Countries. Positron emission tomography/x-ray computed tomography imaging with radiolabeled choline analogues is a useful tool for restaging prostate cancer in patients with rising prostate-specific antigen after radical treatment (in whom conventional imaging techniques have important limitations) as well as in the initial assessment of a selected group of prostate cancer patients. For this reason a literature review is necessary in order to evaluate the usefulness of this imaging test for the diagnosis and treatment of prostate cancer. a MEDLINE (PubMed way) literature search was performed using the search parameters: «Prostate cancer» and «Choline-PET/CT». Other search terms were «Biochemical failure» and/or «Staging» and/or «PSA kinetics». English and Spanish papers were selected; original articles, reviews, systematic reviews and clinical guidelines were included. according to available data, radiolabeled choline analogues plays an important role in the management of prostate cancer, especially in biochemical relapse because technique accuracy is properly correlated with prostate-specific antigen values and kinetics. Although is an emerging diagnostic technique useful in treatment planning of prostate cancer, final recommendations have not been submitted. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  4. Crystallization and preliminary X-ray diffraction studies of choline-binding protein F from Streptococcus pneumoniae

    Energy Technology Data Exchange (ETDEWEB)

    Molina, Rafael [Grupo de Cristalografía Macromolecular y Biología Estructural, Instituto Química Física Rocasolano, CSIC, Serrano 119, 28006 Madrid (Spain); González, Ana; Moscoso, Miriam; García, Pedro [Departamento de Microbiología Molecular, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain); Stelter, Meike; Kahn, Richard [Institut de Biologie Structurale J.-P. Ebel CEA CNRS UJF, Laboratoire de Cristallographie Macromoléculaire, 41 Rue Jules Horowitz, 38027 Grenoble CEDEX 1 (France); Hermoso, Juan A., E-mail: xjuan@iqfr.csic.es [Grupo de Cristalografía Macromolecular y Biología Estructural, Instituto Química Física Rocasolano, CSIC, Serrano 119, 28006 Madrid (Spain)

    2007-09-01

    The modular choline-binding protein F (CbpF) from S. pneumoniae has been crystallized by the hanging-drop vapour-diffusion method. A SAD data set from a gadolinium-complex derivative has been collected to 2.1 Å resolution. Choline-binding protein F (CbpF) is a modular protein that is bound to the pneumococcal cell wall through noncovalent interactions with choline moieties of the bacterial teichoic and lipoteichoic acids. Despite being one of the more abundant proteins on the surface, along with the murein hydrolases LytA, LytB, LytC and Pce, its function is still unknown. CbpF has been crystallized using the hanging-drop vapour-diffusion method at 291 K. Diffraction-quality orthorhombic crystals belong to space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 49.13, b = 114.94, c = 75.69 Å. A SAD data set from a Gd-HPDO3A-derivatized CbpF crystal was collected to 2.1 Å resolution at the gadolinium L{sub III} absorption edge using synchrotron radiation.

  5. Crystallization and preliminary X-ray diffraction studies of choline-binding protein F from Streptococcus pneumoniae

    International Nuclear Information System (INIS)

    Molina, Rafael; González, Ana; Moscoso, Miriam; García, Pedro; Stelter, Meike; Kahn, Richard; Hermoso, Juan A.

    2007-01-01

    The modular choline-binding protein F (CbpF) from S. pneumoniae has been crystallized by the hanging-drop vapour-diffusion method. A SAD data set from a gadolinium-complex derivative has been collected to 2.1 Å resolution. Choline-binding protein F (CbpF) is a modular protein that is bound to the pneumococcal cell wall through noncovalent interactions with choline moieties of the bacterial teichoic and lipoteichoic acids. Despite being one of the more abundant proteins on the surface, along with the murein hydrolases LytA, LytB, LytC and Pce, its function is still unknown. CbpF has been crystallized using the hanging-drop vapour-diffusion method at 291 K. Diffraction-quality orthorhombic crystals belong to space group P2 1 2 1 2, with unit-cell parameters a = 49.13, b = 114.94, c = 75.69 Å. A SAD data set from a Gd-HPDO3A-derivatized CbpF crystal was collected to 2.1 Å resolution at the gadolinium L III absorption edge using synchrotron radiation

  6. Effects of rumen-protected choline supplementation on metabolic and performance responses of transition dairy cows.

    Science.gov (United States)

    Leiva, T; Cooke, R F; Brandão, A P; Marques, R S; Vasconcelos, J L M

    2015-04-01

    The objective of this experiment was to compare metabolic and milk production parameters in dairy cows supplemented and nonsupplemented with rumen-protected choline (RPC) during the transition period. Twenty-three nonlactating, multiparous, pregnant Holstein cows were ranked by BW and BCS 21 d before expected date of calving and immediately were assigned to receive (n = 12) or not receive (control; n = 11) RPC until 45 d in milk (DIM). Cows supplemented with RPC received (as-fed basis) 50 and 100 g/d of RPC (18.8% choline) before and after calving, respectively. Before calving, cows were maintained in 2 drylot pens according to treatment with ad libitum access to corn silage, and individually they received (as-fed basis) 3 kg/cow daily of a concentrate. Upon calving, cows were moved to 2 adjacent drylot pens according to treatment, milked twice daily, offered (as-fed basis) 35 kg/cow daily of corn silage, and individually received a concentrate formulated to meet their nutritional requirements after milking. The RPC was individually offered to cows as a topdressing into the morning concentrate feeding. Before calving, cow BW and BCS were recorded weekly, and blood samples were collected every 5 d beginning on d -21 relative to expected calving date. Upon calving and until 45 DIM, BW and BCS were recorded weekly, individual milk production was recorded daily, and milk samples were collected once a week and analyzed for fat, protein, and total solids. Blood samples were collected every other day from 0 to 20 DIM and every 5 d from 20 to 45 DIM. Based on actual calving dates, cows receiving RPC or control began receiving treatments 16.8 ± 1.7 and 17.3 ± 2.0 d before calving, respectively. No treatment effects were detected (P ≥ 0.18) on postpartum concentrate intake, BW and BCS, or serum concentrations of cortisol, β-hydroxybutyrate, NEFA, glucose, and IGF-I. Cows supplemented with RPC had greater (P ≤ 0.01) mean serum haptoglobin and insulin concentrations

  7. Plasma immune protein analysis in the orange-spotted grouper Epinephelus coioides: Evidence for altered expressions of immune factors associated with a choline-supplemented diet.

    Science.gov (United States)

    Shiu, Ya-Li; Chiu, Kuo-Hsun; Huynh, Truong-Giang; Liu, Ping-Chung; Liu, Chun-Hung

    2017-06-01

    This study aimed to unravel the regulatory roles of choline in activating immune responses and disease resistance of the orange-spotted grouper Epinephelus coioides. Fish were fed a choline-supplemented diet at 1 g kg -1 of feed for 30 days. Fish fed a fish meal basal diet without choline-supplement served as controls. At the end of the feeding trial, fish were challenged with Vibrio alginolyticus. Meanwhile, plasma proteomics of fish in each group were also evaluated by two-dimensional gel electrophoresis (2-DE), and differentially expressed proteins were identified by tandem mass spectrophotometry (MS/MS), then a Western blot analysis or real-time polymerase chain reaction was used to confirm differential expressions of immune-enhancing proteins. Results showed that choline significantly increased survival of E. coioides 48 days after being injected with V. alginolyticus. From maps of plasma proteins, a comparative analysis between the control and choline groups revealed that 111 spots matched, with 26 altered expression spots in the choline group. Of these 26 spots, 16 were upregulated and 10 downregulated. After protein identification by reverse-phase nano-high-performance liquid chromatography-electrospray ionization MS/MS analysis, eight of 26 proteins were found to be immune-related proteins, all of which were upregulated, including complement 3 (C3), alpha-2-macroglobulin-P-like isoform (A2M), fibrinogen beta chain precursor (FBG), and immunoglobulin heavy constant mu (Ighm) proteins. Expression of the A2M protein and A2M enzyme activity in plasma of fish fed choline significantly increased compared to the control group. Additionally, A2M messenger (m)RNA transcripts were also upregulated in the liver and kidneys. Significantly higher C3 expressions at both the mRNA and protein levels were detected in the liver of fish in the choline group. Moreover, FBG gene expressions in the liver and kidneys significantly increased, while Ighm increased in the

  8. [{sup 11}C]Choline PET/CT detection of bone metastases in patients with PSA progression after primary treatment for prostate cancer: comparison with bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Picchio, Maria [San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); National Research Council (IBFM-CNR), Institute for Bioimaging and Molecular Physiology, Milan (Italy); Spinapolice, Elena Giulia; Crivellaro, Cinzia [University of Milano-Bicocca, Center for Molecular Bioimaging, Milan (Italy); Fallanca, Federico; Gianolli, Luigi [San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); Giovacchini, Giampiero [University of Milano-Bicocca, Center for Molecular Bioimaging, Milan (Italy); University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Messa, Cristina [National Research Council (IBFM-CNR), Institute for Bioimaging and Molecular Physiology, Milan (Italy); University of Milano-Bicocca, Center for Molecular Bioimaging, Milan (Italy); San Gerardo Hospital, Department of Nuclear Medicine, Monza (Italy)

    2012-01-15

    The aim of this study was to evaluate the clinical usefulness of [{sup 11}C]choline positron emission tomography (PET)/CT in comparison with bone scintigraphy (BS) in detecting bone metastases (BM) of patients with biochemical progression after radical treatment for prostate cancer (PCa). Seventy-eight consecutive patients with biochemical progression of PCa (mean prostate-specific antigen 21.1 ng/ml, range 0.2-500.0 ng/ml) referred for both [{sup 11}C]choline PET/CT and BS for restaging purposes were retrospectively analysed. The diagnostic accuracy of [{sup 11}C]choline PET/CT and BS was assessed by using morphological imaging and/or follow-up as standards of reference. As equivocal findings were found, the accuracy analysis was performed twice, once including them as positive and once as negative. A separate analysis was also performed in hormone-resistant patients and data compared with those of patients who did not receive anti-androgenic treatment. Equivocal findings occurred in 1 of 78 (1%) cases in [{sup 11}C]choline PET/CT and in 21 of 78 (27%) cases in BS. Depending on their attribution as either positive or negative, the ranges of sensitivity, specificity, positive predictive value, negative predictive value and accuracy for [{sup 11}C]choline PET/CT were 89-89%, 98-100%, 96-100%, 94-96% and 95-96%, respectively. For BS they were 100-70%, 75-100%, 68-100%, 100-86% and 83-90%, respectively. Concordant findings between [{sup 11}C]choline PET/CT and BS occurred in 55 of 78 (71%) cases. The accuracy of [{sup 11}C]choline PET/CT did not significantly (p = 0.30) differ between hormone-resistant patients (97%) and those who did not receive anti-androgenic treatment (95%). In clinical practice, [{sup 11}C]choline PET/CT may not replace BS because of its lower sensitivity. However, for its high specificity, [{sup 11}C]choline PET/CT positive findings may accurately predict the presence of BM. Equivocal findings are more frequent in BS than [{sup 11}C]choline PET

  9. Effects of choline chloride on electrodeposited Ni coating from a Watts-type bath

    Science.gov (United States)

    Wang, Yurong; Yang, Caihong; He, Jiawei; Wang, Wenchang; Mitsuzak, Naotoshi; Chen, Zhidong

    2016-05-01

    Electrodeposition of bright nickel (Ni) was carried out in a Watts-type bath. Choline chloride (ChCl) was applied as a multifunctional additive and substitute for nickel chloride (NiCl2) in a Watts-type bath. The function of ChCl was investigated through conductivity tests, anodic polarization, and cathodic polarization experiments. The studies revealed that ChCl performed well as a conducting salt, anodic activator, and cathodic inhibitor. The effects of ChCl on deposition rate, preferred orientation, grain size, surface morphology, and microhardness of Ni coatings were also studied. The deposition rate reached a maximum value of greater than 27 μm h-1 when 20 g L-1 ChCl was introduced to the bath. Using X-ray diffraction, it was confirmed that progressive addition of ChCl promoted the preferred crystal orientation modification from (2 0 0) and (2 2 0) to (1 1 1), refined grain size, and enhanced microhardness. The presence of ChCl lowered the roughness of the coating.

  10. Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Unconditioned Fear in Rats with Amygdala Injury

    Directory of Open Access Journals (Sweden)

    Kyungha Shin

    2016-01-01

    Full Text Available Amygdala is involved in the fear memory that recognizes certain environmental cues predicting threatening events. Manipulation of neurotransmission within the amygdala affects the expression of conditioned and unconditioned emotional memories such as fear freezing behaviour. We previously demonstrated that F3.ChAT human neural stem cells (NSCs overexpressing choline acetyltransferase (ChAT improve cognitive function of Alzheimer’s disease model rats with hippocampal or cholinergic nerve injuries by increasing acetylcholine (ACh level. In the present study, we examined the effect of F3.ChAT cells on the deficit of unconditioned fear freezing. Rats given N-methyl-d-aspartate (NMDA in their amygdala 2 weeks prior to cat odor exposure displayed very short resting (freezing time compared to normal animals. NMDA induced neuronal degeneration in the amygdala, leading to a decreased ACh concentration in cerebrospinal fluid. However, intracerebroventricular transplantation of F3.ChAT cells attenuated amygdala lesions 4 weeks after transplantation. The transplanted cells were found in the NMDA-injury sites and produced ChAT protein. In addition, F3.ChAT-receiving rats recuperated freezing time staying remote from the cat odor source, according to the recovery of brain ACh concentration. The results indicate that human NSCs overexpressing ChAT may facilitate retrieval of unconditioned fear memory by increasing ACh level.

  11. Insulin stimulates choline acetyltransferase activity in cultured embryonic chicken retina neurons

    International Nuclear Information System (INIS)

    Kyriakis, J.M.; Hausman, R.E.; Peterson, S.W.

    1987-01-01

    The effect of insulin on the appearance of the enzyme choline acetyltransferase in embryonic chicken retina neurons cultured in defined medium was studied. In the presence of a minimal level of insulin (1 ng/ml), ChoAcT activity increased with time in culture. A correspondence between the insulin concentration in the defined medium (1-100 ng/ml) and both the rate of increase and maximum attained level of ChoAcT activity was observed. Maximal ChoAcT activity was 2- to 3-fold greater in cells cultured in the presence of 100 ng of insulin per ml than in cells cultured in the presence of 1 ng of insulin per ml. To elicit maximum ChoAcT activity, insulin at 100 ng/ml was required in the medium for only the first 4 days of the culture period, at which time insulin could be reduced to maintenance levels (10 ng/ml) without affecting ChoAcT activity. Insulin binding assays performed during a 7-day culture period revealed that irrespective of the 125 I-insulin concentration in the medium during culture, cell-surface insulin receptors decreased by ≅ 90% between 4 and 7 days in culture. This decrease in insulin binding corresponded to the observed decrease in the sensitivity of ChoAcT activity to insulin. The findings suggest that insulin plays a role in mediating cholinergic differentiation in the embryonic chicken retina

  12. Novel Small Molecule Inhibitors of Choline Kinase Identified by Fragment-Based Drug Discovery.

    Science.gov (United States)

    Zech, Stephan G; Kohlmann, Anna; Zhou, Tianjun; Li, Feng; Squillace, Rachel M; Parillon, Lois E; Greenfield, Matthew T; Miller, David P; Qi, Jiwei; Thomas, R Mathew; Wang, Yihan; Xu, Yongjin; Miret, Juan J; Shakespeare, William C; Zhu, Xiaotian; Dalgarno, David C

    2016-01-28

    Choline kinase α (ChoKα) is an enzyme involved in the synthesis of phospholipids and thereby plays key roles in regulation of cell proliferation, oncogenic transformation, and human carcinogenesis. Since several inhibitors of ChoKα display antiproliferative activity in both cellular and animal models, this novel oncogene has recently gained interest as a promising small molecule target for cancer therapy. Here we summarize our efforts to further validate ChoKα as an oncogenic target and explore the activity of novel small molecule inhibitors of ChoKα. Starting from weakly binding fragments, we describe a structure based lead discovery approach, which resulted in novel highly potent inhibitors of ChoKα. In cancer cell lines, our lead compounds exhibit a dose-dependent decrease of phosphocholine, inhibition of cell growth, and induction of apoptosis at low micromolar concentrations. The druglike lead series presented here is optimizable for improvements in cellular potency, drug target residence time, and pharmacokinetic parameters. These inhibitors may be utilized not only to further validate ChoKα as antioncogenic target but also as novel chemical matter that may lead to antitumor agents that specifically interfere with cancer cell metabolism.

  13. Toxicity profile of choline chloride-based deep eutectic solvents for fungi and Cyprinus carpio fish.

    Science.gov (United States)

    Juneidi, Ibrahim; Hayyan, Maan; Mohd Ali, Ozair

    2016-04-01

    An investigation on the toxicological assessment of 10 choline chloride (ChCl)-based deep eutectic solvents (DESs) towards four fungi strains and Cyprinus carpio fish was conducted. ChCl was combined with materials from different chemical groups such as alcohols, sugars, acids and others to form DESs. The study was carried out on the individual DES components, their aqueous mixture before DES formation and their formed DESs. The agar disc diffusion method was followed to investigate their toxicity on four fungi strains selected as a model of eukaryotic microorganisms (Phanerochaete chrysosporium, Aspergillus niger, Lentinus tigrinus and Candida cylindracea). Among these DESs, ChCl:ZnCl2 exhibited the highest inhibition zone diameter towards the tested fungi growth in vitro, followed by the acidic group (malonic acid and p-toluenesulfonic acid). Another study was conducted to test the acute toxicity and determine the lethal concentration at 50 % (LC50) of the same DESs on C. carpio fish. The inhibition range and LC50 of DESs were found to be different from their individual components. DESs were found to be less toxic than their mixture or individual components. The LC50 of ChCl:MADES is much higher than that of ChCl:MAMix. Moreover, the DESs acidic group showed a lower inhibition zone on fungi growth. Thus, DESs should be considered as new components with different physicochemical properties and toxicological profiles, and not merely compositions of compounds.

  14. Positive correlations between cerebral choline and renal dysfunction in chronic renal failure

    International Nuclear Information System (INIS)

    Sasaki, Osamu; Nakahama, Hajime; Nakamura, Satoko; Inenaga, Takashi; Kawano, Yuhei; Hattori, Noriaki; Inoue, Noriko; Sawada, Tohru; Kohno, Shigeru

    2006-01-01

    Cerebral metabolism in chronic renal failure (CRF) patients has not been fully evaluated. This study examined cerebral metabolites in CRF, using proton magnetic resonance spectroscopy (MRS). Subjects comprised 19 CRF patients and 21 healthy volunteers. Spectra were acquired from voxels of interest positioned in the parietal gray and white matter, and concentrations of the following cerebral metabolites were measured: N-acetyl group (NA), creatine + phosphocreatine (Cr), choline-containing compounds (Cho), myo-inositol and glutamate + glutamine. Among the 19 CRF patients, 9 who were started on hemodialysis (HD) underwent careful follow-up. Proton MRS was performed before and about 2 weeks after starting HD. In six patients in whom follow-up was possible, a third MRS was performed after about 18 months. The NA/Cr ratio was not significantly changed in CRF. However, elevations in the Cho/Cr ratio were found in both gray and white matter compared with controls. To the best of our knowledge, this is the first report of positive correlations between the Cho/Cr ratio in both regions and serum osmotic pressure. (orig.)

  15. Phosphatidylcholine synthesis in the rat: The substrate for methylation and regulation by choline

    International Nuclear Information System (INIS)

    Datko, A.H.; Aksamit, R.R.; Mudd, S.H.

    1990-01-01

    Two lines of evidence led us to reexamine the possibility that methylation of phosphoethanolamine and its partially methylated derivatives, in addition to methylation of the corresponding phosphatidyl derivatives, plays a role in mammalian phosphatidylcholine biosynthesis: (a) Results obtained by Salerno and Beeler with rat appear to strongly support such a role for methylation of phosphobases; (b) Such reactions have recently been shown to play major roles in phosphatidylcholine synthesis by higher plants. We found that, following continuous labeling of rat liver with L-[methyl-3H]methionine for 10.4 min (intraperitoneal administration) or for 0.75 min (intraportal administration), virtually no 3H was detected in methylated derivatives of phosphoethanolamine, but readily detectable amounts of 3H were present in the base moiety of each methylated derivative of phosphatidylethanolamine. Thus, there was no indication that phospho-base methylation makes a significant contribution. Studies of cultured rat hepatoma cells showed definitively for the first time in a mammalian system that choline deprivation up-regulates the rate of flow of methyl groups originating in methionine into phosphatidylethanolamine and derivatives. Even under these conditions, methylation of phosphoethanolamine bases appeared to play a negligible role

  16. A choline derivate-modified nanoprobe for glioma diagnosis using MRI

    Science.gov (United States)

    Li, Jianfeng; Huang, Shixian; Shao, Kun; Liu, Yang; An, Sai; Kuang, Yuyang; Guo, Yubo; Ma, Haojun; Wang, Xuxia; Jiang, Chen

    2013-04-01

    Gadolinium (Gd) chelate contrast-enhanced magnetic resonance imaging (MRI) is a preferred method of glioma detection and preoperative localisation because it offers high spatial resolution and non-invasive deep tissue penetration. Gd-based contrast agents, such as Gd-diethyltriaminepentaacetic acid (DTPA-Gd, Magnevist), are widely used clinically for tumor diagnosis. However, the Gd-based MRI approach is limited for patients with glioma who have an uncompromised blood-brain barrier (BBB). Moreover, the rapid renal clearance and non-specificity of such contrast agents further hinders their prevalence. We present a choline derivate (CD)-modified nanoprobe with BBB permeability, glioma specificity and a long blood half-life. Specific accumulation of the nanoprobe in gliomas and subsequent MRI contrast enhancement are demonstrated in vitro in U87 MG cells and in vivo in a xenograft nude model. BBB and glioma dual targeting by this nanoprobe may facilitate precise detection of gliomas with an uncompromised BBB and may offer better preoperative and intraoperative tumor localization.

  17. Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency.

    Science.gov (United States)

    Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Fujita, Akira; Niitsu, Hiroaki; Hayashi, Ryohei; Hyogo, Hideyuki; Hinoi, Takao; Kitadai, Yasuhiko; Chayama, Kazuaki

    2017-01-01

    Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet. The gene expression pattern of the chemokine receptor CXCR6, which promotes NKT cell accumulation, varied between colon and liver in a manner dependent on the changes in the type II NKT cell levels. To examine the role of type II NKT cells in colitis under choline-deficient conditions, we assessed the severity of DSS-induced colitis in type I NKT cell-deficient (Jα18-/-) or type I and type II NKT cell-deficient (CD1d-/-) mice fed the MCD or CTR diets. The MCD diet led to amelioration of inflammation, decreases in interferon (IFN)-γ and interleukin (IL)-4 secretion, and a decrease in the number of IFN-γ and IL-4-producing NKT cells in Jα18-/- mice but not in CD1d-/- mice. Finally, adaptive transfer of lymphocytes with type II NKT cells exacerbated DSS-induced colitis in Jα18-/- mice with MCD diet. These results suggest that choline deficiency causes proinflammatory type II NKT cell loss and alleviates DSS-induced colitis. Thus, inflammation in DSS-induced colitis under choline deficiency is caused by type II NKT cell-dependent mechanisms, including decreased type II NKT cell and proinflammatory cytokine levels.

  18. Effect of hypoxia on the uptake of [methyl-3H]choline, [1-14C] acetate and [18F]FDG in cultured prostate cancer cells

    International Nuclear Information System (INIS)

    Hara, Toshihiko; Bansal, Aditya; DeGrado, Timothy R.

    2006-01-01

    Introduction: Choline, acetate and glucose ([2- 18 F]fluoro-2-deoxyglucose, [ 18 F]FDG) analogs are under investigation as positron emission tomography (PET) tracers for the imaging of prostate cancer; however, their response to tumor hypoxia has not been clarified. Methods: The uptake of [methyl- 3 H]choline, [1- 14 C]acetate and [ 18 F]FDG was monitored in androgen-independent PC-3 cells and androgen-sensitive LNCaP cells under aerobic or anoxic conditions. The effect of androgen depletion was also examined. Results: PC-3 cells exhibited aerobic choline and acetate uptake five to six times higher than FDG uptake, whereas LNCaP cells showed choline uptake 2.2-fold higher than acetate uptake and 10-fold higher than FDG uptake. After 4 h of anoxia, PC-3 cells showed an 85% increase in FDG uptake, a 15% decrease in choline uptake and a 36% increase in acetate uptake, whereas LNCaP cells showed a 212% increase in FDG uptake, a 28% decrease in choline uptake and no change in acetate uptake. Androgen depletion resulted in a marked decrease in the uptake of all tracers in LNCaP cells but no changes in PC-3 cells. Conclusion: In aerobic conditions, both PC-3 and LNCaP cells exhibited an order of uptake preference as follows: choline>acetate>FDG. In hypoxic cells, the order is reversed, reflecting diverse biochemical responses to hypoxia. These findings may help to explain PET imaging findings of the diverse responses of these tracers in different stages and locations of prostate cancer. Androgen depletion markedly suppressed the uptake of all three tracers in LNCaP cells, which suggests the potential for underestimation of the disease state when PET imaging is performed subsequent to antiandrogen therapy

  19. Quantification of acetylcholine, choline, betaine, and dimethylglycine in human plasma and urine using stable-isotope dilution ultra performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Kirsch, Susanne H; Herrmann, Wolfgang; Rabagny, Yannick; Obeid, Rima

    2010-12-15

    Disorders in choline metabolism are related to disease conditions. We developed a stable-isotope dilution ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of acetylcholine (ACh), betaine, choline, and dimethylglycine (DMG). We used this method to measure concentrations of the analytes in plasma and urine in addition to other biological fluids after a protein precipitation by acetonitrile. The detection limits were between 0.35 nmol/L (for ACh in urine) and 0.34 μmol/L (for betaine in urine). ACh concentrations were not detectable in plasma. Intraassay and interassay coefficient of variation (CVs) were all DMG in cerebrospinal fluid (CV=12.44%). Mean recoveries in urine pool samples were between 99.2% and 103.9%. The urinary excretion of betaine, choline, and DMG was low, with approximately 50.0% higher excretion of choline in females compared to males. Median urinary excretion of ACh were 3.44 and 3.92 μmol/mol creatinine in males and females, respectively (p=0.689). Plasma betaine concentrations correlated significantly with urinary excretions of betaine (r=0.495, p=0.027) and choline (r=0.502, p=0.024) in females. Plasma choline concentrations correlated significantly with urinary excretion of ACh in males (r=0.419, p=0.041) and females (r=0.621, p=0.003). The new method for the simultaneous determination of ACh, betaine, choline, and DMG is sensitive, precise, and fast enough to be used in clinical investigations related to the methylation pathway. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Correlation between 11C-choline or 18F-FDG uptake and tumor proliferation: a rabbit bearing lung cancer model study

    International Nuclear Information System (INIS)

    Li Yajun; Bai Renju; Gao Shuo; Li Yansheng; Liu Lei; Jia Wei; Cai Li; Xing Xiling

    2009-01-01

    Objective: Tumor proliferative activity has been recognized as an indicator of malignant degree in lung cancer and related to prognosis. The purpose of this study was to evaluate the feasibility of assessing proliferative activity with 11 C-choline and 18 F-fluorodeoxyglucose (FDG) PET on a rabbit bearing lung VX2 tumor model. Methods: About 0.5 ml of viable VX2 tumor cell suspension was slowly injected into the right lungs of 54 New Zealand white rabbits through a transthoracical needle insertion. 11 C-choline and 18 F-FDG PET scan were performed 10-11 d after tumor implantation. One ear vein was cannulated for administration of the tracers, 11 C-choline PET scan (with Discovery LS PET/CT scanner, GE) was performed 5 rain after intravenously injection of 37 MBq 11 C-choline. Then 18.7 MBq 18 F-FDG was infused at 60 min after 11 C-choline administration and 18 F-FDG PET scan was performed at 60 min after 18 F-FDG administration. The maximal standardized uptake value of tumor was calculated. The animals were euthanized after examination. Histochemical stain with proliferating cell nuclear antigen (PCNA) was performed and PCNA index was obtained to assess tumor proliferation. The difference of 11 C-choline and 18 F-FDG was analyzed using paired student t-test. The correlation of 11 C-choline 18 F-FDG and tumor cell density and PCNA index was analyzed using Pearson linear regression. Results: Of the 54 rabbits, 36 had a solitary pulmonary tumor. The rate of successful generation of a solitary VX2 tumor was 66.7% (36/54). Only 33 rabbits underwent both 11 C-choline and 18 F-FDG PET, and enrolled in this study. The mean cellular density was (547.36 ± 64.78) cells/field and the mean PCNA index was (42.34 ± 15.26)%. 18 F-FDG was higher than 11 C-choline (5.70 ± 3.45 vs 4.02 ± 3.07, t=-3.188, P=0.003). 11 C-choline significantly and positively correlated with PCNA index (r=0.786, P 11 C-choline and tumor cellular density (r=-0.176, P=0.327). 18 F-FDG significantly and

  1. 11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma

    Directory of Open Access Journals (Sweden)

    Ambrosini Valentina

    2007-06-01

    Full Text Available Abstract Background Multiple Myeloma (MM is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS, Magnetic resonance (MR and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40% had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20% had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40% had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042. Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8. Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.

  2. [A machine learning model using gut microbiome data for predicting changes of trimethylamine-N-oxide in healthy volunteers after choline consumption].

    Science.gov (United States)

    Lu, Jun-Qi; Wang, Shan; Yin, Jia; Wu, Shan; He, Yan; Zheng, Hui-Min; Sheng, Hua-Fang; Zhou, Hong-Wei

    2017-03-20

    To establish a machine learning model based on gut microbiota for predicting the level of trimethylamine N-oxide (TMAO) metabolism in vivo after choline intake to provide guidance of individualized precision diet and evidence for screening population at high risks of cardiovascular disease. We quantified plasma levels of TMAO in 18 healthy volunteers before and 8 h after a choline challenge (ingestion of two boiled eggs). The volunteers were divided into two groups with increased or decreased TMAO level following choline challenge. Fresh fecal samples were collected before taking fasting blood samples for amplifying 16S rRNA V4 tags, and the PCR products were sequenced using the platform of Illumina HiSeq 2000. The differences in gut microbiata between subjects with increased and decreased plasma TMAO were analyzed using QIIME. Based on the gut microbiota data and TMAO levels in the two groups, the prediction model was established using the machine learning random forest algorithm, and the validity of the model was tested using a verified dataset. An obvious difference was found in beta diversity of the gut microbota between the subjects with increased and decreased plasma TMAO level following choline challenge. The area under the curve (AUC) of the model was 86.39% (95% CI: 72.7%-100%). Using the verified dataset, the model showed a much higher probability for correctly predicting TMAO variation following choline challenge. The model is feasible and reliable for predicting the level of TMAO metabolism in vivo based on gut microbiota.

  3. The physicochemical and thermodynamic properties of the choline chloride-based deep eutectic solvents

    Directory of Open Access Journals (Sweden)

    Troter Dragan Z.

    2017-01-01

    Full Text Available This paper reports the physicochemical (density, dynamic viscosity, electrical conductivity and refractive index and the thermodynamic (thermal expansion coefficient, molecular volume, lattice energy and heat capacity properties of several choline chloride (ChCl based deep eutectic solvents (DESs, with 1:2 mole ratio, respectively: ChCl:propylene glycol, ChCl:1,3-dimethylurea and ChCl:thiourea, at atmospheric pressure as a function of temperature over the range of 293.15–363.15 K. Their properties were also compared with those of some already characterized ChCl-based DESs, namely ChCl:ethylene glycol, ChCl:glycerol and ChCl:urea (1:2 mole ratio. Density, viscosity and refractive index of all DESs decrease with the increasing temperature while the electrical conductivity increases. Viscosity and conductivity of the tested DESs were fitted by both Arrhenius-type and Vogel–Tamman–Fulcher equations. The changes of molar enthalpy, entropy and Gibbs energy of activation, determined using the Eyring theory, demonstrated the interactional factor as predominant over the structural factor for all DES systems. The fractional Walden rule, used to correlate molar conductivity and viscosity, showed an excellent linear behaviour. It was shown that ChCl:propylene glycol DES had properties similar to ChCl:ethylene glycol and ChCl:glycerol DESs. However, the properties (density, viscosity and electrical conductivity of ChCl:1,3-dimethylurea and ChCl: :thiourea DESs were inferior to those of the ChCl:urea DES. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III 45001

  4. Choline kinase alpha and hexokinase-2 protein expression in hepatocellular carcinoma: association with survival.

    Directory of Open Access Journals (Sweden)

    Sandi A Kwee

    Full Text Available PURPOSE: Hexokinase-2 (HK2 and more recently choline kinase alpha (CKA expression has been correlated with clinical outcomes in several major cancers. This study examines the protein expression of HK2 and CKA in hepatocellular carcinoma (HCC in association with patient survival and other clinicopathologic parameters. METHODS: Immunohistochemical analysis for HK2 and CKA expression was performed on a tissue microarray of 157 HCC tumor samples. Results were analyzed in relation to clinicopathologic data from Surveillance, Epidemiology, and End-Results Program registries. Mortality rates were assessed by Kaplan-Meier estimates and compared using log-rank tests. Predictors of overall survival were assessed using proportional hazards regression. RESULTS: Immunohistochemical expression of HK2 and CKA was detected in 71 (45% and 55 (35% tumor samples, respectively. Differences in tumor HK2 expression were associated with tumor grade (p = 0.008 and cancer stage (p = 0.001, while CKA expression differed significantly only across cancer stage (p = 0.048. Increased mortality was associated with tumor HK2 expression (p = 0.003 as well as CKA expression (p = 0.03 with hazard ratios of 1.86 (95% confidence interval (CI 1.23-2.83 and 1.59 (95% CI 1.04-2.41, respectively. Similar effects on overall survival were noted in a subset analysis of early stage (I and II HCC. Tumor HK2 expression, but not CKA expression, remained a significant predictor of survival in multivariable analyses. CONCLUSION: HK2 and CKA expression may have biologic and prognostic significance in HCC, with tumor HK2 expression being a potential independent predictor of survival.

  5. Choline Kinase Alpha as an Androgen Receptor Chaperone and Prostate Cancer Therapeutic Target

    Science.gov (United States)

    Asim, Mohammad; Massie, Charles E.; Orafidiya, Folake; Pértega-Gomes, Nelma; Warren, Anne Y.; Esmaeili, Mohsen; Selth, Luke A.; Zecchini, Heather I.; Luko, Katarina; Qureshi, Arham; Baridi, Ajoeb; Menon, Suraj; Madhu, Basetti; Escriu, Carlos; Lyons, Scott; Vowler, Sarah L.; Zecchini, Vincent R.; Shaw, Greg; Hessenkemper, Wiebke; Russell, Roslin; Mohammed, Hisham; Stefanos, Niki; Lynch, Andy G.; Grigorenko, Elena; D’Santos, Clive; Taylor, Chris; Lamb, Alastair; Sriranjan, Rouchelle; Yang, Jiali; Stark, Rory; Dehm, Scott M.; Rennie, Paul S.; Carroll, Jason S.; Griffiths, John R.; Tavaré, Simon; Mills, Ian G.; McEwan, Iain J.; Baniahmad, Aria; Tilley, Wayne D.; Neal, David E.

    2016-01-01

    Background: The androgen receptor (AR) is a major drug target in prostate cancer (PCa). We profiled the AR-regulated kinome to identify clinically relevant and druggable effectors of AR signaling. Methods: Using genome-wide approaches, we interrogated all AR regulated kinases. Among these, choline kinase alpha (CHKA) expression was evaluated in benign (n = 195), prostatic intraepithelial neoplasia (PIN) (n = 153) and prostate cancer (PCa) lesions (n = 359). We interrogated how CHKA regulates AR signaling using biochemical assays and investigated androgen regulation of CHKA expression in men with PCa, both untreated (n = 20) and treated with an androgen biosynthesis inhibitor degarelix (n = 27). We studied the effect of CHKA inhibition on the PCa transcriptome using RNA sequencing and tested the effect of CHKA inhibition on cell growth, clonogenic survival and invasion. Tumor xenografts (n = 6 per group) were generated in mice using genetically engineered prostate cancer cells with inducible CHKA knockdown. Data were analyzed with χ2 tests, Cox regression analysis, and Kaplan-Meier methods. All statistical tests were two-sided. Results: CHKA expression was shown to be androgen regulated in cell lines, xenografts, and human tissue (log fold change from 6.75 to 6.59, P = .002) and was positively associated with tumor stage. CHKA binds directly to the ligand-binding domain (LBD) of AR, enhancing its stability. As such, CHKA is the first kinase identified as an AR chaperone. Inhibition of CHKA repressed the AR transcriptional program including pathways enriched for regulation of protein folding, decreased AR protein levels, and inhibited the growth of PCa cell lines, human PCa explants, and tumor xenografts. Conclusions: CHKA can act as an AR chaperone, providing, to our knowledge, the first evidence for kinases as molecular chaperones, making CHKA both a marker of tumor progression and a potential therapeutic target for PCa. PMID:26657335

  6. Effects of choline chloride on electrodeposited Ni coating from a Watts-type bath

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yurong; Yang, Caihong; He, Jiawei; Wang, Wenchang [School of Petrochemical Engineering, Changzhou University, Changzhou 213164 (China); Mitsuzak, Naotoshi [Qualtec Co., Ltd, Osaka 590-0906 (Japan); Chen, Zhidong, E-mail: zdchen.lab@gmail.com [School of Material Science and Engineering, Jiangsu Key Laboratory of Materials, Surface and Technology, Changzhou University, Changzhou 213164 (China); Jiangsu Collaborative Innovation Center of Photovoltaic Science and Engineering, Changzhou University, Changzhou 213164 (China); Jiangsu Key Laboratory of Advanced Catalytic Material and Technology, Changzhou University, Changzhou 213164 (China)

    2016-05-30

    Graphical abstract: - Highlights: • ChCl was applied as additive and conducting salt in Watts-type bath. • Progressive addition of ChCl leads to the crystal orientation (1 1 1) predominant. • The grain size and microhardness were refined and enhanced by increasing ChCl. • ChCl could be a good alternative to NiCl{sub 2} and additives for bright Ni electroplating. - Abstract: Electrodeposition of bright nickel (Ni) was carried out in a Watts-type bath. Choline chloride (ChCl) was applied as a multifunctional additive and substitute for nickel chloride (NiCl{sub 2}) in a Watts-type bath. The function of ChCl was investigated through conductivity tests, anodic polarization, and cathodic polarization experiments. The studies revealed that ChCl performed well as a conducting salt, anodic activator, and cathodic inhibitor. The effects of ChCl on deposition rate, preferred orientation, grain size, surface morphology, and microhardness of Ni coatings were also studied. The deposition rate reached a maximum value of greater than 27 μm h{sup −1} when 20 g L{sup −1} ChCl was introduced to the bath. Using X-ray diffraction, it was confirmed that progressive addition of ChCl promoted the preferred crystal orientation modification from (2 0 0) and (2 2 0) to (1 1 1), refined grain size, and enhanced microhardness. The presence of ChCl lowered the roughness of the coating.

  7. Dietary choline during periadolescence attenuates cognitive damage caused by neonatal maternal separation in male rats.

    Science.gov (United States)

    Moreno Gudiño, Hayarelis; Carías Picón, Diamela; de Brugada Sauras, Isabel

    2017-07-01

    Choline (Ch) is an essential nutrient that acts as a cognitive facilitator when administered during perinatal periods, and it has been recognised as a 'pharmacological' agent that can ease cognitive dysfunctions provoked by exposure to damaging stimuli during early developmental stages. The aim of the present work is to determine whether providing a diet rich in Ch would reduce the severity of the memory deficit provoked by a neonatal stress episode in male adult rats. The effect of Ch on memory was measured using memory tasks such as object and place recognition. Ontogenetic manipulations were conducted during two sensitive developmental periods. During the first post-natal (PN) 14 days, only the male rat pups were selected and half of them were separated from the mother, group maternal separation (MS). Subsequently, during periadolescence (PN 21-60), the rats were exposed to a deficient (DEF = 0 g/kg Ch chloride), sufficient (CON = 1.1 g/kg Ch chloride), or supplemented (SUP = 5 g/kg Ch chloride) diets for this nutrient. The results indicated that for group MS, only rats fed with the SUP diet were able to recognise the familiar object and place that had been experienced 24 hours before, unlike groups DEF and CON. In addition, whereas rats in the non-separated group (No-MS) recognised the object independently of the diet, only rats that received a DEF diet failed to recognise the place, showing that a Ch deficit affects spatial memory tasks. These results show that Ch supplementation during periadolescence can attenuate the memory deficit provoked by extended neonatal stress.

  8. Prognostic value of choline and creatine in WHO grade II gliomas

    International Nuclear Information System (INIS)

    Hattingen, Elke; Zanella, Friedhelm E.; Pilatus, Ulrich; Raab, Peter; Franz, Kea; Setzer, Matthias; Gerlach, Ruediger; Lanfermann, Heiner

    2008-01-01

    The purpose of this study was to evaluate whether proton magnetic resonance spectroscopy ( 1 H-MRS) predicts survival time, tumor progression, and malignant transformation in patients with WHO grade II gliomas. 1 H-MRS and MR imaging (MRI) were performed before surgery in 45 patients with histologically proven WHO grade II gliomas. Metabolite concentrations of choline-containing compounds (Cho) and creatine/phosphocreatine (tCr) were normalized to contralateral brain tissue. Spectroscopic data as well as the extent of tumor resection, contrast enhancement, size and histopatholocical type of the tumor, age, sex, and first neurological symptoms of the patients were analyzed for survival, tumor progression, and malignant transformation for a follow-up period of 1 to 5 years. The normalized tCr of WHO grade II gliomas was a significant predictor for tumor progression (p=0.011) and for malignant tumor transformation (p=0.016). Further, contrast enhancement of the tumor (p=0.014) at the time of diagnosis was significant for malignant tumor transformation and extent of tumor resection for the tumor progression (p=0.007). All other parameters failed to predict any of the three endpoints. Normalized values of tCr in WHO grade II gliomas may have prognostic implications for this group of gliomas. As a rule of the thumb, low-grade gliomas with decreased tCr (relative tCr values below 1.0) may show longer progression-free times and later malignant transformation than low-grade gliomas with regular or increased tCr values. (orig.)

  9. Absolute choline concentration measured by quantitative proton MR spectroscopy correlates with cell density in meningioma

    Energy Technology Data Exchange (ETDEWEB)

    Yue, Qiang [University of Tsukuba, Department of Neurosurgery, Institute of Clinical Medicine, Tsukuba Science City, Ibaraki (Japan)]|[West China Hospital of Sichuan University, Huaxi MR Research Center, Department of Radiology, Chengdu (China); Shibata, Yasushi; Kawamura, Hiraku; Matsumura, Akira [University of Tsukuba, Department of Neurosurgery, Institute of Clinical Medicine, Tsukuba Science City, Ibaraki (Japan); Isobe, Tomonori [Kitasato University, Department of Medical Technology, School of Allied Health Sciences, Minato, Tokyo (Japan); Anno, Izumi [University of Tsukuba, Department of Radiology, Institute of Clinical Medicine, Tsukuba, Ibaraki (Japan); Gong, Qi-Yong [West China Hospital of Sichuan University, Huaxi MR Research Center, Department of Radiology, Chengdu (China)]|[University of Liverpool, Division of Medical Imaging, Faculty of Medicine, Liverpool (United Kingdom)

    2009-01-15

    This study was aimed to investigate the relationship between quantitative proton magnetic resonance spectroscopy (1H-MRS) and pathological changes in meningioma. Twenty-two meningioma cases underwent single voxel 1H-MRS (point-resolved spectroscopy sequence, repetition time/echo time = 2,000 ms/68, 136, 272 ms). Absolute choline (Cho) concentration was calculated using tissue water as the internal reference and corrected according to intra-voxel cystic/necrotic parts. Pathological specimens were stained with MIB-1 antibody to measure cell density and proliferation index. Correlation analysis was performed between absolute Cho concentration and cell density and MIB-1 labeled proliferation index. Average Cho concentration of all meningiomas before correction was 2.95 {+-} 0.86 mmol/kg wet weight. It was increased to 3.23 {+-} 1.15 mmol/kg wet weight after correction. Average cell density of all meningiomas was 333 {+-} 119 cells/HPF, and average proliferation index was 2.93 {+-} 5.72%. A linear, positive correlation between cell density and Cho concentration was observed (r = 0.650, P = 0.001). After correction of Cho concentration, the correlation became more significant (r = 0.737, P < 0.001). However, no significant correlation between Cho concentration and proliferation index was found. There seemed to be a positive correlation trend after correction of Cho concentration but did not reach significant level. Absolute Cho concentration, especially Cho concentration corrected according to intra-voxel cystic/necrotic parts, reflects cell density of meningioma. (orig.)

  10. Experimental study of vascularized nerve graft: evaluation of nerve regeneration using choline acetyltransferase activity.

    Science.gov (United States)

    Iwai, M; Tamai, S; Yajima, H; Kawanishi, K

    2001-01-01

    A comparative study of nerve regeneration was performed on vascularized nerve graft (VNG) and free nerve graft (FNG) in Fischer strain rats. A segment of the sciatic nerve with vascular pedicle of the femoral artery and vein was harvested from syngeneic donor rat for the VNG group and the sciatic nerve in the same length without vascular pedicle was harvested for the FNG group. They were transplanted to a nerve defect in the sciatic nerve of syngeneic recipient rats. At 2, 4, 6, 8, 12, 16, and 24 weeks after operation, the sciatic nerves were biopsied and processed for evaluation of choline acetyltransferase (CAT) activity, histological studies, and measurement of wet weight of the muscle innervated by the sciatic nerve. Electrophysiological evaluation of the grafted nerve was also performed before sacrifice. The average CAT activity in the distal to the distal suture site was 383 cpm in VNG and 361 cpm in FNG at 2 weeks; 6,189 cpm in VNG and 2,264 cpm in FNG at 4 weeks; and 11,299 cpm in VNG and 9,424 cpm in FNG at 6 weeks postoperatively. The value of the VNG group was statistically higher than that of the FNG group at 4 weeks postoperatively. Electrophysiological and histological findings also suggested that nerve regeneration in the VNG group was superior to that in the FNG group during the same period. However, there was no significant difference between the two groups after 6 weeks postoperatively in any of the evaluations. The CAT measurement was useful in the experiments, because it was highly sensitive and reproducible. Copyright 2001 Wiley-Liss, Inc.

  11. The substrate oxidation mechanism of pyranose 2-oxidase and other related enzymes in the glucose-methanol-choline superfamily.

    Science.gov (United States)

    Wongnate, Thanyaporn; Chaiyen, Pimchai

    2013-07-01

    Enzymes in the glucose-methanol-choline (GMC) oxidoreductase superfamily catalyze the oxidation of an alcohol moiety to the corresponding aldehyde. In this review, the current understanding of the sugar oxidation mechanism in the reaction of pyranose 2-oxidase (P2O) is highlighted and compared with that of other enzymes in the GMC family for which structural and mechanistic information is available, including glucose oxidase, choline oxidase, cholesterol oxidase, cellobiose dehydrogenase, aryl-alcohol oxidase, and pyridoxine 4-oxidase. Other enzymes in the family that have been newly discovered or for which less information is available are also discussed. A large primary kinetic isotope effect was observed for the flavin reduction when 2-d-D-glucose was used as a substrate, but no solvent kinetic isotope effect was detected for the flavin reduction step. The reaction of P2O is consistent with a hydride transfer mechanism in which there is stepwise formation of d-glucose alkoxide prior to the hydride transfer. Site-directed mutagenesis of P2O and pH-dependence studies indicated that His548 is a catalytic base that facilitates the deprotonation of C2-OH in D-glucose. This finding agrees with the current mechanistic model for aryl-alcohol oxidase, glucose oxidase, cellobiose dehydrogenase, methanol oxidase, and pyridoxine 4-oxidase, but is different from that of cholesterol oxidase and choline oxidase. Although all of the GMC enzymes share similar structural folding and use the hydride transfer mechanism for flavin reduction, they appear to have subtle differences in the fine-tuned details of how they catalyze substrate oxidation. © 2013 The Authors Journal compilation © 2013 FEBS.

  12. Specificity of choline metabolites for in vivo diagnosis of breast cancer using 1H MRS at 1.5 T

    International Nuclear Information System (INIS)

    Stanwell, Peter; Gluch, Laurence; Lean, Cynthia; Malycha, Peter; Mountford, Carolyn; Clark, David; Tomanek, Boguslaw; Baker, Luke; Giuffre, Bruno

    2005-01-01

    The purpose was to determine if in vivo proton magnetic resonance spectroscopy ( 1 H MRS) at 1.5 T can accurately provide the correct pathology of breast disease. Forty-three asymptomatic volunteers including three lactating mothers were examined and compared with 21 breast cancer patients. Examinations were undertaken at 1.5 T using a purpose-built transmit-receive single breast coil. Single voxel spectroscopy was undertaken using echo times of 135 and 350 ms. The broad composite resonance at 3.2 ppm, which includes contributions from choline, phosphocholine (PC), glycerophosphocholine (GPC), myo-inositol and taurine, was found not to be a unique marker for malignancy providing a diagnostic sensitivity and specificity of 80.0 and 86.0%, respectively. This was due to three of the asymptomatic volunteers and all of the lactating mothers also generating the broad composite resonance at 3.2 ppm. Optimised post-acquisitional processing of the spectra resolved a resonance at 3.22 ppm, consistent with PC, in patients with cancer. In contrast the spectra recorded for three false-positive volunteers, and the three lactating mothers had a resonance centred at 3.28 ppm (possibly taurine, myo-inositol or GPC). This improved the specificity of the test to 100%. Careful referencing of the spectra and post-acquisitional processing intended to optimise spectral resolution of in vivo MR proton spectra from human breast tissue resolves the composite choline resonance. This allows the distinction of patients with malignant disease from volunteers with a sensitivity of 80% and specificity of 100%. Therefore, resolution of the composite choline resonance into its constituent components improves the specificity of the in vivo 1 H MRS method, but does not overcome the problem of 20% false-negatives. (orig.)

  13. Choline kinase-alpha by regulating cell aggressiveness and drug sensitivity is a potential druggable target for ovarian cancer.

    Science.gov (United States)

    Granata, A; Nicoletti, R; Tinaglia, V; De Cecco, L; Pisanu, M E; Ricci, A; Podo, F; Canevari, S; Iorio, E; Bagnoli, M; Mezzanzanica, D

    2014-01-21

    Aberrant choline metabolism has been proposed as a novel cancer hallmark. We recently showed that epithelial ovarian cancer (EOC) possesses an altered MRS-choline profile, characterised by increased phosphocholine (PCho) content to which mainly contribute over-expression and activation of choline kinase-alpha (ChoK-alpha). To assess its biological relevance, ChoK-alpha expression was downmodulated by transient RNA interference in EOC in vitro models. Gene expression profiling by microarray analysis and functional analysis was performed to identify the pathway/functions perturbed in ChoK-alpha-silenced cells, then validated by in vitro experiments. In silenced cells, compared with control, we observed: (I) a significant reduction of both CHKA transcript and ChoK-alpha protein expression; (II) a dramatic, proportional drop in PCho content ranging from 60 to 71%, as revealed by (1)H-magnetic spectroscopy analysis; (III) a 35-36% of cell growth inhibition, with no evidences of apoptosis or modification of the main cellular survival signalling pathways; (IV) 476 differentially expressed genes, including genes related to lipid metabolism. Ingenuity pathway analysis identified cellular functions related to cell death and cellular proliferation and movement as the most perturbed. Accordingly, CHKA-silenced cells displayed a significant delay in wound repair, a reduced migration and invasion capability were also observed. Furthermore, although CHKA silencing did not directly induce cell death, a significant increase of sensitivity to platinum, paclitaxel and doxorubicin was observed even in a drug-resistant context. We showed for the first time in EOC that CHKA downregulation significantly decreased the aggressive EOC cell behaviour also affecting cells' sensitivity to drug treatment. These observations open the way to further analysis for ChoK-alpha validation as a new EOC therapeutic target to be used alone or in combination with conventional drugs.

  14. A modified choline-deficient, ethionine-supplemented diet reduces morbidity and retains a liver progenitor cell response in mice.

    Science.gov (United States)

    Passman, Adam M; Strauss, Robyn P; McSpadden, Sarah B; Finch-Edmondson, Megan L; Woo, Ken H; Diepeveen, Luke A; London, Roslyn; Callus, Bernard A; Yeoh, George C

    2015-12-01

    The choline-deficient, ethionine-supplemented (CDE) dietary model induces chronic liver damage, and stimulates liver progenitor cell (LPC)-mediated repair. Long-term CDE administration leads to hepatocellular carcinoma in rodents and lineage-tracing studies show that LPCs differentiate into functional hepatocytes in this model. The CDE diet was first modified for mice by our laboratory by separately administering choline-deficient chow and ethionine in the drinking water (CD+E diet). Although this CD+E diet is widely used, concerns with variability in weight loss, morbidity, mortality and LPC response have been raised by researchers who have adopted this model. We propose that these inconsistencies are due to differential consumption of chow and ethionine in the drinking water, and that incorporating ethionine in the choline-deficient chow, and altering the strength, will achieve better outcomes. Therefore, C57Bl/6 mice, 5 and 6 weeks of age, were fed an all-inclusive CDE diet of various strengths (67% to 100%) for 3 weeks. The LPC response was quantitated and cell lines were derived. We found that animal survival, LPC response and liver damage are correlated with CDE diet strength. The 67% and 75% CDE diet administered to mice older than 5 weeks and greater than 18 g provides a consistent and acceptable level of animal welfare and induces a substantial LPC response, permitting their isolation and establishment of cell lines. This study shows that an all-inclusive CDE diet for mice reproducibly induces an LPC response conducive to in vivo studies and isolation, whilst minimizing morbidity and mortality. © 2015. Published by The Company of Biologists Ltd.

  15. A modified choline-deficient, ethionine-supplemented diet reduces morbidity and retains a liver progenitor cell response in mice

    Directory of Open Access Journals (Sweden)

    Adam M. Passman

    2015-12-01

    Full Text Available The choline-deficient, ethionine-supplemented (CDE dietary model induces chronic liver damage, and stimulates liver progenitor cell (LPC-mediated repair. Long-term CDE administration leads to hepatocellular carcinoma in rodents and lineage-tracing studies show that LPCs differentiate into functional hepatocytes in this model. The CDE diet was first modified for mice by our laboratory by separately administering choline-deficient chow and ethionine in the drinking water (CD+E diet. Although this CD+E diet is widely used, concerns with variability in weight loss, morbidity, mortality and LPC response have been raised by researchers who have adopted this model. We propose that these inconsistencies are due to differential consumption of chow and ethionine in the drinking water, and that incorporating ethionine in the choline-deficient chow, and altering the strength, will achieve better outcomes. Therefore, C57Bl/6 mice, 5 and 6 weeks of age, were fed an all-inclusive CDE diet of various strengths (67% to 100% for 3 weeks. The LPC response was quantitated and cell lines were derived. We found that animal survival, LPC response and liver damage are correlated with CDE diet strength. The 67% and 75% CDE diet administered to mice older than 5 weeks and greater than 18 g provides a consistent and acceptable level of animal welfare and induces a substantial LPC response, permitting their isolation and establishment of cell lines. This study shows that an all-inclusive CDE diet for mice reproducibly induces an LPC response conducive to in vivo studies and isolation, whilst minimizing morbidity and mortality.

  16. The optimal timing to perform 18F/11C-choline PET/CT in patients with suspicion of relapse of prostate cancer: trigger PSA versus PSA velocity and PSA doubling time.

    Science.gov (United States)

    Calabria, Ferdinando; Rubello, Domenico; Schillaci, Orazio

    2014-12-09

    In the present short communication we considered the main publications focused on trigger prostate-specific antigen (PSA) and PSA kinetics that systematically compared 18F to 11C-choline PET/CT in order to establish the optimal time to perform choline PET/CT in relation to the trigger values and velocity, as well as doubling time of PSA serum levels.

  17. Flow injection determination of choline in milk hydrolysates by an immobilized enzyme reactor coupled to a selective hydrogen peroxide amperometric sensor

    Energy Technology Data Exchange (ETDEWEB)

    Pati, Sandra [Dipartimento di Chimica, Universita degli Studi di Bari, Via Orabona 4, 70126 Bari (Italy); Quinto, Maurizio [Dipartimento di Scienze Agroambientali, Chimica e Difesa Vegetale, Universita degli Studi di Foggia, Via Napoli 25, 71100 Foggia (Italy); Palmisano, Francesco [Dipartimento di Chimica, Universita degli Studi di Bari, Via Orabona 4, 70126 Bari (Italy)]. E-mail: palmisano@chimica.uniba.it

    2007-07-02

    A choline oxidase (ChO) immobilized enzyme reactor (IMER) prepared by glutaraldehyde coupling of the enzyme on aminopropyl modified controlled pore glass beads is described. The ChO-IMER was coupled, in a flow injection configuration system, to an interference free hydrogen peroxide amperometric sensor based on a Pt surface modified by an overoxidized polypyrrole film. The resulting analytical device responds selectively to choline and displays a sensitivity of 46.9 {+-} 0.2 {mu}C mM{sup -1} and a limit of detection, calculated at a signal-to-noise ratio equal to 3, of 7 {mu}M. Sensitivity remains constant for about 20 days and then starts to slowly deteriorate and after 2 months a 70% of the initial sensitivity was still retained. The application to choline determination in milk hydrolysates is demonstrated. Short- and long-term drift observed in the analytical response can be corrected by a bracketing technique.

  18. Genetic variants in the choline acetyltransferase (ChAT) gene are modestly associated with normal cognitive function in the elderly

    DEFF Research Database (Denmark)

    Mengel-From, J; Christensen, K; Thinggaard, M

    2011-01-01

    Genetic variants in the choline acetyltransferase (ChAT) gene have been suggested as risk factors for neurodegenerative Alzheimer's disease (AD). Here we tested the importance of genetic variants in the ChAT gene in normal cognitive function of elderly in a study sample of Danish twins...... and singletons (N = 2070). The ChAT rs3810950 A allele, which has been associated with increased risk for AD, was found to be associated with a decrease cognitive status evaluated by a five-component cognitive composite score [P = 0.03, regression coefficient -0.30, 95% confidence interval (CI) -0.57 to -0...

  19. {sup 11}C-Choline PET/CT in castration-resistant prostate cancer patients treated with docetaxel

    Energy Technology Data Exchange (ETDEWEB)

    Ceci, Francesco [University of Bologna, Service of Nuclear Medicine, S. Orsola-Malpighi Hospital, Bologna (Italy); Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola-Malpighi, UO Medicina Nucleare PAD. 30, Bologna (Italy); Castellucci, Paolo; Graziani, Tiziano; Renzi, Riccardo; Fanti, Stefano [University of Bologna, Service of Nuclear Medicine, S. Orsola-Malpighi Hospital, Bologna (Italy); Schiavina, Riccardo; Borghesi, Marco; Brunocilla, Eugenio [University of Bologna, Department of Urology, S. Orsola-Malpighi Hospital, Bologna (Italy); Di Tullio, Piergiorgio; Ardizzoni, Andrea [University of Bologna, Department of Oncology, S. Orsola-Malpighi Hospital, Bologna (Italy)

    2016-01-15

    To investigate the role of {sup 11}C-choline PET/CT for evaluating the response to treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel in comparison with PSA response. Inclusion criteria were (a) proven mCRPC, (b) docetaxel as first line of chemotherapy (docetaxel 75 mg/m{sup 2} + prednisone 5 mg), and (c) {sup 11}C-choline PET/CT and PSA values assessed before and after docetaxel administration. A total of 61 patients were retrospectively enrolled (mean age 68.9 years, range 57 - 84 years). {sup 11}C-Choline PET/CT was performed at baseline before docetaxel treatment (PET1) and after the end of treatment (PET2). PSA values were measured before treatment (PSA1) and after treatment (PSA2). PET2 was reported as complete response (CR), partial response (PR) or stable disease (SD). Progressive disease (PD) was considered if a new lesion was seen. PSA trend was calculated from the change in absolute values between PSA1 and PSA2. A decrease of ≥50 % between PSA1 and PSA2 was considered a PSA response. Clinical, radiological and laboratory follow-up ranged from 6 to 53 months (mean 13.5 months). Of the 61 patients, 40 (65.5 %) showed PD on PET2, 13 (21.3 %) showed SD, 2 (3.4 %) showed PR, and 6 (9.8 %) showed CR. An increasing PSA trend was seen in 29 patients (47.5 %) and a decreasing PSA trend in 32 patients (52.5 %). A PSA response of ≥50 % was seen in 25 patients (41 %). Radiological PD was seen in 23 of the 29 patients (79.3 %) with an increasing PSA trend, in 16 of the 32 patients (50 %) with a decreasing PSA trend, and in 11 of the 25 patients (44 %) with a PSA response of ≥50 %. In the multivariate statistical analysis, the presence of more than ten bone lesions detected on PET1 was significantly associated with an increased probability of PD on PET2. No association was observed between PSA level and PD on PET2. Our results suggest that an increasing PSA trend measured after docetaxel treatment could be

  20. Synthesis, molecular docking, DFT calculations and cytotoxicity activity of benzo[g]quinazoline derivatives in choline chloride-urea

    Science.gov (United States)

    Lakshmanan, Sivalingam; Govindaraj, Dharman; Ramalakshmi, Narayanan; Antony, S. Arul

    2017-12-01

    Green and highly efficient one-pot three component approach for the synthesis of benzo[g]quinazoline derivatives (6a-g) using Choline chloride-urea (DES). Synthesized compounds 6b and 6g showed the most potent biological activity against A549 lung cancer cell line. Docking simulation was performed to position compounds 6b and 6g showed the greater affinity for anaplastic lymphoma kinase (ALK) receptor. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity using DFT/6-31G level of theory.

  1. Crystallization and preliminary X-ray analysis of formate oxidase, an enzyme of the glucose–methanol–choline oxidoreductase family

    International Nuclear Information System (INIS)

    Maeda, Yoshifumi; Doubayashi, Daiju; Ootake, Takumi; Oki, Masaya; Mikami, Bunzo; Uchida, Hiroyuki

    2010-01-01

    Formate oxidase from A. oryzae RIB40 was crystallized and diffraction data were collected to a resolution of 2.4 Å. Formate oxidase (FOD), which catalyzes the oxidation of formate to yield carbon dioxide and hydrogen peroxide, belongs to the glucose–methanol–choline oxidoreductase (GMCO) family. FOD from Aspergillus oryzae RIB40, which has a modified FAD as a cofactor, was crystallized at 293 K by the hanging-drop vapour-diffusion method. The crystal was orthorhombic and belonged to space group C222 1 . Diffraction data were collected from a single crystal to 2.4 Å resolution

  2. PET/CT with 18F-choline: Physiological whole bio-distribution in male and female subjects and diagnostic pitfalls on 1000 prostate cancer patients: 18F-choline PET/CT bio-distribution and pitfalls. A southern Italian experience.

    Science.gov (United States)

    Calabria, Ferdinando; Chiaravalloti, Agostino; Cicciò, Carmelo; Gangemi, Vincenzo; Gullà, Domenico; Rocca, Federico; Gallo, Gianpasquale; Cascini, Giuseppe Lucio; Schillaci, Orazio

    2017-08-01

    The 11 C/ 18 F-choline is a PET/CT radiopharmaceutical useful in detecting tumors with high lipogenesis. 11 C/ 18 F-choline uptake can occur in physiological conditions or tumors. The knowledge of its bio-distribution is essential to recognize physiologic variants or diagnostic pitfalls. Moreover, few information are available on the bio-distribution of this tracer in female patients. Our aim was to discuss some documented 18 F-choline PET/CT pitfalls in prostate cancer patients. Our secondary aim was to describe the 18 F-choline bio-distribution in the female body. We collected diagnostic pitfalls in three PET centers examining 1000 prostate cancer by 18 F-choline PET/CT. All pitfalls were ensured by follow-up, imaging and/or histology. We also performed whole body 18 F-choline PET/CT in 5 female patients. 169/1000 (16.9%) patients showed pitfalls not owing to prostate cancer. These findings were due to inflammation, benign tumors while, in 1% of examined patients, a concomitant neoplasm was found. In the female body, the breast showed low physiological uptake. The accurate knowledge of 18 F-choline PET/CT bio-distribution and diagnostic pitfalls is essential. Correlative imaging and histological exam are often necessary to depict pitfalls. In women, the uptake in the breast is due to the physiological gradient of 18 F-choline uptake in the exocrine glands. Our results confirm the possibility of 18 F-choline uptake in several diseases other than prostate cancer. However, our experience was acquired on a large population and shows that a conspicuous amount of 18 F-choline diagnostic pitfalls are easily recognizable and attributable to inflammation. A new advance in knowledge is the minimal difference in terms of physiological tracer bio-distribution between male and female patients. The knowledge of the physiological bio-distribution and of the potential pitfalls linked of a tracer could help physicians to choose the best diagnostic and therapeutic approaches for a

  3. Variability of Gross Tumor Volume in Nasopharyngeal Carcinoma Using 11C-Choline and 18F-FDG PET/CT.

    Directory of Open Access Journals (Sweden)

    Jun Jiang

    Full Text Available This study was conducted to evaluate the variability of gross tumor volume (GTV using 11C-Choline and 18F-FDG PET/CT images for nasopharyngeal carcinomas boundary definition. Assessment consisted of inter-observer and inter-modality variation analysis. Four radiation oncologists were invited to manually contour GTV by using PET/CT fusion obtained from a cohort of 12 patients with nasopharyngeal carcinoma (NPC and who underwent both 11C-Choline and 18F-FDG scans. Student's paired-sample t-test was performed for analyzing inter-observer and inter-modality variability. Semi-automatic segmentation methods, including thresholding and region growing, were also validated against the manual contouring of the two types of PET images. We observed no significant variation in the results obtained by different oncologists in terms of the same type of PET/CT volumes. Choline fusion volumes were significantly larger than the FDG volumes (p < 0.0001, mean ± SD = 18.21 ± 8.19. While significantly consistent results were obtained between the oncologists and the standard references in Choline volumes compared with those in FDG volumes (p = 0.0025. Simple semi-automatic delineation methods indicated that 11C-Choline PET images could provide better results than FDG volumes (p = 0.076, CI = [-0.29, 0.025]. 11C-Choline PET/CT may be more advantageous in GTV delineation for the radiotherapy of NPC than 18F-FDG. Phantom simulations and clinical trials should be conducted to prove the possible improvement of the treatment outcome.

  4. Role of Choline-Docosahexaenoic acid and Trigonella foenum graecum Seed Extract on Ovariectomy Induced Dyslipidemia and Oxidative Stress in Rat Model

    Directory of Open Access Journals (Sweden)

    Nagamma Takkella

    2018-01-01

    Full Text Available Background: Menopause is characterized by the deficiency of ovarian hormones, mainly estrogen. The decline in estrogen hormone is contributing the cardiovascular disorders in women. Hormone replacement therapy has disadvantages especially a higher risk of breast, ovarian and endometrial cancers upon chronic use. Phytoestrogens may be used as an alternative to hormone replacement therapy. Aim and Objectives: This study was designed to scientifically evaluate the role of Choline- Docosahexaenoic Acid (DHA and Trigonella foenum graecum (TFG seed extract on Ovariectomy (OVX induced dyslipidemia and oxidative stress in rat model. Material and Methods: Female Wistar rats were allocated into four groups (n=6:1 Sham control, 2 ovariectomized, 3 ovariectomized+ choline-DHA and 4 ovariectomized + choline-DHA+TFG. After 30 days of treatment, fasting blood samples and liver tissues were collected. Serum was analyzed for lipid profile and liver homogenates were used for assessment of oxidative stress and antioxidant activity. Results: Ovariectomized rats showed significantly increased (P<0.05 Total Cholesterol (TC, Low Density Lipoprotein (LDL levels and decreased High Density Lipoprotein (HDL levels. Treating ovariectomized rats with choline-DHA and TFG seed extract significantly lowered (P<0.05 total cholesterol, LDL and markedly increased the HDL. Significantly increased (P≤0.01 Thiobarbituric Acid Reactive Substances (TBARS and reduced (P<0.05 glutathione levels were observed in OVX group. The synergetic effect of choline-DHA and fenugreek showed a significant reduction ((P≤0.01 in TBARS levels. Conclusion: These results showed that choline-DHA with TFG supplementation have a favorable effect on OVX induced hyperlipidemia and oxidative stress. Therefore, these components may be a therapeutic agent for treating the menopause induced hyperlipidemia or oxidative stress.

  5. Escherichia coli O157:H7 Converts Plant-Derived Choline to Glycine Betaine for Osmoprotection during Pre- and Post-harvest Colonization of Injured Lettuce Leaves

    Directory of Open Access Journals (Sweden)

    Russell A. Scott

    2017-12-01

    Full Text Available Plant injury is inherent to the production and processing of fruit and vegetables. The opportunistic colonization of damaged plant tissue by human enteric pathogens may contribute to the occurrence of outbreaks of foodborne illness linked to produce. Escherichia coli O157:H7 (EcO157 responds to physicochemical stresses in cut lettuce and lettuce lysates by upregulation of several stress response pathways. We investigated the tolerance of EcO157 to osmotic stress imposed by the leakage of osmolytes from injured lettuce leaf tissue. LC-MS analysis of bacterial osmoprotectants in lettuce leaf lysates and wound washes indicated an abundant natural pool of choline, but sparse quantities of glycine betaine and proline. Glycine betaine was a more effective osmoprotectant than choline in EcO157 under osmotic stress conditions in vitro. An EcO157 mutant with a deletion of the betTIBA genes, which are required for biosynthesis of glycine betaine from imported choline, achieved population sizes twofold lower than those of the parental strain (P < 0.05 over the first hour of colonization of cut lettuce in modified atmosphere packaging (MAP. The cell concentrations of the betTIBA mutant also were 12-fold lower than those of the parental strain (P < 0.01 when grown in hypertonic lettuce lysate, indicating that lettuce leaf cellular contents provide choline for osmoprotection of EcO157. To demonstrate the utilization of available choline by EcO157 for osmoadaptation in injured leaf tissue, deuterated (D-9 choline was introduced to wound sites in MAP lettuce; LC-MS analysis revealed the conversion of D9-choline to D-9 glycine betaine in the parental strain, but no significant amounts were observed in the betTIBA mutant. The EcO157 ΔbetTIBA-ΔotsBA double mutant, which is additionally deficient in de novo synthesis of the compatible solute trehalose, was significantly less fit than the parental strain after their co-inoculation onto injured lettuce leaves and

  6. Evaluation of 11C-choline PET/CT for primary diagnosis and staging of urothelial carcinoma of the upper urinary tract: a pilot study

    International Nuclear Information System (INIS)

    Sassa, Naoto; Yamamoto, Tokunori; Gotoh, Momokazu; Kato, Katsuhiko; Ikeda, Mitsuru; Shimamoto, Kazuhiro; Yamamoto, Seiichi; Abe, Shinji; Iwano, Shingo; Ito, Shinji; Naganawa, Shinji

    2014-01-01

    We conducted a pilot study to prospectively evaluate the efficacy of PET/CT with 11 C-choline (choline PET/CT) for primary diagnosis and staging of urothelial carcinoma of the upper urinary tract (UUT-UC). Enrolled in this study were 16 patients (9 men, 7 women; age range 51 - 83 years, mean ± SD 69 ± 10.8 years) with suspected UUT-UC. The patients were examined by choline PET/CT, and 13 underwent laparoscopic nephroureterectomy and partial cystectomy. Lymphadenectomy and chemotherapy were also performed as necessary in some of the patients. Of the 16 patients, 12 were confirmed to have UUT-UC (7 renal pelvis carcinoma and 5 ureteral carcinoma), 1 had malignant lymphoma (ureter), 1 had IgG4-related disease (ureter), and 2 had other benign diseases (ureter). Of the 16 study patients, 13 showed definite choline uptake in urothelial lesions, and of these, 11 had UUT-UC, 1 had malignant lymphoma, and 1 had IgG4-related disease. Three patients without choline uptake comprised one with UUT-UC and two with benign diseases. Of the 12 patients with UUT-UC, 3 had distant metastases, 2 had metastases only in the regional lymph nodes, and 7 had no metastases. Distant metastases and metastases in the regional lymph nodes showed definite choline uptake. The outcome in patients with UUT-UC, which was evaluated 592 - 1,530 days after surgery, corresponded to the patient classification based on the presence or absence of metastases and locoregional or distant metastases. Choline uptake determined as SUVmax 10 min after administration was significantly higher than at 20 min in metastatic tumours of UUT-UC (p < 0.05), whereas there was no statistically significant difference between the SUVmax values at 10 and those at 20 min in primary tumours of UUT-UC. This study suggests that choline PET/CT is a promising tool for the primary diagnosis and staging of UUT-UC. (orig.)

  7. Distinct choline metabolic profiles are associated with differences in gene expression for basal-like and luminal-like breast cancer xenograft models

    International Nuclear Information System (INIS)

    Moestue, Siver A; Borgan, Eldrid; Huuse, Else M; Lindholm, Evita M; Sitter, Beathe; Børresen-Dale, Anne-Lise; Engebraaten, Olav; Mælandsmo, Gunhild M; Gribbestad, Ingrid S

    2010-01-01

    Increased concentrations of choline-containing compounds are frequently observed in breast carcinomas, and may serve as biomarkers for both diagnostic and treatment monitoring purposes. However, underlying mechanisms for the abnormal choline metabolism are poorly understood. The concentrations of choline-derived metabolites were determined in xenografted primary human breast carcinomas, representing basal-like and luminal-like subtypes. Quantification of metabolites in fresh frozen tissue was performed using high-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). The expression of genes involved in phosphatidylcholine (PtdCho) metabolism was retrieved from whole genome expression microarray analyses. The metabolite profiles from xenografts were compared with profiles from human breast cancer, sampled from patients with estrogen/progesterone receptor positive (ER+/PgR+) or triple negative (ER-/PgR-/HER2-) breast cancer. In basal-like xenografts, glycerophosphocholine (GPC) concentrations were higher than phosphocholine (PCho) concentrations, whereas this pattern was reversed in luminal-like xenografts. These differences may be explained by lower choline kinase (CHKA, CHKB) expression as well as higher PtdCho degradation mediated by higher expression of phospholipase A2 group 4A (PLA2G4A) and phospholipase B1 (PLB1) in the basal-like model. The glycine concentration was higher in the basal-like model. Although glycine could be derived from energy metabolism pathways, the gene expression data suggested a metabolic shift from PtdCho synthesis to glycine formation in basal-like xenografts. In agreement with results from the xenograft models, tissue samples from triple negative breast carcinomas had higher GPC/PCho ratio than samples from ER+/PgR+ carcinomas, suggesting that the choline metabolism in the experimental models is representative for luminal-like and basal-like human breast cancer. The differences in choline metabolite

  8. Incidental detection of colorectal cancer via 1(8)F-choline PET/CT in a patient with recurrent prostate cancer: usefulness of early images.

    Science.gov (United States)

    Bagni, Oreste; Filippi, Luca; Schillaci, Orazio

    2015-06-01

    A 74-year-old man with history of prostate cancer underwent F-choline PET/CT for restaging. Early acquisition of the pelvic region revealed intense uptake in prostate, with infiltration of the posterior wall of the bladder. Furthermore, focal uptake in the thickened anterior wall of the rectum was detected. Whole-body scan at 60 minutes confirmed early findings in pelvis, although the infiltration of the bladder was no more evident due to interference of radioactive urine. Biopsy demonstrated the presence of colorectal carcinoma. The dual-phase protocol resulted in significant clinical impact to clearly characterize focuses of abnormal F-choline uptake in the pelvic region.

  9. Metabolic pathways promoting intrahepatic fatty acid accumulation in methionine and choline deficiency: implications for the pathogenesis of steatohepatitis.

    Science.gov (United States)

    Macfarlane, David P; Zou, Xiantong; Andrew, Ruth; Morton, Nicholas M; Livingstone, Dawn E W; Aucott, Rebecca L; Nyirenda, Moffat J; Iredale, John P; Walker, Brian R

    2011-02-01

    The pathological mechanisms that distinguish simple steatosis from steatohepatitis (or NASH, with consequent risk of cirrhosis and hepatocellular cancer) remain incompletely defined. Whereas both a methionine- and choline-deficient diet (MCDD) and a choline-deficient diet (CDD) lead to hepatic triglyceride accumulation, MCDD alone is associated with hepatic insulin resistance and inflammation (steatohepatitis). We used metabolic tracer techniques, including stable isotope ([¹³C₄]palmitate) dilution and mass isotopomer distribution analysis (MIDA) of [¹³C₂]acetate, to define differences in intrahepatic fatty acid metabolism that could explain the contrasting effect of MCDD and CDD on NASH in C57Bl6 mice. Compared with control-supplemented (CS) diet, liver triglyceride pool sizes were similarly elevated in CDD and MCDD groups (24.37 ± 2.4, 45.94 ± 3.9, and 43.30 ± 3.5 μmol/liver for CS, CDD, and MCDD, respectively), but intrahepatic neutrophil infiltration and plasma alanine aminotransferase (31 ± 3, 48 ± 4, 231 ± 79 U/l, P triglyceride pool differed between groups. Unlike CDD, MCDD had a defect in hepatic triglyceride export that was confirmed using intravenous tyloxapol (142 ± 21, 122 ± 15, and 80 ± 7 mg·kg⁻¹·h⁻¹, P metabolism may promote the development of steatohepatitis. Similar mechanisms may predispose to hepatocyte damage in human NASH.

  10. Carbon-11 choline or FDG-PET for staging of oesophageal cancer?

    International Nuclear Information System (INIS)

    Jager, P.L.; Que, T.H.; Vaalburg, W.; Pruim, J.; Elsinga, P.; Plukker, J.T.

    2001-01-01

    We investigated the feasibility of using carbon-11 choline (CHOL) positron emission tomography (PET) for the staging of oesophageal cancer, in comparison with fluorine-18 fluorodeoxyglucose (FDG) PET, using histopathological findings as the gold standard. Eighteen patients were studied: 16 patients with cancer of the oesophagus or gastro-oesophageal junction and two with in situ carcinoma/high-grade dysplasia. PET imaging was performed 5 min (CHOL) or 90 min (FDG) after injection of 370 MBq of the tracer. PET images were analysed by two independent and blinded physicians using visual and standardised uptake value (SUV) analysis. PET results were compared with surgical and histopathological findings. FDG-PET was able to detect all (100%) of the 16 malignant primary lesions, while CHOL-PET detected 73%. In situ carcinoma (n=1) and high-grade dysplasia (n=1) were not visualised with either tracer. Diffuse uptake of the tracers was noted in areas of Barrett's oesophagitis. Twelve patients had locoregional metastases (N1) that were not detected with either FDG or CHOL. Six patients had additional distant nodal (M1a) metastases; four of six (66%) were visualised by FDG, and three of five (60%) by CHOL-PET. On a lesion basis, FDG-PET detected 10/12 non-regional metastases (sensitivity 83%), while CHOL-PET detected 5/12 (sensitivity 42%). Haematogenous distant metastases (M1b) were positive on FDG-PET in three of four patients, and on CHOL-PET in two of four. SUV values were significantly higher for FDG (FDG 6.6±3.5, CHOL 5.5±2.5, P=0.04). CHOL-PET is able to visualise oesophageal carcinoma and its metastases, but appears to be inferior to FDG-PET. Presumably this is the result of lower tumoural uptake and considerable non-specific uptake of CHOL in liver, stomach wall, pancreas and small intestine. Further studies are needed to confirm these data. (orig.)

  11. Carbon-11 choline or FDG-PET for staging of oesophageal cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Jager, P.L.; Que, T.H.; Vaalburg, W.; Pruim, J.; Elsinga, P. [PET Centre, Groningen Univ. Hospital (Netherlands); Plukker, J.T. [Dept. of Surgical Oncology, Groningen University Hospital (Netherlands)

    2001-12-01

    We investigated the feasibility of using carbon-11 choline (CHOL) positron emission tomography (PET) for the staging of oesophageal cancer, in comparison with fluorine-18 fluorodeoxyglucose (FDG) PET, using histopathological findings as the gold standard. Eighteen patients were studied: 16 patients with cancer of the oesophagus or gastro-oesophageal junction and two with in situ carcinoma/high-grade dysplasia. PET imaging was performed 5 min (CHOL) or 90 min (FDG) after injection of 370 MBq of the tracer. PET images were analysed by two independent and blinded physicians using visual and standardised uptake value (SUV) analysis. PET results were compared with surgical and histopathological findings. FDG-PET was able to detect all (100%) of the 16 malignant primary lesions, while CHOL-PET detected 73%. In situ carcinoma (n=1) and high-grade dysplasia (n=1) were not visualised with either tracer. Diffuse uptake of the tracers was noted in areas of Barrett's oesophagitis. Twelve patients had locoregional metastases (N1) that were not detected with either FDG or CHOL. Six patients had additional distant nodal (M1a) metastases; four of six (66%) were visualised by FDG, and three of five (60%) by CHOL-PET. On a lesion basis, FDG-PET detected 10/12 non-regional metastases (sensitivity 83%), while CHOL-PET detected 5/12 (sensitivity 42%). Haematogenous distant metastases (M1b) were positive on FDG-PET in three of four patients, and on CHOL-PET in two of four. SUV values were significantly higher for FDG (FDG 6.6{+-}3.5, CHOL 5.5{+-}2.5, P=0.04). CHOL-PET is able to visualise oesophageal carcinoma and its metastases, but appears to be inferior to FDG-PET. Presumably this is the result of lower tumoural uptake and considerable non-specific uptake of CHOL in liver, stomach wall, pancreas and small intestine. Further studies are needed to confirm these data. (orig.)

  12. Visualisation of bladder cancer using 11C-choline PET: first clinical experience

    International Nuclear Information System (INIS)

    De Jong, Igle J.; Pruim, Jan; Elsinga, Philip H.; Jongen, Maud M.G.J.; Vaalburg, Willem; Mensink, Han J.A.

    2002-01-01

    Fluorine-18 fluorodeoxyglucose (FDG), the most widely used radiopharmaceutical in positron emission tomography (PET) for oncological purposes, is unsuitable for imaging of bladder cancer owing to high excretion into the urine. More specific PET radiopharmaceuticals which are not excreted into urine would be welcome. Carbon-11 labelled choline (CHOL) is a new radiopharmaceutical potentially useful for tumour imaging and is not excreted into the urine. We prospectively studied the visualisation of bladder cancer using CHOL PET. Eighteen patients with bladder cancer and five healthy volunteers were included. Bladder cancer was first diagnosed by transurethral resection or by biopsy of the tumour. Next, PET images were performed before surgical treatment by cystectomy. The histopathological findings after cystectomy were used as the gold standard. PET images were performed on either an ECAT 951/31 or an ECAT Exact HR+ system. Attenuation-corrected PET images were obtained after injection of 400 MBq CHOL. PET images were analysed by two independent physicians using visual analysis and calculation of the standardised uptake value (SUV). In the normal bladder wall, the uptake of CHOL was low, and the bladder margin was only outlined by minimal urinary radioactivity, if present. In ten patients the tumour was detected correctly by CHOL PET, with an SUV of 4.7±3.6 (mean±SD). One false positive CHOL PET scan was seen in a patient with an indwelling catheter for 2 weeks prior to the PET scan. In two patients, lymph node metastases were detected by CHOL PET. A micrometastasis <5 mm was not visualised with CHOL PET. In seven patients, no residual tumour was found after surgery. In six of seven patients CHOL PET imaging was negative. In situ carcinoma, dysplasia and a non-invasive urothelial tumour (pTa) remained undetected in three of these six patients. Minimal to no urinary tract radioactivity was seen in 22/23 subjects. Non-specific uptake of CHOL was observed in the small

  13. Change of choline compounds in sodium selenite-induced apoptosis of rats used as quantitative analysis by in vitro 9.4T MR spectroscopy

    DEFF Research Database (Denmark)

    Cao, Zhen; Wu, Lin-Ping; Li, Yun-Xia

    2008-01-01

    staining was employed to detect and confirm the change of liver cells. RESULTS: Good (1)H-MR spectra of perchloric acid extract from liver tissue of rats were obtained. The conventional metabolites were detected and assigned. Concentrations of different ingredient choline compounds in treatment group vs...

  14. Amyloid Beta Peptide 1-40 and the Function of Rat Hippocampal Hemicholinium-3 Sensitive Choline Carriers: Effects of a Proteolytic Degradation in Vitro

    Czech Academy of Sciences Publication Activity Database

    Krištofíková, Z.; Tejkalová, H.; Klaschka, Jan

    2001-01-01

    Roč. 26, č. 3 (2001), s. 203-212 ISSN 0364-3190 R&D Projects: GA MZd IZ3702 Institutional research plan: AV0Z1030915 Keywords : abeta * bromelain * papain * choline uptake * hemicholinium-3 * rat hippocampus Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 1.638, year: 2001

  15. Targeting personalized medicine in a non-Hodgkin lymphoma patient with {sup 18F}-FDG and {sup 18F}-choline PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Thalles H.; Filho, Raul S.; Castro, Ana Carolina G.; Paulino Junior, Eduardo; Mamede, Marcelo, E-mail: mamede.mm@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

    2017-02-15

    Early diagnosis and staging of non-Hodgkin lymphoma (NHL) is essential for therapeutic strategy decision. Positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose (FDG), a glucose analogue, labeled with fluor-18 ({sup 18F}-FDG) has been used to evaluate staging, therapy response and prognosis in NHL patients. However, in some cases, {sup 18F}-FDG has shown false- -positive uptake due to inflammatory reaction after chemo and/or radiation therapy. In this case report, we present a NHL patient evaluated with {sup 18F}-FDG and {sup 18F}-choline PET/CT scan imaging pre- and post-therapy. {sup 18F}-FDG and {sup 18F}-choline PET/CT were performed for the purpose of tumor staging and have shown intense uptake in infiltrative tissue as well as in the lymph node, but with some mismatching in the tumor. Post-treatment {sup 18F}-FDG and {sup 18F}-choline PET/ CT scans revealed no signs of radiotracer uptake, suggesting complete remission of the tumor. {sup 18F}-choline may be a complimentary tool for staging and assessment of therapeutic response in non-Hodgkin lymphoma, while non-{sup 18F}-FDG tracer can be used for targeted therapy and patient management. (author)

  16. Methyl group balance in brain and liver: role of choline on increased S-adenosyl methionine (SAM) demand by chronic arsenic exposure.

    Science.gov (United States)

    Ríos, Rosalva; Santoyo, Martha E; Cruz, Daniela; Delgado, Juan Manuel; Zarazúa, Sergio; Jiménez-Capdeville, María E

    2012-11-30

    Arsenic toxicity has been related to its interference with one carbon metabolism, where a high demand of S-adenosylmethionine (SAM) for arsenic methylation as well as a failure of its regeneration would compromise the availability of methyl groups for diverse cellular functions. Since exposed animals show disturbances of methylated products such as methylated arginines, myelin and axon membranes, this work investigates whether alterations of SAM, choline and phosphatidylcholine (PC) in the brain of arsenic exposed rats are associated with myelin alterations and myelin basic protein (MBP) immunoreactivity. Also these metabolites, morphologic and biochemical markers of methyl group alterations were analyzed in the liver, the main site of arsenic methylation. In adult, life-long arsenic exposed rats through drinking water (3 ppm), no changes of SAM, choline and PC concentrations where found in the brain, but SAM and PC were severely decreased in liver accompanied by a significant increase of choline. These results suggest that choline plays an important role as methyl donor in arsenic exposure, which could underlie hepatic affections observed when arsenic exposure is combined with other environmental factors. Also, important myelin and nerve fiber alterations, accompanied by a 75% decrease of MBP immunoreactivity were not associated with a SAM deficit in the brain. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. A 24-hour dietary recall for assessing the intake pattern of choline among Bangladeshi pregnant women at their third trimester of pregnancy

    Directory of Open Access Journals (Sweden)

    Shatabdi Goon

    2014-04-01

    Full Text Available Maternal choline intake during the third trimester of human pregnancy can modify systemic and local epigenetic marks in fetal-derived tissues, promoting better pregnancy outcomes, increased immunity, as well as improved mental and physical work capacity with proper memory and cognitive development. 103 pregnant women presenting to the antenatal care of Azimpur Maternity Hospital of Dhaka, Bangladesh in their third trimester of pregnancy were randomly selected for this cross sectional study exploring dietary intake patterns of choline. A dietary recall form was administered to estimate frequency and amount of food consumption of foods for the previous 24 hours. Most women reported diets that delivered less than the recommended choline intake (mean ± SD; 189.5 ± 98.2 providing only 42.72% of total RDA value. The results of this study may indicate that dietary choline among pregnant, Bangladeshi women may not be adequate to meet the needs of both, the mother and fetus. Further studies are warranted to determine clinical implications. Normal 0 false false false MicrosoftInternetExplorer4

  18. Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome

    NARCIS (Netherlands)

    Smits, L.P.; Kootte, R.S.; Levin, E.; Prodan, A.; Fuentes, S.; Zoetendal, E.G.; Wang, Z; Levison, B.S.; Cleophas, M.C.P.; Kemper, E.M.; Dallinga-Thie, G.M.; Groen, A.K.; Joosten, L.A.B.; Netea, M.G.; Stroes, E.S.; Vos, W.M. de; Hazen, S.L.; Nieuwdorp, M.

    2018-01-01

    BACKGROUND: Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly

  19. Effect of vegan fecal microbiota transplantation on carnitine- and choline-derived trimethylamine-N-oxide production and vascular inflammation in patients with metabolic syndrome

    NARCIS (Netherlands)

    Smits, Loek P.; Kootte, Ruud S.; Levin, Evgeni; Prodan, Andrei; Fuentes, Susana; Zoetendal, Erwin G.; Wang, Zeneng; Levison, Bruce S.; Cleophas, Maartje C.P.; Kemper, E.M.; Dallinga-Thie, Geesje M.; Groen, Albert K.; Joosten, Leo A.B.; Netea, Mihai G.; Stroes, Erik S.G.; Vos, de Willem M.; Hazen, Stanley L.; Nieuwdorp, Max

    2018-01-01

    Background--Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly

  20. Effect of dietary γ-aminobutyric acid on the nerve growth factor and the choline acetyltransferase in the cerebral cortex and hippocampus of ovariectomized female rats.

    Science.gov (United States)

    Tujioka, Kazuyo; Thanapreedawat, Panicha; Yamada, Takashi; Yokogoshi, Hidehiko; Horie, Kenji; Kim, Mujo; Tsutsui, Kazumi; Hayase, Kazutoshi

    2014-01-01

    The brain protein synthesis and the plasma concentration of growth hormone (GH) is sensitive to the dietary γ-aminobutyric acid (GABA) in ovariectomized female rats; however, the role of dietary GABA on biomarkers including nerve growth factor (NGF) and choline acetyltransferase for the function of cholinergic neurons remains unknown in ovariectomized female rats. The purpose of this study was to determine whether the dietary GABA affects the concentration and mRNA level of NGF, and the activity of choline acetyltransferase in the brains of ovariectomized female rats. Experiments were done on two groups of 24-wk-old ovariectomized female rats given 0 or 0.5% GABA added to a 20% casein diet. The concentrations of NGF and activities of choline acetyltransferase in the cerebral cortex and hippocampus, and mRNA level of NGF in the hippocampus increased significantly with the 20% casein+0.5% GABA compared with the 20% casein diet alone. In the hippocampus, the mRNA level of NGF significantly correlated with the NGF concentration (r=0.714, pGABA to ovariectomized female rats is likely to control the mRNA level and concentration of NGF and cause an increase in the activity of choline acetyltransferase in the brains.

  1. Impact of total PSA, PSA doubling time and PSA velocity on detection rates of 11C-Choline positron emission tomography in recurrent prostate cancer

    NARCIS (Netherlands)

    Rybalov, Maxim; Breeuwsma, Anthonius J.; Leliveld, Anna M.; Pruim, Jan; Dierckx, Rudi A.; de Jong, Igle J.

    PURPOSE: To evaluate the effect of total PSA (tPSA) and PSA kinetics on the detection rates of (11)C-Choline PET in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) or external beam radiotherapy (EBRT). METHODS: We included 185 patients with BCR after RP (PSA >0.2 ng/ml)

  2. Organic cation transporter 2 (SLC22A2), a low-affinity and high-capacity choline transporter, is preferentially enriched on synaptic vesicles in cholinergic neurons.

    Science.gov (United States)

    Nakata, T; Matsui, T; Kobayashi, K; Kobayashi, Y; Anzai, N

    2013-11-12

    Organic cation transporters (OCTs) are expressed mainly in the kidney and liver. OCTs transport intrinsic organic cations, including monoamine, dopamine, serotonine and choline, across the plasma membrane. Here, we demonstrate that OCT2 (SLC22A2) is expressed in cholinergic neurons, motoneurons in the anterior horn of the spinal cord, and is implicated in acetylcholine (Ach) recycling in presynaptic terminals. Application of rabbit anti-peptide antibody revealed that OCT2 was expressed in the anterior horn of the spinal cord. Double immunostaining of muscle sections with anti-OCT2 and alpha-bungarotoxin (BTX) revealed that OCT2 was localized in the neuromuscular junctions (NMJs). Immunoelectron microscopy revealed that OCT2 was localized both in synaptic vesicles (SVs) in presynaptic terminals around the motoneurons (C-terminals) and in SVs in nerve terminals in NMJs. The similarity in the distribution of OCT2 in cholinergic neurons and that of vesicular acetyl choline transporter (VAchT), and the fact that OCT2 can transport choline suggest that OCT2 could work as a low-affinity and high-capacity choline transporter at presynaptic terminals in cholinergic neurons in a firing-dependent manner. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Folate, vitamin B12, alpha-tocopherol and selected liver components in periparturient dairy goats supplemented with choline and vitamin E

    Directory of Open Access Journals (Sweden)

    V. Dell'Orto

    2010-04-01

    Full Text Available The influence of rumen-protected choline and vitamin E administration on status of folate, vitamin B12, and vitamin E and selected liver components was studied on 4 groups of 12 periparturient dairy goats: control, CTR; choline supplemented, RPC; vitamin E, VITE; choline and vitamin E, RPCE. Plasma folate did not differ between groups, except at parturition when RPC and RPCE goats had higher folate levels than CTR and VITE animals. Neither RPC nor vitamin E affected vitamin B12 plasma concentrations, while a time effect was observed after the third week of lactation, when B12 levels in each group started to increase. Alpha-tocopherol supplementation was associated with increased plasma a-tocopherol in the VITE and RPCE compared to the CRT and RPC groups, while RPC supplementation did not affect a-tocopherol levels in both RPC and RPCE groups compared to CTR and VITE ones. In control and RPC goats liver total lipid did not differ, while DNA contents and their ratio, were respectively higher and lower in RPC supplemented animals. Overall these results suggest that greater choline availability seems to be essential for optimising metabolic health and methyl group status, in dairy ruminants.

  4. The concentration of N-acetyl aspartate, creatine + phosphocreatine, and choline in different parts of the brain in adulthood and senium

    DEFF Research Database (Denmark)

    Christiansen, P; Toft, P; Larsson, H B

    1993-01-01

    The fully relaxed water signal was used as an internal standard in a STEAM experiment to calculate the concentrations of the metabolites: N-acetyl aspartate (NAA), creatine + phosphocreatine (Cr + PCr), and choline (Cho) containing compounds in four different parts of the brain in two age groups...

  5. Intensity Modulated Radiation Therapy Dose Painting for Localized Prostate Cancer Using 11C-choline Positron Emission Tomography Scans

    International Nuclear Information System (INIS)

    Chang, Joe H.; Lim Joon, Daryl; Lee, Sze Ting; Gong, Sylvia J.; Anderson, Nigel J.; Scott, Andrew M.; Davis, Ian D.; Clouston, David; Bolton, Damien; Hamilton, Christopher S.; Khoo, Vincent

    2012-01-01

    Purpose: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using 11 C-choline positron emission tomography PET scans in patients with localized prostate cancer. Methods and Materials: This was an RT planning study of 8 patients with prostate cancer who had 11 C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV 60% and SUV 70% ). Three IMRT plans were generated for each patient: PLAN 78 , which consisted of whole-prostate radiation therapy to 78 Gy; PLAN 78-90 , which consisted of whole-prostate RT to 78 Gy, a boost to the SUV 60% to 84 Gy, and a further boost to the SUV 70% to 90 Gy; and PLAN 72-90 , which consisted of whole-prostate RT to 72 Gy, a boost to the SUV 60% to 84 Gy, and a further boost to the SUV 70% to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP PET ) and on prostatectomy-defined volumes (TCP path ), and rectal normal tissue complication probabilities (NTCP) were compared between the plans. Results: All plans for all patients reached prescription doses while adhering to dose constraints. TCP PET values for PLAN 78 , PLAN 78-90 , and PLAN 72-90 were 65%, 97%, and 96%, respectively. TCP path values were 71%, 97%, and 89%, respectively. Both PLAN 78-90 and PLAN 72-90 had significantly higher TCP PET (P=.002 and .001) and TCP path (P 78 . PLAN 78-90 and PLAN 72-90 were not significantly different in terms of TCP PET or TCP path . There were no significant differences in rectal NTCPs between the 3 plans. Conclusions: IMRT dose painting for localized prostate cancer using 11 C-choline PET scans is technically feasible. Dose painting results in higher TCPs without higher NTCPs.

  6. Diagnostic performance of 11C-choline PET/CT and bone scintigraphy in the detection of bone metastases in patients with prostate cancer.

    Science.gov (United States)

    Kitajima, Kazuhiro; Fukushima, Kazuhito; Yamamoto, Shingo; Kato, Takashi; Odawara, Soichi; Takaki, Haruyuki; Fujiwara, Masayuki; Yamakado, Koichiro; Nakanishi, Yukako; Kanematsu, Akihiro; Nojima, Michio; Hirota, Shozo

    2017-08-01

    The aim of this study was to compare 11C-choline PET/CT and bone scintigraphy (BS) for detection of bone metastases in patients with prostate cancer. Twenty-one patients with histologically proven prostate cancer underwent 11C-choline PET/CT and BS before (n = 4) or after (n = 17) treatment. Patient-, region-, and lesion-based diagnostic performances of bone metastasis of both 11C-choline PET/CT and BS were evaluated using a five-point scale by two experienced readers. Bone metastases were present in 11 (52.4%) of 21 patients and 48 (32.7%) of 147 regions; 111 lesions were found to have bone metastases. Region-based analysis showed that the sensitivity, specificity, accuracy, and area under the receiver-operating-characteristic curves (AUC) of 11C-choline PET/CT were 97.9%, 99.0%, 98.6%, and 0.9989, respectively; those of BS were 72.9%, 99.0%, 90.5%, and 0.8386, respectively. Sensitivity, accuracy, and AUC significantly differed between the two methods (McNemar test, p = 0.0015, p = 0.0015, and p PET/CT detected 110/111 metastatic lesions (99.1%); BS detected 85 (76.6%) (p PET/BS were 100%/90.3% for the blastic type, 91.7%/8.3% for the lytic type, 100%/100% for the mixed type, and 100%/53.3% for the invisible type, respectively. Significant differences in blastic, lytic, and invisible types were observed between the two methods (p = 0.013, p = 0.0044, and p = 0.023, respectively). In conclusion, 11C-choline PET/CT had greater sensitivity and accuracy than BS for detection of bone involvement in patients with prostate cancer.

  7. Effects of in ovo administration of betaine and choline on hatchability results, growth and carcass characteristics and immune response of broiler chickens

    Directory of Open Access Journals (Sweden)

    Jafar Gholami

    2015-05-01

    Full Text Available The effect of in ovo administration of different levels of betaine and choline on egg hatchability, immune response, growth and carcass traits of broiler chickens was studied. Four thousand hatching eggs from Ross 308 broiler breeder layers, weighed individually, were incubated for 21 days in a commercial hatchery. At 12th day of incubation, 3456 fertilized eggs were randomly divided into 8 experimental groups of 3 replicates each (144 eggs per replicate: negative control (NC – not injected; positive control (PC – injected with 0.5 mL deionized water; Bet 0.25 – injected with 0.5 mL deionized water+0.25 mg soluble betaine; Bet 0.375 – injected with 0.5 mL deionized water+0.375 mg soluble betaine; Bet 0.50 – injected with 0.5 mL deionized water+0.50 mg soluble betaine; Chol 0.25 – injected with 0.5 mL deionized water+0.25 mg soluble choline; Chol 0.375 – injected with 0.5 mL deionized water+0.375 mg soluble choline; Chol 0.50 – injected with 0.5 mL deionized water+0.50 mg soluble choline. Among the hatched chickens, 360 males were randomly chosen (45 for each group and were grown up to 42nd day of age. The embryo mortality, pecked eggs, infected eggs and hatchability percentages were similar among the experimental groups. The betaine and choline treatments improved hatching weight and final weight of chickens, while reduced feed conversion ratio and abdominal fat percentage. No effect on carcass yield, and breast muscle, leg and wings percentages, as well as on immunoglobulin M (IgM, G (IgG, and total antibody (IgT titers was observed. The treatments had little effect on internal organs.

  8. Imaging primary prostate cancer with 11C-Choline PET/CT: relation to tumour stage, Gleason score and biomarkers of biologic aggressiveness

    International Nuclear Information System (INIS)

    Chen, Ji; Zhao, Yong; Li, Xin; Sun, Peng; Wang, Muwen; Wang, Ridong; Jin, Xunbo

    2012-01-01

    As a significant overlap of 11C-Choline standardized uptake value (SUV) between prostate cancer and benign prostate hyperplasia (BPH) tissue, controversy exists regarding the clinical value of 11C-Choline PET/CT scan in primary prostate cancer. In this study, the SUVmax of the prostate lesions and the pelvic muscles were measured and their ratios (SUVmax-P/M ratio) were calculated. Then we evaluated whether the tracer 11C-Choline uptake, quantified as SUVmax-P/M ratio, correlated with tumour stage, Gleason score, and expression levels of several biomarkers of aggressiveness. Twenty-six patients with primary prostate cancer underwent 11C-Choline PET/CT. Tumour specimens from these patients were graded histopathologically, and immunnohistochemistry for Ki-67, CD31, androgen receptor (AR), Her-2/neu, Bcl-2, and PTEN were performed. Both SUVmax and SUVmax-P/M ratio showed no significant difference between patients with tumour stage II and III, but significantly elevated in patients with tumour stage IV. SUVmax-P/M ratio was also significantly higher in lesions with Gleason score of 4+3 or higher versus less than or equal to 3+4. SUVmax-P/M ratio was found significantly correlated with expression levels of Ki-67 and CD31. In addition, a higher SUVmax-P/M ratio was demonstrated in Her-2/neu positive subgroup than negative subgroup. At the same time, Gleason score and expression levels of these biomarkers showed no significant association with SUVmax. Using the parameter SUVmax-P/M ratio, 11C-Choline PET/CT may be a valuable non-invasive imaging technology in the diagnosis of primary prostate cancer

  9. Prospective head-to-head comparison of {sup 11}C-choline-PET/MR and {sup 11}C-choline-PET/CT for restaging of biochemical recurrent prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Eiber, Matthias [Klinikum rechts der Isar, Department of Nuclear Medicine, Technische Universitaet Muenchen, Munich (Germany); David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles (United States); Rauscher, Isabel; Souvatzoglou, Michael; Schwaiger, Markus [Klinikum rechts der Isar, Department of Nuclear Medicine, Technische Universitaet Muenchen, Munich (Germany); Maurer, Tobias [Klinikum rechts der Isar, Department of Urology, Technische Universitaet Muenchen, Munich (Germany); Holzapfel, Konstantin [Klinikum rechts der Isar, Department of Radiology, Technische Universitaet Muenchen, Munich (Germany); Beer, Ambros J. [Klinikum rechts der Isar, Department of Nuclear Medicine, Technische Universitaet Muenchen, Munich (Germany); Ulm University, Department of Nuclear Medicine, Ulm (Germany)

    2017-12-15

    Whole-body integrated {sup 11}C-choline PET/MR might provide advantages compared to {sup 11}C-choline PET/CT for restaging of prostate cancer (PC) due to the high soft-tissue contrast and the use of multiparametric MRI, especially for detection of local recurrence and bone metastases. Ninety-four patients with recurrent PC underwent a single-injection/dual-imaging protocol with contrast-enhanced PET/CT followed by fully diagnostic PET/MR. Imaging datasets were read separately by two reader teams (team 1 and 2) assessing the presence of local recurrence, lymph node and bone metastases in predefined regions using a five-point scale. Detection rates were calculated. The diagnostic performance of PET/CT vs. PET/MR was compared using ROC analysis. Inter-observer and inter-modality variability, radiation exposure, and mean imaging time were evaluated. Clinical follow-up, imaging, and/or histopathology served as standard of reference (SOR). Seventy-five patients qualified for the final image analysis. A total of 188 regions were regarded as positive: local recurrence in 37 patients, 87 regions with lymph node metastases, and 64 regions with bone metastases. Mean detection rate between both readers teams for PET/MR was 84.7% compared to 77.3% for PET/CT (p > 0.05). Local recurrence was identified significantly more often in PET/MR compared to PET/CT by team 1. Lymph node and bone metastases were identified significantly more often in PET/CT compared to PET/MR by both teams. However, this difference was not present in the subgroup of patients with PSA values ≤2 ng/ml. Inter-modality and inter-observer agreement (K > 0.6) was moderate to substantial for nearly all categories. Mean reduction of radiation exposure for PET/MR compared to PET/CT was 79.7% (range, 72.6-86.2%). Mean imaging time for PET/CT was substantially lower (18.4 ± 0.7 min) compared to PET/MR (50.4 ± 7.9 min). {sup 11}C-choline PET/MR is a robust imaging modality for restaging biochemical recurrent PC

  10. Persistent fibrosis in the liver of choline-deficient and iron-supplemented L-amino acid-defined diet-induced nonalcoholic steatohepatitis rat due to continuing oxidative stress after choline supplementation

    International Nuclear Information System (INIS)

    Takeuchi-Yorimoto, Ayano; Noto, Takahisa; Yamada, Atsushi; Miyamae, Yoichi; Oishi, Yuji; Matsumoto, Masahiro

    2013-01-01

    Nonalcoholic steatohepatitis (NASH) is characterized by combined pathology of steatosis, lobular inflammation, fibrosis, and hepatocellular degeneration, with systemic symptoms of diabetes or hyperlipidemia, all in the absence of alcohol abuse. Given the therapeutic importance and conflicting findings regarding the potential for healing the histopathologic features of NASH in humans, particularly fibrosis, we investigated the reversibility of NASH-related findings in Wistar rats fed a choline-deficient and iron-supplemented L-amino acid-defined (CDAA) diet for 12 weeks, with a recovery period of 7 weeks, during which the diets were switched to a choline-sufficient and iron-supplemented L-amino acid-defined (CSAA) one. Analysis showed that steatosis and inflammation were significantly resolved by the end of the recovery period, along with decreases in AST and ALT activities within 4 weeks. In contrast, fibrosis remained even after the recovery period, to an extent similar to that in continuously CDAA-fed animals. Real-time reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemical investigations revealed that expression of some factors indicating oxidative stress (CYP2E1, 4-HNE, and iNOS) were elevated, whereas catalase and SOD1 were decreased, and a hypoxic state and CD34-positive neovascularization were evident even after the recovery period, although the fibrogenesis pathway by activated α-SMA-positive hepatic stellate cells via TGF-β and TIMPs decreased to the CSAA group level. In conclusion, persistent fibrosis was noted after the recovery period of 7 weeks, possibly due to sustained hypoxia and oxidative stress supposedly caused by capillarization. Otherwise, histopathological features of steatosis and inflammation, as well as serum AST and ALT activities, were recovered. - Highlights: ► NASH-like liver lesions are induced in rats by feeding a CDAA diet. ► Steatosis and lobular inflammation are resolved after switching to a

  11. Persistent fibrosis in the liver of choline-deficient and iron-supplemented L-amino acid-defined diet-induced nonalcoholic steatohepatitis rat due to continuing oxidative stress after choline supplementation

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi-Yorimoto, Ayano, E-mail: ayano.takeuchi@astellas.com [Drug Safety Research Labs, Astellas Pharma Inc., Osaka 532-8514 (Japan); Noto, Takahisa [Drug Safety Research Labs, Astellas Pharma Inc., Osaka 532-8514 (Japan); Yamada, Atsushi [Drug Safety Research Division, Astellas Research Technologies Co., Ltd., Osaka 532-8514 (Japan); Miyamae, Yoichi; Oishi, Yuji; Matsumoto, Masahiro [Drug Safety Research Labs, Astellas Pharma Inc., Osaka 532-8514 (Japan)

    2013-05-01

    Nonalcoholic steatohepatitis (NASH) is characterized by combined pathology of steatosis, lobular inflammation, fibrosis, and hepatocellular degeneration, with systemic symptoms of diabetes or hyperlipidemia, all in the absence of alcohol abuse. Given the therapeutic importance and conflicting findings regarding the potential for healing the histopathologic features of NASH in humans, particularly fibrosis, we investigated the reversibility of NASH-related findings in Wistar rats fed a choline-deficient and iron-supplemented L-amino acid-defined (CDAA) diet for 12 weeks, with a recovery period of 7 weeks, during which the diets were switched to a choline-sufficient and iron-supplemented L-amino acid-defined (CSAA) one. Analysis showed that steatosis and inflammation were significantly resolved by the end of the recovery period, along with decreases in AST and ALT activities within 4 weeks. In contrast, fibrosis remained even after the recovery period, to an extent similar to that in continuously CDAA-fed animals. Real-time reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemical investigations revealed that expression of some factors indicating oxidative stress (CYP2E1, 4-HNE, and iNOS) were elevated, whereas catalase and SOD1 were decreased, and a hypoxic state and CD34-positive neovascularization were evident even after the recovery period, although the fibrogenesis pathway by activated α-SMA-positive hepatic stellate cells via TGF-β and TIMPs decreased to the CSAA group level. In conclusion, persistent fibrosis was noted after the recovery period of 7 weeks, possibly due to sustained hypoxia and oxidative stress supposedly caused by capillarization. Otherwise, histopathological features of steatosis and inflammation, as well as serum AST and ALT activities, were recovered. - Highlights: ► NASH-like liver lesions are induced in rats by feeding a CDAA diet. ► Steatosis and lobular inflammation are resolved after switching to a

  12. Calixarene-mediated liquid membrane transport of choline conjugates 3: The effect of handle variation on neurotransmitter transport.

    Science.gov (United States)

    Collins, James L; Fujii, Ayu; Roshandel, Sahar; To, Cuong-Alexander; Schramm, Michael P

    2017-07-01

    Upper rim phosphonic acid functionalized calix[4]arene affects selective transport of multiple molecular payloads through a liquid membrane. The secret is in the attachment of a receptor-complementary handle to the payload. We find that the trimethylammonium ethylene group present in choline is one of several general handles for the transport of drug and drug-like species. Herein we compare the effect of handle variation against the transport of serotonin and dopamine. We find that several ionizable amine termini handles are sufficient for transport and identify two ideal candidates. Their performance is significantly enhanced in HEPES buffered solutions. This inquiry completes a series of 3 studies aimed at optimization of this strategy. In completion a new approach towards synthetic receptor mediated selective small molecule transport has emerged; future work in vesicular and cellular systems will follow. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Choline but not its derivative betaine blocks slow vacuolar channels in the halophyte Chenopodium quinoa: implications for salinity stress responses.

    Science.gov (United States)

    Pottosin, Igor; Bonales-Alatorre, Edgar; Shabala, Sergey

    2014-11-03

    Activity of tonoplast slow vacuolar (SV, or TPC1) channels has to be under a tight control, to avoid undesirable leak of cations stored in the vacuole. This is particularly important for salt-grown plants, to ensure efficient vacuolar Na(+) sequestration. In this study we show that choline, a cationic precursor of glycine betaine, efficiently blocks SV channels in leaf and root vacuoles of the two chenopods, Chenopodium quinoa (halophyte) and Beta vulgaris (glycophyte). At the same time, betaine and proline, two major cytosolic organic osmolytes, have no significant effect on SV channel activity. Physiological implications of these findings are discussed. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  14. Characterization of new eye drops with choline salicylate and assessment of their irritancy by in vitro short time exposure tests.

    Science.gov (United States)

    Wroblewska, Katarzyna; Kucinska, Małgorzata; Murias, Marek; Lulek, Janina

    2015-09-01

    The aim of our study was to examine the irritation potential of new eye drops containing 2% choline salicylate (CS) as an active pharmaceutical ingredient (API) and various polymers increasing eye drop viscosity (hydroxyethylcellulose, hydroxypropyl methylcellulose, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone). The standard method for assessing the potential of irritating substances has been the Draize rabbit eye test. However the European Centre for Validation of Alternative Methods and the Coordinating Committee for Validation of Alternative Methods recommend, short time exposure (STE) in vitro tests as an alternative method for assessing eye irritation. The eye irritation potential was determined using cytotoxicity test methods for rabbit corneal cell line (SIRC) after 5 min exposure. The viability of cells was determined using two cytotoxicity assays: MTT and Neutral Red Uptake. According to the irritation rankings for the short time exposure test, all tested eye drops are classified as non-irritating (cell viability >70%).

  15. In vivo 19F-MRS observation of 5-FU metabolism in fatty liver induced by choline-deficient diet

    International Nuclear Information System (INIS)

    Otsuka, Hideki; Harada, Masafumi; Nishitani, Hiromu; Koga, Keiko.

    1996-01-01

    Using 19 F-MRS, 5-FU metabolism was investigated in rat fatty liver. Fatty liver was induced by choline-deficient diet (CD diet). This study showed differences in 5-FU metabolism between normal and fatty liver. After laparotomy, a surface coil was placed directly on the liver surface. Spectra were continuously obtained after injection of 5-FU 100 mg/kg body weight via a catheter inserted into femoral vein. We made MRI and 1 H-MRS study to examine the lipid accumulation. Histological study was also performed using HE (hematoxylin-eosin) and oil red stain. The livers of rats fed a CD diet showed very high intensity on T 1 -WI. 1 H-MRS was very useful in deteminating the fat content because the fat ratio demonstrated by 1 H-MRS is well correlated to histological findings. In 19 F-MRS, we recognized the following four peaks: 5-FU, FBAL, Fnct (fluoronucleotide) and FUPA. The decrease of 5-FU was not very apparent, but compared to the normal liver, the formation of Fnct increased and the formation of FBAL was suppressed in fatty liver. The rats fed a CD diet for four weeks showed a higher Fnct peak and lower FBAL peak compared with the results of rats fed a CD diet for two weeks. In a CD diet group, liver cell degeneration and necrotic changes were observed histologically. It is reported that cell degeneration is followed by cell proliferation in fatty liver induced by a choline deficient diet, and the high Fnct peak found in our study may reflect this phenomenon. The high Fnct peak on 19 F-MRS may correspond to recovering reaction from liver injury like fatty liver. (author)

  16. Enzymatic hydrolysis of 1-monoacyl-SN-glycerol-3-phosphoryl-choline (1-lysolecithin) by phospholipases from peanut seeds.

    Science.gov (United States)

    Strauss, H; Leibovitz-Ben Gershon, Z; Heller, M

    1976-06-01

    Hydrolysis of 1-lysolecithin (1-acyl glycerophosphorylcholine [1-acyl GPC]) by preparations of phospholipase D from peanut seeds was investigated. 1-Lysolecithin was hydrolyzed at a much slower rate than phosphatidylcholine (lecithin). Although Ca+2 ions are required for the cleavage of lecithin by the enzyme, their effect on the hydrolysis of lysolecithin depended upon the concentration of the substrate: at 0.2 mM 1-lysolecithin, Ca+2 ions increased the reaction rates, whereas at concentrations of the substrate lower than 0.1 mM, Ca+2 ions were inhibitory. A broad pH activity curve between 5 and 8 was obtained with higher rates in the alkaline range, both in the absence and presence of Ca+2 ions. The increased hydrolysis of lysolecithin due to Ca+2 was noticed over the entire pH range. Upon storage of the enzyme solutions at 4 C, decreased rates of hydrolysis of lecithin were observed, with t 1/2 values of ca. 50 and 100 days depending on the purity of the preparation. During the same period, no reduction occurred in the activity of these preparations on lysolecithin as substrate. The effects of Ca+2 ions and the analysis of the products of 1-acyl GPC cleavage by the enzyme preparations revealed the presence of more than one enzyme and the formation of the following compounds: lysophosphatidic acids (1 acyl glycerophosphoric acids), free fatty acids, glycerophosphorylcholine, and choline. The possible pathways leading to the degradation of lysolecithin and the formation of these products include reactions catalyzed by lysophospholipase A1 (lysophosphatidylcholine 1-acyl hydrolase, E.C. 3.1.1.5) and a phosphodiesterase (L-3-glycerylphosphorylcholine glycerophosphohydrolase, E.C.3.1.4.2), in addition to phospholipase D (phosphatidyl-choline phosphatidohydrolase, E.C. 3.1.4.4).

  17. Vitamin C and Vitamin E in Prevention of Nonalcoholic Fatty Liver Disease (NAFLD in Choline Deficient Diet Fed Rats

    Directory of Open Access Journals (Sweden)

    Lopasso Fabio P

    2003-10-01

    Full Text Available Abstract Aim Oxidative stress has been implicated in the pathogenesis of Nonalcoholic Fatty Liver Disease (NAFLD. Vitamin C and vitamin E are known to react with reactive oxygen species (ROS blocking the propagation of radical reactions in a wide range of oxidative stress situations. The potential therapeutic efficacy of antioxidants in NAFLD is unknown. The aim of this study was to evaluate the role of antioxidant drugs (vitamin C or vitamin E in its prevention. Methods Fatty liver disease was induced in Wistar rats by choline-deficient diet for four weeks. The rats were randomly assigned to receive vitamin E (n = 6 – (200 mg/day, vitamin C (n = 6 (30 mg/Kg/day or vehicle orally. Results In the vehicle and vitamin E-treated rats, there were moderate macro and microvesicular fatty changes in periportal area without inflammatory infiltrate or fibrosis. Scharlach stain that used for a more precise identification of fatty change was strong positive. With vitamin C, there was marked decrease in histological alterations. Essentially, there was no liver steatosis, only hepatocellular ballooning. Scharlach stain was negative. The lucigenin-enhanced luminescence was reduced with vitamin C (1080 ± 330 cpm/mg/minx103 as compared to those Vitamin E and control (2247 ± 790; 2020 ± 407 cpm/mg/minx103, respectively (p Conclusions 1 Vitamin C reduced oxidative stress and markedly inhibited the development of experimental liver steatosis induced by choline-deficient diet ; 2Vitamin E neither prevented the development of fatty liver nor reduced the oxidative stress in this model.

  18. Comparison of {sup 68}Ga-labelled PSMA-11 and {sup 11}C-choline in the detection of prostate cancer metastases by PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Schwenck, Johannes [Eberhard Karls University, Department of Nuclear Medicine and Clinical Molecular Imaging, Tuebingen (Germany); Eberhard Karls University, Department of Preclinical Imaging and Radiopharmacy, Tuebingen (Germany); Rempp, Hansjoerg; Nikolaou, Konstantin; Pfannenberg, Christina [Eberhard Karls University, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany); Reischl, Gerald [Eberhard Karls University, Department of Preclinical Imaging and Radiopharmacy, Tuebingen (Germany); Kruck, Stephan; Stenzl, Arnulf [Eberhard Karls University, Department of Urology, Tuebingen (Germany); La Fougere, Christian [Eberhard Karls University, Department of Nuclear Medicine and Clinical Molecular Imaging, Tuebingen (Germany); German Cancer Consortium, German Cancer Research Center Partner Site, Heidelberg (Germany)

    2017-01-15

    Prostate-specific membrane antigen (PSMA) is expressed ubiquitously on the membrane of most prostate tumors and its metastasis. While PET/CT using {sup 11}C-choline was considered as the gold standard in the staging of prostate cancer, PET with radiolabelled PSMA ligands was introduced into the clinic in recent years. Our aim was to compare the PSMA ligand {sup 68}Ga-PSMA-11 with {sup 11}C-choline in patients with primary and recurrent prostate cancer. 123 patients underwent a whole-body PET/CT examination using {sup 68}Ga-PSMA-11 and {sup 11}C-choline. Suspicious lesions were evaluated visually and semiquantitatively (SUVavg). Out of these, 103 suffered from a confirmed biochemical relapse after prostatectomy and/or radiotherapy (mean PSA level of 4.5 ng/ml), while 20 patients underwent primary staging. In 67 patients with biochemical relapse, we detected 458 lymph nodes suspicious for metastasis. PET using {sup 68}Ga-PSMA-11 showed a significantly higher uptake and detection rate than {sup 11}C-choline PET. Also {sup 68}Ga-PSMA-11 PET identified significantly more patients with suspicious lymph nodes as well as affected lymph nodes regions especially at low PSA levels. Bone lesions suspicious for prostate cancer metastasis were revealed in 36 patients' biochemical relapse. Significantly more bone lesions were detected by {sup 68}Ga-PSMA-11, but only 3 patients had only PSMA-positive bone lesions. Nevertheless, we detected also 29 suspicious lymph nodes and 8 bone lesions, which were only positive as per {sup 11}C-choline PET. These findings led to crucial differences in the TNM classification and the identification of oligometastatic patients. In the patients who underwent initial staging, all primary tumors showed uptake of both tracers. Although significantly more suspicious lymph nodes and bone lesions were identified, only 2 patients presented with bone lesions only detected by {sup 68}Ga-PSMA-11 PET. Thus, PET using {sup 68}Ga-PSMA-11 showed a higher

  19. Is There an Additional Value of 11C-Choline PET-CT to T2-weighted MRI Images in the Localization of Intraprostatic Tumor Nodules?

    International Nuclear Information System (INIS)

    Van den Bergh, Laura; Koole, Michel; Isebaert, Sofie; Joniau, Steven; Deroose, Christophe M.; Oyen, Raymond; Lerut, Evelyne; Budiharto, Tom; Mottaghy, Felix; Bormans, Guy; Van Poppel, Hendrik; Haustermans, Karin

    2012-01-01

    Purpose: To investigate the additional value of 11 C-choline positron emission tomography (PET)-computed tomography (CT) to T2-weighted (T2w) magnetic resonance imaging (MRI) for localization of intraprostatic tumor nodules. Methods and Materials: Forty-nine prostate cancer patients underwent T2w MRI and 11 C-choline PET-CT before radical prostatectomy and extended lymphadenectomy. Tumor regions were outlined on the whole-mount histopathology sections and on the T2w MR images. Tumor localization was recorded in the basal, middle, and apical part of the prostate by means of an octant grid. To analyze 11 C-choline PET-CT images, the same grid was used to calculate the standardized uptake values (SUV) per octant, after rigid registration with the T2w MR images for anatomic reference. Results: In total, 1,176 octants were analyzed. Sensitivity, specificity, and accuracy of T2w MRI were 33.5%, 94.6%, and 70.2%, respectively. For 11 C-choline PET-CT, the mean SUV max of malignant octants was significantly higher than the mean SUV max of benign octants (3.69 ± 1.29 vs. 3.06 ± 0.97, p mean values (2.39 ± 0.77 vs. 1.94 ± 0.61, p mean and absolute tumor volume (Spearman r = 0.3003, p = 0.0362). No correlation was found between SUVs and prostate-specific antigen, T-stage or Gleason score. The highest accuracy (61.1%) was obtained with a SUV max cutoff of 2.70, resulting in a sensitivity of 77.4% and a specificity of 44.9%. When both modalities were combined (PET-CT or MRI positive), sensitivity levels increased as a function of SUV max but at the cost of specificity. When only considering suspect octants on 11 C-choline PET-CT (SUV max ≥ 2.70) and T2w MRI, 84.7% of these segments were in agreement with the gold standard, compared with 80.5% for T2w MRI alone. Conclusions: The additional value of 11 C-choline PET-CT next to T2w MRI in detecting tumor nodules within the prostate is limited.

  20. Chronic treatment with amyloid beta(1-42) inhibits non-cholinergic high-affinity choline transport in NG108-15 cells through protein kinase C signaling

    Czech Academy of Sciences Publication Activity Database

    Nováková, Jana; Mikasová, Lenka; Machová, Eva; Lisá, Věra; Doležal, Vladimír

    2005-01-01

    Roč. 1062, č. 1-2 (2005), s. 101-110 ISSN 0006-8993 R&D Projects: GA AV ČR(CZ) IAA5011206; GA MŠk(CZ) LC554 Grant - others:Lipidiet(XE) QLK1-CT-2002-00172 Institutional research plan: CEZ:AV0Z50110509 Keywords : choline transporter * beta-amyloid * protein kinase C Subject RIV: ED - Physiology Impact factor: 2.296, year: 2005

  1. Simple determination of betaine, l-carnitine and choline in human urine using self-packed column and column-switching ion chromatography with nonsuppressed conductivity detection.

    Science.gov (United States)

    Wei, Dan; Zhu, Yan; Guo, Ming

    2018-02-01

    A sequential online extraction, clean-up and separation system for the determination of betaine, l-carnitine and choline in human urine using column-switching ion chromatography with nonsuppressed conductivity detection was developed in this work. A self-packed pretreatment column (50 × 4.6 mm, i.d.) was used for the extraction and clean-up of betaine, l-carnitine and choline. The separation was achieved using self-packed cationic exchange column (150 × 4.6 mm, i.d.), followed by nonsuppressed conductivity detection. Under optimized experimental conditions, the developed method presented good analytical performance, with excellent linearity in the range of 0.60-100 μg mL -1 for betaine, 0.75-100 μg mL -1 for l-carnitine and 0.50-100 μg mL -1 for choline, with all correlation coefficients (R 2 ) >0.99 in urine. The limits of detection were 0.15 μg mL -1 for betaine, 0.20 μg mL -1 for l-carnitine and 0.09 μg mL -1 for choline. The intra- and inter-day accuracy and precision for all quality controls were within ±10.32 and ±9.05%, respectively. Satisfactory recovery was observed between 92.8 and 102.0%. The validated method was successfully applied to the detection of urinary samples from 10 healthy people. The values detected in human urine using the proposed method showed good agreement with the measurement reported previously. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Determination of betaine, l-carnitine, and choline in human urine using a self-packed column and column-switching ion chromatography with nonsuppressed conductivity detection.

    Science.gov (United States)

    Wei, Dan; Liu, Junwei; Guo, Ming; Zhu, Yan

    2017-11-01

    A simple method for the determination of betaine, l-carnitine, and choline in human urine was developed based on column-switching ion chromatography coupled with nonsuppressed conductivity detection by using a self-packed column. A pretreatment column (50 mm × 4.6 mm, id) packed with poly(glycidyl methacrylate-divinylbenzene) microspheres was used for the extraction and cleanup of analytes. Chromatographic separation was achieved within 10 min on a cationic exchange column (150 mm × 4.6 mm, id) using maleic anhydride modified poly(glycidyl methacrylate-divinylbenzene) as the particles for packing. The detection was performed by ion chromatography with nonsuppressed conductivity detection. Parameters including column-switching time, eluent type, flow rates of eluent, and interfering effects were optimized. Linearity (r 2 ≥ 0.99) was obtained for the concentration range of 0.50-100, 0.75-100, and 0.25-100 μg/mL for betaine, l-carnitine, and choline, respectively. Detection limits were 0.12, 0.20, and 0.05 μg/mL for betaine, l-carnitine, and choline, respectively. The intra- and interday accuracy and precision for all quality controls were within ±10.11%. Satisfactory recovery was observed between 92.5 and 105.0%. The validated method was successfully applied for the determination of betaine, l-carnitine, and choline in urine samples from healthy people. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Diagnostic value of combining {sup 11}C-choline and {sup 18}F-FDG PET/CT in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Castilla-Lievre, Maria-Angela [University Department Hepatinov, Assistance-Publique Hopitaux de Paris, Department of Nuclear Medicine, Hopital Antoine Beclere, Clamart (France); IMIV - UMR 1023 Inserm/CEA/Universite Paris Sud - ERL 9218 CNRS, Orsay (France); Franco, Dominique [Universite Paris-Sud, Department of Surgery, Hopital Antoine Beclere, University Department Hepatinov, Assistance-Publique Hopitaux de Paris, Clamart (France); Gervais, Philippe; Kuhnast, Bertrand; Desarnaud, Serge; Helal, Badia-Ourkia [IMIV - UMR 1023 Inserm/CEA/Universite Paris Sud - ERL 9218 CNRS, Orsay (France); CEA, DSV, I2BM, Service Hospitalier Frederic Joliot, Orsay (France); Agostini, Helene [University Department Hepatinov, Assistance-Publique Hopitaux de Paris, Clinical Research Unit of Hopitaux universitaires Paris-Sud, Hopital Kremlin Bicetre (France); Marthey, Lysiane [Universite Paris-Sud, Department of Gastroenterology, Hopital Antoine Beclere, University Department Hepatinov, Assistance-Publique Hopitaux de Paris, Clamart (France)

    2016-05-15

    In this prospective study, our goal was to emphasize the diagnostic value of combining {sup 11}C-choline and {sup 18}F-FDG PET/CT for hepatocellular carcinoma (HCC) in patients with chronic liver disease. Thirty-three consecutive patients were enrolled. All patients were suspected to have HCC based on CT and/or MRI imaging. A final diagnosis was obtained by histopathological examination or by imaging alone according to American Association for the Study of Liver Disease criteria. All patients underwent PET/CT with both tracers within a median of 5 days. All lesions showing higher tracer uptake than normal liver were considered positive for HCC. We examined how tracer uptake was related to biological (serum α-fetoprotein levels) and pathological (differentiation status, peritumoral capsule and vascular invasion) prognostic markers of HCC, as well as clinical observations at 6 months (recurrence and death). Twenty-eight HCC, four cholangiocarcinomas and one adenoma were diagnosed. In the HCC patients, the sensitivity of {sup 11}C-choline, {sup 18}F-FDG and combined {sup 11}C-choline and {sup 18}F-FDG PET/CT for the detection of HCC was 75 %, 36 % and 93 %, respectively. Serum α-fetoprotein levels >200 ng/ml were more frequent among patients with {sup 18}F-FDG-positive lesions than those with {sup 18}F-FDG-negative lesions (p < 0.05). Early recurrence (n=2) or early death (n=5) occurred more frequently in patients with {sup 18}F-FDG-positive lesions than in those with {sup 18}F-FDG-negative lesions (p < 0.05). The combined use of {sup 11}C-choline and {sup 18}F-FDG PET/CT detected HCC with high sensitivity. This approach appears to be of potential prognostic value and may facilitate the selection of patients for surgical resection or liver transplantation. (orig.)

  4. Supplementation with Folic Acid, but Not Creatine, Increases Plasma Betaine, Decreases Plasma Dimethylglycine, and Prevents a Decrease in Plasma Choline in Arsenic-Exposed Bangladeshi Adults.

    Science.gov (United States)

    Hall, Megan N; Howe, Caitlin G; Liu, Xinhua; Caudill, Marie A; Malysheva, Olga; Ilievski, Vesna; Lomax-Luu, Angela M; Parvez, Faruque; Siddique, Abu B; Shahriar, Hasan; Uddin, Mohammad N; Islam, Tariqul; Graziano, Joseph H; Gamble, Mary V

    2016-05-01

    Folic acid (FA) supplementation facilitates urinary excretion of arsenic, a human carcinogen. A better understanding of interactions between one-carbon metabolism intermediates may improve the ability to design nutrition interventions that further facilitate arsenic excretion. The objective was to determine if FA and/or creatine supplementation increase choline and betaine and decrease dimethylglycine (DMG). We conducted a secondary analysis of the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults (n = 605, aged 24-55 y, 50.3% male) who received arsenic-removal water filters. We examined treatment effects of FA and/or creatine supplementation on plasma choline, betaine, and DMG concentrations, measured by LC-tandem mass spectrometry at baseline and at week 12. Group comparisons were between 1) 400 and 800 μg FA/d (FA400 and FA800, respectively) compared with placebo, 2) creatine (3 g/d) compared with placebo, and 3) creatine plus FA400 compared with FA400. Choline decreased in the placebo group (-6.6%; 95% CI: -10.2%, -2.9%) but did not change in the FA groups (FA400: 2.5%; 95% CI: -0.9%, 6.1%; FA800: 1.4%; 95% CI: -2.5%, 5.5%; P creatine treatment arms and their respective reference groups. Supplementation for 12 wk with FA, but not creatine, increases plasma betaine, decreases plasma DMG, and prevents a decrease in plasma choline in arsenic-exposed Bangladeshi adults. This trial was registered at clinicaltrials.gov as NCT01050556. © 2016 American Society for Nutrition.

  5. Therapeutic Efficacy of Fenugreek Extract or/and Choline with Docosahexaenoic Acid in Attenuating Learning and Memory Deficits in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Anjaneyulu K

    2018-04-01

    Full Text Available Background: Studies have demonstrated that estradiol influences cognitive functions. Phytoestrogens and many other estrogen-like compounds in plants have beneficial effects on cognitive performance in postmenopausal women. However, there is no evident report of fenugreek and choline-Docosahexaenoic Acid (DHA on cognition in ovariectomized rats. Aim and Objectives: The present study was aimed to evaluate the therapeutic efficacy of fenugreek extract or/and choline- DHA in attenuating ovariectomy-induced memory impairment, brain antioxidant status and hippocampal neural cell deficits in the rat model. Material and Methods: Female Wistar 9-10 months old rats were grouped (n=12/group as - (1 Normal Control (NC, (2 Ovariectomized (OVX, (3 OVX+FG (hydroalcoholic seed extract of fenugreek, (4 OVX+C-DHA,(5 OVX+FG+C-DHA and (6 OVX+Estradiol. Groups 2- 6 were bilaterally OVX. FG, C-DHA was supplemented orally for 30 days, 14 days after ovariectomy. Assessment of learning and memory was performed by passive avoidance test. Oxidative stress and antioxidant markers were assessed by standard methods. Nissl stained hippocampal sections were analyzed to determine alterations in neural cell numbers in CA1, CA3 and dentate gyrus. Results: Supplementation of FG or/and choline with DHA to OVX rats, caused significant improvement in learning and memory as well as decreased neural cell deficits compared to the same in OVX rats. Further, significantly reduced levels of brain Malondialdehyde (MDA and increased levels of Glutathione (GSH were observed. Conclusion: Therapeutic supplementation of FG with choline-DHA significantly attenuates ovariectomy-induced neurocognitive deficits in rats.

  6. Comparison between the efficacies of curcumin and puerarin in C57BL/6 mice with steatohepatitis induced by a methionine- and choline-deficient diet

    OpenAIRE

    WANG, YUNLIANG; LI, JIAN; ZHUGE, LI; SU, DONGMEI; YANG, MEIJUAN; TAO, SHIYING; LI, JUNXIANG

    2013-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a prevalent disease, which features an abnormal accumulation of lipids inside hepatocytes. Steatohepatitis plays a critical role in the process resulting in liver fibrosis and cirrhosis. Curcumin and puerarin are herbal products widely used in Asia, which are believed to have therapeutic benefits for alleviating the symptoms of steatohepatitis. In this study, mice models of steatohepatitis induced by a methionine- and choline-deficient diet (MCD) w...

  7. New Acquisition Protocol of 18F-Choline PET/CT in Prostate Cancer Patients: Review of the Literature about Methodology and Proposal of Standardization

    Directory of Open Access Journals (Sweden)

    Sotirios Chondrogiannis

    2014-01-01

    Full Text Available Purpose. (1 To evaluate a new acquisition protocol of 18F-choline (FCH PET/CT for prostate cancer patients (PC, (2 to review acquisition 18F-choline PET/CT methodology, and (3 to propose a standardized acquisition protocol on FCH PET/CT in PC patients. Materials. 100 consecutive PC patients (mean age 70.5 years, mean PSA 21.35 ng/mL were prospectively evaluated. New protocol consisted of an early scan of the pelvis immediately after the injection of the tracer (1 bed position of 4 min followed by a whole body scan at one 1 hour. Early and 1 hour images were compared for interfering activity and pathologic findings. Results. The overall detection rate of FCH PET/CT was 64%. The early static images of the pelvis showed absence of radioactive urine in ureters, bladder, or urethra which allowed a clean evaluation of the prostatic fossae. Uptake in the prostatic region was better visualized in the early phase in 26% (7/30 of cases. Other pelvic pathologic findings (bone and lymph nodes were visualized in both early and late images. Conclusion. Early 18F-choline images improve visualization of abnormal uptake in prostate fossae. All pathologic pelvic deposits (prostate, lymph nodes, and bone were visualized in both early and late images.

  8. Effects of ginsenoside of stem and leaf combined with choline on learning and memory ability of rat models with Alzheimer diseases

    Institute of Scientific and Technical Information of China (English)

    Xiaomin Zhao; Xianglin Xie; Zuoli Xia; Yunsheng Gao; Yuyun Zhu; Hongxia Gu

    2006-01-01

    BACKGROUND: Central adrenergic nerve and 5-serotonergic nerve can influence central cholinergic nerve on learning and memory and make easy for study; however, ginsenoside of stem and leaf (GSL) can improve functions of central adrenergic nerve; moreover, 5-serotonergic nerve and the combination with choline can produce synergistic effect and enhance learning and memory ability so as to improve learning and memory disorder of patients with Alzheimer disease (AD).OBJECTIVE: To observe the effects of GSL combining with choline on learning and memory of AD model rats.DESIGN: Randomized grouping design and controlled animal study.SETTING: Department of Pharmacology, Taishan Medical College.MATERIALS: The experiment was carried out in the Pharmacological Department of Medical College of Jilin University from October 1996 to January 1997. Forty healthy male Wistar rats of clean grade were randomly divided into 5 groups, including sham-injury group, model group, GSL group, choline group and combination group, with 8 rats in each group. Main medications: GSL with the volume more than 92.8% was provided by Department of Chemistry, Norman Bethune Medical College of Jilin University. Panaxatriol, the main component, was detected with thin layer scanning technique and regarded as the index of GSL quality [(55±1)%, CV= 2%, n= 5]. Choline was provided by the Third Shanghai Laboratory Factory.METHODS: 150 nmol quinolinic acid was used to damage bilateral Meynert basal nuclei of adult rats so as to establish AD models. Rats in GSL, choline and combination groups were intragastric administrated with 400 mg/kg GSL, 200 mg/kg choline (20 mL/kg), and both respectively last for 17 days starting from two days 400 mg/kg GSL, 200 mg/kg choline (20 mL/kg), and both respectively last for 17 days starting from two days before operation. Rats in sham-injury group and model group were perfused with the same volume of distilled jumped up safe platform when they were shocked with 36 V

  9. Incorporation of radioactive labelled cholin and palmitate into lung lecithin of rabbits treated with high doses of bromcarbamides, barbiturates and diazepam

    International Nuclear Information System (INIS)

    Wichert, P. von; Schmidt, C.; Pomraenke, K.; Wiegers, U.

    1977-01-01

    Severe intoxications with bromcarbamides often show respiratory complications. To answer the question if there is a direct effect of the drug on lung tissue the incorporation of radioactive labelled choline and palmitate into lung lecithin was investigated. The phospholipid metabolism is in close relation to the surfactant system of the lung. Secondly the influence of bromcarbamides was compared with other hypnotic drugs. There was a reduction of palmitate incorporation into lung lecithin down to 40%, whereas the incorporation of choline increases in bromcarbamide intoxication. The relation between palmitate and choline incorporation was 6.77 in the controls and it decreases to 2-3 in the bromcarbamide group. The total phospholipid content in the lung/g wet weight remained unchanged in all experiments. From this data it is concluded, that these drugs cause a reduction of fatty acid exchange of the lecithin molecules of the lung. This might lead to the production of non surface active lecithin. The clinical and the morphological aspects of severe bromcarbamide intoxication are consistent with a perturbation of the surfactant function. (orig./MG) [de

  10. Prospective Comparison of F-18 Choline PET/CT Scan Versus Axial MRI for Detecting Bone Metastasis in Biochemically Relapsed Prostate Cancer Patients

    Directory of Open Access Journals (Sweden)

    Wouter Huysse

    2017-10-01

    Full Text Available We compared fluor-18 choline positron emission tomography/computed tomography (PET/CT and axial skeleton magnetic resonance imaging (MRI prospectively obtained for the detection of bone metastases in non-castrated patients with biochemically recurrent prostate cancer following primary treatment. PET/CT was performed 45 min post-injection of 3–4 MBq/kg F-18 methyl choline. MRI included T1- and fluid sensitive T2-weighted images of the spine and pelvis. Readers were initially blinded from other results and all scans underwent independent double reading. The best valuable comparator (BVC defined the metastatic status. On the basis of the BVC, 15 out of 64 patients presented with 24 bone metastases. On a patient level, the sensitivity and specificity of MRI and PET were not significantly different. On a lesion level, the sensitivity of MRI was significantly better compared to PET, and the specificity did not differ significantly. In conclusion, axial MRI is an interesting screening tool for the detection of bone metastases because of its low probability of false negative results. However, F-18 choline PET is a valuable addition as it can overrule false positive MRI results and detect non-axial metastases.

  11. Magnetic graphene oxide modified with choline chloride-based deep eutectic solvent for the solid-phase extraction of protein

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Yanhua; Wang, Yuzhi, E-mail: wyzss@hnu.edu.cn; Pan, Qi; Wang, Ying; Ding, Xueqin; Xu, Kaijia; Li, Na; Wen, Qian

    2015-06-02

    Highlights: • A strategy for extraction of protein based on DES-coated magnetic graphene oxide. • The deep eutectic solvents were based on choline chloride. • Bovine serum albumin was used as the analyte. • The material prepared works for the acidic but not the basic or the neutral proteins. - Abstract: Four kinds of green deep eutectic solvents (DESs) based on choline chloride (ChCl) have been synthesized and coated on the surface of magnetic graphene oxide (Fe{sub 3}O{sub 4}@GO) to form Fe{sub 3}O{sub 4}@GO-DES for the magnetic solid-phase extraction of protein. X-ray diffraction (XRD), vibrating sample magnetometer (VSM), Fourier transform infrared spectrometry (FTIR), field emission scanning electron microscopy (FESEM) and thermal gravimetric analysis (TGA) were employed to characterize Fe{sub 3}O{sub 4}@GO-DES, and the results indicated the successful preparation of Fe{sub 3}O{sub 4}@GO-DES. The UV–vis spectrophotometer was used to measure the concentration of protein after extraction. Single factor experiments proved that the extraction amount was influenced by the types of DESs, solution temperature, solution ionic strength, extraction time, protein concentration and the amount of Fe{sub 3}O{sub 4}@GO-DES. Comparison of Fe{sub 3}O{sub 4}@GO and Fe{sub 3}O{sub 4}@GO-DES was carried out by extracting bovine serum albumin, ovalbumin, bovine hemoglobin and lysozyme. The experimental results showed that the proposed Fe{sub 3}O{sub 4}@GO-DES performs better than Fe{sub 3}O{sub 4}@GO in the extraction of acidic protein. Desorption of protein was carried out by eluting the solid extractant with 0.005 mol L{sup −1} Na{sub 2}HPO{sub 4} contained 1 mol L{sup −1} NaCl. The obtained elution efficiency was about 90.9%. Attributed to the convenient magnetic separation, the solid extractant could be easily recycled.

  12. SU-F-J-101: Stereotactic Body Radiation Therapy Planning for Primary Prostate Cancer with Selective Intraprostatic Boost Determined by 18F-Choline PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Wu, L [Cancer Hospital of Shantou University Medical College, Shantou, Guangdong (China); Wang, H; Kuang, Y [University of Nevada Las Vegas, Las Vegas, NV (United States); Hirata, E; Kwee, S [Queen’s Medical Center, Honolulu, HI (United States)

    2016-06-15

    Purpose: To investigate the utility of {sup 18}F-choline positron emission tomography (PET) scans guidance for SBRT dose painting in patients with prostate cancer and its impact on tumor control probability (TCP) and normal tissue complication probability (NTCP). Methods: Twenty seven patients with localized prostate cancer who had {sup 18}F-choline PET/CT scan prior to treatment were included. A pair of nested intraprostatic dominant lesion (IDL) contours (IDL{sub suv60%} and IDL{sub suv70%}) were generated for each patient based on 60% and 70% of maximum prostate uptake on the {sup 18}F-choline PET images. GTV{sub reg} was delineated on prostate according to the gland boundary seen on CT images. The PTVs (PTV{sub suv60%} and PTV{sub suv70%}) were defined as respective IDLs with a 3-mm margin posteriorly and 5 mm in all other dimensions. Two 5-fraction SBRT plans using VMAT technique along with 10 MV FFF beams, plan{sub 36Gy} and plan{sub 50–55Gy}, were generated for each patient. All plans included a dose of 36.25 Gy prescribed to PTV{sub reg}. The Plan{sub 50–55Gy} also included a simultaneous boost dose of 50 Gy and 55 Gy prescribed to the PTV{sub suv60%} and PTV{sub suv70%}, respectively. The utility of {sup 18}F-Choline PET-guided SBRT dose escalation was evaluated by its ability to achieve the prescription dose objectives while adhering to organ-at-risk (OAR) dose constraints. The TCP and NTCP calculated by radiological models were also compared between two plans for each patient. Results: In all 54 SBRT plans generated, the planning objectives and dose constraints were met without exception. Plan{sub 50–55Gy} had a significantly higher dose in PTV{sub suv60%} and PTV{sub suv70%} than those in Plan{sub 36Gy} (p < 0.05), respectively, while still maintaining a safe OAR sparing profile. In addition, plan{sub 50–55Gy} had significantly higher TCP than plan{sub 36Gy}. Conclusion: Using VMAT with FFF beams to incorporate a simultaneous {sup 18}F-choline

  13. Fully automated preparation of [11C]choline and [18F]fluoromethylcholine using TracerLab synthesis modules and facilitated quality control using analytical HPLC

    International Nuclear Information System (INIS)

    Shao Xia; Hockley, Brian G.; Hoareau, Raphael; Schnau, Paul L.; Scott, Peter J.H.

    2011-01-01

    Modifications of a GE TracerLab FX C-Pro , which can be implemented for solid-phase [ 11 C]methylation are described. The simplified procedure for synthesis of [ 11 C]choline uses a single Sep-Pak CM-Light cation-exchange cartridge for both solid-supported reaction and purification. Compared with the commonly used two Sep-Pak method, the low back-pressure of this Sep-Pak enables efficient and reliable production of [ 11 C]choline using a TracerLab FX C-Pro without requirement for any gas pressure adjustment. Typical radiochemical yields (RCY) are >60%, radiochemical purity (RCP) is 99.9% and levels of residual precursor in the final product, which may inhibit the uptake of [ 11 C]choline, are reduced to 1 μg/mL. Similarly, modification of a GE TracerLab FX FN is reported which enables gas-phase production of [ 18 F]fluoromethylcholine, suitable for pre-clinical use, (in 4-6% RCY and >99.7% RCP) using a related Sep-Pak method. These modifications can be utilized for solid-phase [ 11 C]methylation and [ 18 F]fluoromethylation of other radiotracers, and allow straightforward switching to other module configurations for solution-phase radiochemistry or loop chemistry. In addition, we report a convenient HPLC ion chromatography method, which can monitor residual precursor and the radiochemical purity of product at the same time, providing highly efficient quality control for routine clinical application. The reported HPLC method is appropriate for analysis of doses of both [ 11 C]choline and [ 18 F]fluoromethylcholine, and eliminates the need for a GC method to determine residual precursor levels. -- Graphical abstract: Simplified procedures for the automated synthesis of [ 11 C]choline and [ 18 F]fluoromethylcholine using TracerLab FX C-Pro and TracerLab FX FN synthesis modules are presented. In addition, we report a convenient HPLC ion chromatography method, which can monitor residual precursor and radiochemical purity of the product at the same time. Display Omitted

  14. Bienzymatic Acetylcholinesterase and Choline Oxidase Immobilized Biosensor Based on a Phenyl Carboxylic Acid-Grafted Multiwalled Carbon Nanotube

    Directory of Open Access Journals (Sweden)

    So-Ra Lee

    2014-01-01

    Full Text Available Bienzymatic acetylcholinesterase (AChE and choline oxidase (ChOx immobilized biosensor based on a phenyl carboxylic acid-grafted multiwalled carbon nanotube (MWNT modified glass carbon electrode (GCE and carbon-screen printed electrode (SPE was fabricated for acetylcholine detection in human blood samples. Phenyl carboxylic acid-modified MWNT supports were prepared by electrochemical polymerization of 4-carboxyphenyl diazonium salts, which were synthesized by an amine group and sodium nitrite, on the surface of the MWNT-modified GCE and SPE in 0.1 M PBS. The successful fabrication of the AChE-ChOx-immobilized biosensor was confirmed via scanning electron microscopy (SEM, X-ray photoelectron spectroscopy (XPS, electrochemical impedance spectroscopy (EIS, and cyclic voltammetry (CV. The sensing range of the biosensor based on a GCE and SPE was 1.0~10 μM and 10~100 μM, respectively. The interfering effect of 0.1 M L-ascorbic acid, 0.1 M L-cysteine, and 0.1 M uric acid to 0.1 M acetylcholine was 3.00%, 9.00%, and 3.00%, respectively. Acetylcholine in a human blood sample was detected by the AChE-ChOx-immobilized biosensor.

  15. Co-expression of GAD67 and choline acetyltransferase reveals a novel neuronal phenotype in the mouse medulla oblongata.

    Science.gov (United States)

    Gotts, Jittima; Atkinson, Lucy; Edwards, Ian J; Yanagawa, Yuchio; Deuchars, Susan A; Deuchars, Jim

    2015-12-01

    GABAergic and cholinergic systems play an important part in autonomic pathways. To determine the distribution of the enzymes responsible for the production of GABA and acetylcholine in areas involved in autonomic control in the mouse brainstem, we used a transgenic mouse expressing green fluorescent protein (GFP) in glutamate decarboxylase 67 (GAD67) neurones, combined with choline acetyl transferase (ChAT) immunohistochemistry. ChAT-immunoreactive (IR) and GAD67-GFP containing neurones were observed throughout the brainstem. A small number of cells contained both ChAT-IR and GAD67-GFP. Such double labelled cells were observed in the NTS (predominantly in the intermediate and central subnuclei), the area postrema, reticular formation and lateral paragigantocellular nucleus. All ChAT-IR neurones in the area postrema contained GAD67-GFP. Double labelled neurones were not observed in the dorsal vagal motor nucleus, nucleus ambiguus or hypoglossal nucleus. Double labelled ChAT-IR/GAD67-GFP cells in the NTS did not contain neuronal nitric oxide synthase (nNOS) immunoreactivity, whereas those in the reticular formation and lateral paragigantocellular nucleus did. The function of these small populations of double labelled cells is currently unknown, however their location suggests a potential role in integrating signals involved in oromotor behaviours. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Neuropeptide Y-like immunoreactivity in rat cranial parasympathetic neurons: coexistence with vasoactive intestinal peptide and choline acetyltransferase

    International Nuclear Information System (INIS)

    Leblanc, G.C.; Trimmer, B.A.; Landis, S.C.

    1987-01-01

    Neuropeptide Y (NPY) is widely distributed in the sympathetic nervous system, where it is colocalized with norepinephrine. The authors report here that NPY-immunoreactive neurons are also abundant in three cranial parasympathetic ganglia, the otic, sphenopalatine, and ciliary, in the rat measured by radioimmunoassay. High-performance liquid chromatographic analysis of the immunoreactive material present in the otic ganglion indicates that this material is very similar to porcine NPY and indistinguishable from the NPY-like immunoreactivity present in rat sympathetic neurons. These findings raise the possibility that NPY acts as a neuromodulator in the parasympathetic as well as the sympathetic nervous system. In contrast to what had been observed for sympathetic neurons, NPY-immunoreactive neurons in cranial parasympathetic ganglia do not contain detectable catecholamines or tyrosine hydroxylase immunoreactivity, and many do contain immunoreactivity for vasoactive intestinal peptide and/or choline acetyltransferase. These findings suggest that there is no simple rule governing coexpression of NPY with norepinephrine, acetylcholine, or vasoactive intestinal peptide in autonomic neurons. Further, while functional studies have indicated that NPY exerts actions on the peripheral vasculature which are antagonistic to those of acetylcholine and vasoactive intestinal peptide, the present results raise the possibility that these three substances may have complementary effects on other target tissues

  17. Adolescent, but not adult, binge ethanol exposure leads to persistent global reductions of choline acetyltransferase expressing neurons in brain.

    Directory of Open Access Journals (Sweden)

    Ryan P Vetreno

    Full Text Available During the adolescent transition from childhood to adulthood, notable maturational changes occur in brain neurotransmitter systems. The cholinergic system is composed of several distinct nuclei that exert neuromodulatory control over cognition, arousal, and reward. Binge drinking and alcohol abuse are common during this stage, which might alter the developmental trajectory of this system leading to long-term changes in adult neurobiology. In Experiment 1, adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-day on/2-day off from postnatal day [P] 25 to P55 treatment led to persistent, global reductions of choline acetyltransferase (ChAT expression. Administration of the Toll-like receptor 4 agonist lipopolysaccharide to young adult rats (P70 produced a reduction in ChAT+IR that mimicked AIE. To determine if the binge ethanol-induced ChAT decline was unique to the adolescent, Experiment 2 examined ChAT+IR in the basal forebrain following adolescent (P28-P48 and adult (P70-P90 binge ethanol exposure. Twenty-five days later, ChAT expression was reduced in adolescent, but not adult, binge ethanol-exposed animals. In Experiment 3, expression of ChAT and vesicular acetylcholine transporter expression was found to be significantly reduced in the alcoholic basal forebrain relative to moderate drinking controls. Together, these data suggest that adolescent binge ethanol decreases adult ChAT expression, possibly through neuroimmune mechanisms, which might impact adult cognition, arousal, or reward sensitivity.

  18. Regulation of choline acetyltransferase expression by 17 β-oestradiol in NSC-34 cells and in the spinal cord.

    Science.gov (United States)

    Johann, S; Dahm, M; Kipp, M; Zahn, U; Beyer, C

    2011-09-01

    Motoneurones located in the ventral horn of the spinal cord conciliate cholinergic innervation of skeletal muscles. These neurones appear to be exceedingly affected in neurodegenerative diseases such as amyotrophic lateral sclerosis. The dysfunction of motoneurones is typically accompanied by alterations of cholinergic metabolism and signalling, as demonstrated by a decrease in choline acetyltransferase (ChAT) expression. 17 β-Oestradiol (E(2)) is generally accepted as neuroprotective factor in the brain under acute toxic and neurodegenerative conditions and also appears to exert a protective role for motoneurones. In the present study, we attempted to analyse the role of E(2) signalling on ChAT expression in the motoneurone-like cell line NSC-34 and in vivo. In a first step, we demonstrated the presence of oestrogen receptor α and β in NSC-34 cells, as well as in the cervical and lumbar parts, of the male mouse spinal cord. Subsequently, we investigated the effect of E(2) treatment on ChAT expression. The application of E(2) significantly increased the transcription of ChAT in NSC-34 cells and in the cervical but not lumbar part of the spinal cord. Our results indicate that E(2) can influence the cholinergic system by increasing ChAT expression in the mouse spinal cord. This mechanism might support motoneurones, in addition to survival-promoting mechanisms, in the temporal balance toxic or neurodegenerative challenges. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  19. Human neural stem cells over-expressing choline acetyltransferase restore cognition in rat model of cognitive dysfunction.

    Science.gov (United States)

    Park, Dongsun; Lee, Hong Jun; Joo, Seong Soo; Bae, Dae-Kwon; Yang, Goeun; Yang, Yun-Hui; Lim, Inja; Matsuo, Akinori; Tooyama, Ikuo; Kim, Yun-Bae; Kim, Seung U

    2012-04-01

    A human neural stem cell (NSC) line over-expressing human choline acetyltransferase (ChAT) gene was generated and these F3.ChAT NSCs were transplanted into the brain of rat Alzheimer disease (AD) model which was induced by application of ethylcholine mustard aziridinium ion (AF64A) that specifically denatures cholinergic nerves and thereby leads to memory deficit as a salient feature of AD. Transplantation of F3.ChAT human NSCs fully recovered the learning and memory function of AF64A animals, and induced elevated levels of acetylcholine (ACh) in cerebrospinal fluid (CSF). Transplanted F3.ChAT human NSCs were found to migrate to various brain regions including cerebral cortex, hippocampus, striatum and septum, and differentiated into neurons and astrocytes. The present study demonstrates that brain transplantation of human NSCs over-expressing ChAT ameliorates complex learning and memory deficits in AF64A-cholinotoxin-induced AD rat model. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Pentoxifylline Attenuates Methionine- and Choline-Deficient-Diet-Induced Steatohepatitis by Suppressing TNF-α Expression and Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Min Kyung Chae

    2012-01-01

    Full Text Available Background. Pentoxifylline (PTX anti-TNF properties are known to exert hepatoprotective effects in various liver injury models. The aim of this study was to investigate whether PTX has beneficial roles in the development of methionine- and choline-deficient-(MCD- diet-induced NAFLD SD rats in vivo and TNF-α-induced Hep3B cells in vitro. Methods. SD Rats were classified according to diet (chow or MCD diet and treatment (normal saline or PTX injection over a period of 4 weeks: group I (chow + saline, n=4, group II (chow + PTX, group III (MCD + saline, and group IV (MCD + PTX. Hep3B cells were treated with 100 ng/ml TNF-α (24 h in the absence or presence of PTX (1 mM. Results. PTX attenuated MCD-diet-induced serum ALT levels and hepatic steatosis. In real-time PCR and western blotting analysis, PTX decreased MCD-diet-induced TNF-alpha mRNA expression and proapoptotic unfolded protein response by ER stress (GRP78, p-eIF2, ATF4, IRE1α, CHOP, and p-JNK activation in vivo. PTX (1 mM reduced TNF-α-induced activation of GRP78, p-eIF2, ATF4, IRE1α, and CHOP in vitro. Conclusion. PTX has beneficial roles in the development of MCD-diet-induced steatohepatitis through partial suppression of TNF-α and ER stress.

  1. Choline and Geranate Deep Eutectic Solvent as a Broad-Spectrum Antiseptic Agent for Preventive and Therapeutic Applications.

    Science.gov (United States)

    Zakrewsky, Michael; Banerjee, Amrita; Apte, Sanjana; Kern, Theresa L; Jones, Mattie R; Sesto, Rico E Del; Koppisch, Andrew T; Fox, David T; Mitragotri, Samir

    2016-06-01

    Antiseptic agents are the primary arsenal to disinfect skin and prevent pathogens spreading within the host as well as into the surroundings; however the Food and Drug Administration published a report in 2015 requiring additional validation of nearly all current antiseptic agents before their continued use can be allowed. This vulnerable position calls for urgent identification of novel antiseptic agents. Recently, the ability of a deep eutectic, Choline And Geranate (CAGE), to treat biofilms of Pseudomonas aeruginosa and Salmonella enterica was demonstrated. Here it is reported that CAGE exhibits broad-spectrum antimicrobial activity against a number of drug-resistant bacteria, fungi, and viruses including clinical isolates of Mycobacterium tuberculosis, Staphylococcus aureus, and Candida albicans as well as laboratory strains of Herpes Simplex Virus. Studies in human keratinocytes and mice show that CAGE affords negligible local or systemic toxicity, and an ≈180-14 000-fold improved efficacy/toxicity ratio over currently used antiseptic agents. Further, CAGE penetrates deep into the dermis and treats pathogens located in deep skin layers as confirmed by the ability of CAGE in vivo to treat Propionibacterium acnes infection. In combination, the results clearly demonstrate CAGE holds promise as a transformative platform antiseptic agent for preventive as well as therapeutic applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. A methionine-choline-deficient diet elicits NASH in the immunodeficient mouse featuring a model for hepatic cell transplantation.

    Science.gov (United States)

    Pelz, Sandra; Stock, Peggy; Brückner, Sandra; Christ, Bruno

    2012-02-01

    Non-alcoholic staetohepatitis (NASH) is associated with fat deposition in the liver favoring inflammatory processes and development of fibrosis, cirrhosis and finally hepatocellular cancer. In Western lifestyle countries, NASH has reached a 20% prevalence in the obese population with escalating tendency in the future. Very often, liver transplantation is the only therapeutic option. Recently, transplantation of hepatocyte-like cells differentiated from mesenchymal stem cells was suggested a feasible alternative to whole organ transplantation to ameliorate donor organ shortage. Hence, in the present work an animal model of NASH was established in immunodeficient mice to investigate the feasibility of human stem cell-derived hepatocyte-like cell transplantation. NASH was induced by feeding a methionine/choline-deficient diet (MCD-diet) for up to 5 weeks. Animals developed a fatty liver featuring fibrosis and elevation of the proinflammatory markers serum amyloid A (SAA) and tumor necrosis factor alpha (TNFα). Hepatic triglycerides were significantly increased as well as alanine aminotransferase demonstrating inflammation-linked hepatocyte damage. Elevation of αSMA mRNA and collagen I as well as liver architecture deterioation indicated massive fibrosis. Both short- and long-term post-transplantation human hepatocyte-like cells resided in the mouse host liver indicating parenchymal penetration and most likely functional engraftment. Hence, the NASH model in the immunodeficient mouse is the first to allow for the assessment of the therapeutic impact of human stem cell-derived hepatocyte transplantation. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Silver-choline chloride modified graphene oxide: Novel nano-bioelectrochemical sensor for celecoxib detection and CCD-RSM model.

    Science.gov (United States)

    Parsaee, Zohreh; Karachi, Nima; Abrishamifar, Seyyed Milad; Kahkha, Mohammad Reza Rezaei; Razavi, Razieh

    2018-07-01

    In this study, silver nanoparticles modified choline chloride functionalized graphene oxide (AgNPs-ChCl-GO) was synthesized using sonochemical method and utilized as a bioelectrochemical sensor for detection of celecoxib (CEL). The characterization studies were ultimately performed in order to acheive a more complete understanding of the morphological and structural features of the AgNPs-ChCl-GO using different techniques including FT-IR, AFM, FE-SEM, EDX, and XRD. AgNPs-ChCl-GO demonstrated a significant improvement in the reduction activity of CEL due to the enhancement in the current response compared to the bare carbon paste electrode (CPE). The optimum experimental conditions, were optimized using central composite design (CCD) methodology. The differential pulse voltammetry (DPVs) showed an expanded linear dynamic ranges of 9.6 × 10 -9 -7.4 × 10 -7  M for celecoxib in Britton-Robinson buffer in pH 5.0 with. LOD (S/N = 3) and LOQ (S/N = 10) were obtained 2.51 × 10 -9  M and 6.58 × 10 -9  M respectively. AgNPs-ChCl-GO-carbon paste electrode exhibited suitable properties and high accuracy determination of celecoxib in the human plasma sample. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. The Investigation of Electrochemistry Behaviors of Tyrosinase Based on Directly-Electrodeposited Grapheneon Choline-Gold Nanoparticles.

    Science.gov (United States)

    He, Yaping; Yang, Xiaohui; Han, Quan; Zheng, Jianbin

    2017-06-23

    A novel catechol (CA) biosensor was developed by embedding tyrosinase (Tyr) onto in situ electrochemical reduction graphene (EGR) on choline-functionalized gold nanoparticle (AuNPs-Ch) film. The results of UV-Vis spectra indicated that Tyr retained its original structure in the film, and an electrochemical investigation of the biosensor showed a pair of well-defined, quasi-reversible redox peaks with E pa = -0.0744 V and E pc = -0.114 V (vs. SCE) in 0.1 M, pH 7.0 sodium phosphate-buffered saline at a scan rate of 100 mV/s. The transfer rate constant k s is 0.66 s -1 . The Tyr-EGR/AuNPs-Ch showed a good electrochemical catalytic response for the reduction of CA, with the linear range from 0.2 to 270 μM and a detection limit of 0.1 μM (S/N = 3). The apparent Michaelis-Menten constant was estimated to be 109 μM.

  5. {sup 11}C-Choline PET/CT for restaging prostate cancer. Results from 4,426 scans in a single-centre patient series

    Energy Technology Data Exchange (ETDEWEB)

    Graziani, Tiziano; Ceci, Francesco; Polverari, Giulia; Lima, Giacomo Maria; Lodi, Filippo; Fanti, Stefano [S. Orsola-Malpighi Hospital, University of Bologna, Service of Nuclear Medicine, Bologna (Italy); Castellucci, Paolo [S. Orsola-Malpighi Hospital, University of Bologna, Service of Nuclear Medicine, Bologna (Italy); Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola-Malpighi, UO Medicina Nucleare, Bologna (Italy); Morganti, Alessio Giuseppe [S. Orsola-Malpighi Hospital, University of Bologna, Department of Radiotherapy, Bologna (Italy); Ardizzoni, Andrea [S. Orsola-Malpighi Hospital, University of Bologna, Department of Oncology, Bologna (Italy); Schiavina, Riccardo [S. Orsola-Malpighi Hospital, University of Bologna, Department of Urology, Bologna (Italy)

    2016-10-15

    To evaluate {sup 11}C-choline PET/CT as a diagnostic tool for restaging prostate cancer (PCa), in a large, homogeneous and clinically relevant population of patients with biochemical recurrence (BCR) of PCa after primary therapy. The secondary aim was to assess the best timing for performing {sup 11}C-choline PET/CT during BCR. We retrospectively analysed 9,632 {sup 11}C-choline PET/CT scans performed in our institution for restaging PCa from January 2007 to June 2015. The inclusion criteria were: (1) proven PCa radically treated with radical prostatectomy (RP) or with primary external beam radiotherapy (EBRT); (2) PSA serum values available; (3) proven BCR (PSA >0.2 ng/mL after RP or PSA >2 ng/mL above the nadir after primary EBRT with rising PSA levels). Finally, 3,203 patients with recurrent PCa matching all the inclusion criteria were retrospectively enrolled and 4,426 scans were analysed. Overall, 52.8 % of the {sup 11}C-choline PET/CT scans (2,337/4,426) and 54.8 % of the patients (1,755/3,203) were positive. In 29.4 % of the scans, at least one distant finding was observed. The mean and median PSA values were, respectively, 4.9 and 2.1 ng/mL at the time of the scan (range 0.2 - 50 ng/mL). In our series, 995 scans were performed in patients with PSA levels between 1 and 2 ng/mL. In this subpopulation the positivity rate in the 995 scans was 44.7 %, with an incidence of distant findings of 19.2 % and an incidence of oligometastatic disease (one to three lesions) of 37.7 %. The absolute PSA value at the time of the scan and ongoing androgen deprivation therapy were associated with an increased probability of a positive {sup 11}C-choline PET/CT scan (p < 0.0001). In the ROC analysis, a PSA value of 1.16 ng/mL was the optimal cut-off value. In patients with a PSA value <1.16 ng/mL, 26.8 % of 1,426 {sup 11}C-choline PET/CT scans were positive, with oligometastatic disease in 84.7 % of positive scans. In a large cohort of patients, the feasibility of {sup 11}C-choline

  6. PET/CT with {sup 11}C-choline for evaluation of prostate cancer patients with biochemical recurrence: meta-analysis and critical review of available data

    Energy Technology Data Exchange (ETDEWEB)

    Fanti, Stefano; Castellucci, Paolo [S. Orsola-Malpighi University Hospital, Department of Nuclear Medicine, Bologna (Italy); Minozzi, Silvia [Lazio Regional Health Service, Cochrane Review Group on Drugs and Alcohol, Department of Epidemiology, Rome (Italy); Balduzzi, Sara [University of Modena and Reggio Emilia, Department of Diagnostic Medicine, Clinical and Public Health, Modena (Italy); Herrmann, Ken [David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States); University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Krause, Bernd Joachim [Universitaetsmedizin Rostock, Department of Nuclear Medicine, Rostock (Germany); Oyen, Wim [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Chiti, Arturo [Humanitas Research Hospital, Nuclear Medicine, Rozzano, Milano (Italy); Humanitas University, Rozzano, Milano (Italy)

    2016-01-15

    For the last decade PET and PET/CT with {sup 11}C-choline have been proposed for the evaluation of prostate cancer (PC), but the diagnostic performance of {sup 11}C-choline PET/CT is still a matter of debate. We performed a comprehensive review of the most important clinical application of {sup 11}C-choline PET, restaging of patients with biochemical relapse, following a rigorous methodological approach and including assessment of the risk of bias. We conducted a systematic review and meta-analysis of the literature assessing {sup 11}C-choline PET/CT for its accuracy in the diagnosis and ability to detect the site of recurrence of PC in the restaging of patients with biochemical recurrence after initial treatment with curative intent. We performed a comprehensive literature search of PubMed and the Cochrane Library to determine the accuracy for the detection of the site of recurrence (prostate bed recurrences, metastatic spread to locoregional pelvic lymph nodes or distant metastases). Only studies with a reference standard (for prostatic bed histopathology, for histopathology or biopsy of distant metastases or a composite reference standard with clinical follow-up of at least 12 months, correlative imaging and clinical data) were included. Overall 425 studies were retrieved, of which 43 were judged as potentially relevant and 29 with 2,686 participants were finally included. Of these 29 studies, 18 reported results for any relapse, All 18 studies, with a total of 2,126 participants, reported detection rates. The pooled rate was 62 % (95 % CI 53 - 71 %). Of the 18 studies, 12 with 1,270 participants reported useful data to derive sensitivity and specificity. The pooled sensitivity was 89 % (95 % CI 83 - 93 %) and the pooled specificity was 89 % (95 % CI 73 - 96 %). Of 11 studies reporting results for local relapse, 9 with 993 participants reported detection rates. The pooled rate was 27 % (95 % CI 16 - 38 %). Six studies with 491 participants reported sensitivity

  7. Prospective evaluation of [{sup 11}C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schwarzenboeck, Sarah M.; Krause, Bernd J. [Technical University of Munich, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Rostock University Medical Centre, Department of Nuclear Medicine, Rostock (Germany); Eiber, Matthias; Schwaiger, Markus [Technical University of Munich, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Kundt, Guenther [Rostock University Medical Centre, Department of Biostatistics and Informatics, Rostock (Germany); Retz, Margitta; Treiber, Uwe; Nawroth, Roman; Gschwend, Juergen E.; Thalgott, Mark [Technical University of Munich, Department of Urology, Klinikum rechts der Isar, Munich (Germany); Sakretz, Monique; Kurth, Jens [Rostock University Medical Centre, Department of Nuclear Medicine, Rostock (Germany); Rummeny, Ernst J. [Technical University of Munich, Institute of Radiology, Klinikum rechts der Isar, Munich (Germany)

    2016-11-15

    The aim of this study was to prospectively evaluate the value of [{sup 11}C] Choline PET/CT in monitoring early and late response to a standardized first-line docetaxel chemotherapy in castration refractory prostate cancer (mCRPC) patients. Thirty-two patients were referred for [{sup 11}C] Choline PET/CT before the start of docetaxel chemotherapy, after one and ten chemotherapy cycles (or - in case of discontinuation - after the last administered cycle) for therapy response assessment. [{sup 11}C] Choline uptake (SUV{sub max}, SUV{sub mean}), CT derived Houndsfield units (HU{sub max}, HU{sub mean}), and volume of bone, lung, and nodal metastases and local recurrence were measured semi-automatically at these timepoints. Change in SUV{sub max}, SUV{sub mean}, HU{sub max}, HU{sub mean,} and volume was assessed between PET 2 and 1 (early response assessment, ERA) and PET 3 and 1 (late response assessment, LRA) on a patient and lesion basis. Results of PET/CT were compared to clinically used RECIST 1.1 and clinical criteria based therapy response assessment including PSA for defining progressive disease (PD) and non-progressive disease (nPD), respectively. Relationships between changes of SUV{sub max} and SUV{sub mean} (early and late) and changes of PSA{sub early} and PSA{sub late} were evaluated. Prognostic value of initial SUV{sub max} and SUV{sub mean} was assessed. Statistical analyses were performed using SPSS. In the patient-based ERA and LRA there were no statistically significant differences in change of choline uptake, HU, and volume between PD and nPD applying RECIST or clinical response criteria. In the lesion-based ERA, decrease in choline uptake of bone metastases was even higher in PD (applying RECIST criteria), whereas in LRA the decrease was higher in nPD (applying clinical criteria). There were only significant correlations between change in choline uptake and PSA in ERA in PD, in LRA no significant correlations were discovered. Initial SUV{sub max

  8. Prospective evaluation of [11C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer

    International Nuclear Information System (INIS)

    Schwarzenboeck, Sarah M.; Krause, Bernd J.; Eiber, Matthias; Schwaiger, Markus; Kundt, Guenther; Retz, Margitta; Treiber, Uwe; Nawroth, Roman; Gschwend, Juergen E.; Thalgott, Mark; Sakretz, Monique; Kurth, Jens; Rummeny, Ernst J.

    2016-01-01

    The aim of this study was to prospectively evaluate the value of [ 11 C] Choline PET/CT in monitoring early and late response to a standardized first-line docetaxel chemotherapy in castration refractory prostate cancer (mCRPC) patients. Thirty-two patients were referred for [ 11 C] Choline PET/CT before the start of docetaxel chemotherapy, after one and ten chemotherapy cycles (or - in case of discontinuation - after the last administered cycle) for therapy response assessment. [ 11 C] Choline uptake (SUV max , SUV mean ), CT derived Houndsfield units (HU max , HU mean ), and volume of bone, lung, and nodal metastases and local recurrence were measured semi-automatically at these timepoints. Change in SUV max , SUV mean , HU max , HU mean, and volume was assessed between PET 2 and 1 (early response assessment, ERA) and PET 3 and 1 (late response assessment, LRA) on a patient and lesion basis. Results of PET/CT were compared to clinically used RECIST 1.1 and clinical criteria based therapy response assessment including PSA for defining progressive disease (PD) and non-progressive disease (nPD), respectively. Relationships between changes of SUV max and SUV mean (early and late) and changes of PSA early and PSA late were evaluated. Prognostic value of initial SUV max and SUV mean was assessed. Statistical analyses were performed using SPSS. In the patient-based ERA and LRA there were no statistically significant differences in change of choline uptake, HU, and volume between PD and nPD applying RECIST or clinical response criteria. In the lesion-based ERA, decrease in choline uptake of bone metastases was even higher in PD (applying RECIST criteria), whereas in LRA the decrease was higher in nPD (applying clinical criteria). There were only significant correlations between change in choline uptake and PSA in ERA in PD, in LRA no significant correlations were discovered. Initial SUV max and SUV mean were statistically significantly higher in nPD (applying clinical

  9. Fully automated SPE-based synthesis and purification of 2-[{sup 18}F]fluoroethyl-choline for human use

    Energy Technology Data Exchange (ETDEWEB)

    Schmaljohann, Joern [Department of Nuclear Medicine, University of Bonn, Bonn (Germany); Department of Nuclear Medicine, University of Aachen, Aachen (Germany); Schirrmacher, Esther [McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec (Canada); Waengler, Bjoern; Waengler, Carmen [Department of Nuclear Medicine, Ludwig-Maximilians University, Munich (Germany); Schirrmacher, Ralf, E-mail: ralf.schirrmacher@mcgill.c [McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec (Canada); Guhlke, Stefan, E-mail: stefan.guhlke@ukb.uni-bonn.d [Department of Nuclear Medicine, University of Bonn, Bonn (Germany)

    2011-02-15

    Introduction: 2-[{sup 18}F]Fluoroethyl-choline ([{sup 18}F]FECH) is a promising tracer for the detection of prostate cancer as well as brain tumors with positron emission tomography (PET). [{sup 18}F]FECH is actively transported into mammalian cells, becomes phosphorylated by choline kinase and gets incorporated into the cell membrane after being metabolized to phosphatidylcholine. So far, its synthesis is a two-step procedure involving at least one HPLC purification step. To allow a wider dissemination of this tracer, finding a purification method avoiding HPLC is highly desirable and would result in easier accessibility and more reliable production of [{sup 18}F]FECH. Methods: [{sup 18}F]FECH was synthesized by reaction of 2-bromo-1-[{sup 18}F]fluoroethane ([{sup 18}F]BFE) with dimethylaminoethanol (DMAE) in DMSO. We applied a novel and very reliable work-up procedure for the synthesis of [{sup 18}F]BFE. Based on a combination of three different solid-phase cartridges, the purification of [{sup 18}F]BFE from its precursor 2-bromoethyl-4-nitrobenzenesulfonate (BENos) could be achieved without using HPLC. Following the subsequent reaction of the purified [{sup 18}F]BFE with DMAE, the final product [{sup 18}F]FECH was obtained as a sterile solution by passing the crude reaction mixture through a combination of two CM plus cartridges and a sterile filter. The fully automated synthesis was performed using as well a Raytest SynChrom module (Raytest, Germany) or a Scintomics HotboxIII module (Scintomics, Germany). Results: The radiotracer [{sup 18}F]FECH can be synthesized in reliable radiochemical yields (RCY) of 37{+-}5% (Synchrom module) and 33{+-}5% (Hotbox III unit) in less than 1 h using these two fully automated commercially available synthesis units without HPLC involvement for purification. Detailed quality control of the final injectable [{sup 18}F]FECH solution proved the high radiochemical purity and the absence of Kryptofix2.2.2, DMAE and DMSO used in the

  10. Immunocytochemical localization of choline acetyltransferase and muscarinic ACh receptors in the antenna during development of the sphinx moth Manduca sexta.

    Science.gov (United States)

    Clark, Julie; Meisner, Shannon; Torkkeli, Päivi H

    2005-04-01

    Immunocytochemistry with monoclonal antibodies was used to investigate the locations of muscarinic acetylcholine receptors (mAChR) and choline acetyltransferase (ChAT) in sections of the developing antennae of the moth Manduca sexta. The results were correlated with a previous morphological investigation in the developing antennae which allowed us to locate different cell types at various stages of development. Our findings indicated that the muscarinic cholinergic system was not restricted to the sensory neurons but was also present in glial and epidermal cells. By day 4-5 of adult development, immunoreactivity against both antibodies was present in the axons of the antennal nerve, and more intense labeling was present in sections from older pupae. At days 4-9, the cell bodies of the sensory neurons in the basal part of the epidermis were also intensely immunolabeled by the anti-mAChR antibody. In mature flagella, large numbers of cells, some with processes into hairs, were strongly labeled by both antibodies. Antennal glial cells were intensely immunolabeled with both antibodies by days 4-5, but in later stages, it was not possible to discriminate between glial and neural staining. At days 4-9, we observed a distinctly labeled layer of epidermal cells close to the developing cuticle. The expression of both ChAT and mAChRs by neurons in moth antennae may allow the regulation of excitability by endogenous ACh. Cholinergic communication between neurons and glia may be part of the system that guides axon elongation during development. The cholinergic system in the apical part of the developing epidermis could be involved in cuticle formation.

  11. Magnetic graphene oxide modified with choline chloride-based deep eutectic solvent for the solid-phase extraction of protein.

    Science.gov (United States)

    Huang, Yanhua; Wang, Yuzhi; Pan, Qi; Wang, Ying; Ding, Xueqin; Xu, Kaijia; Li, Na; Wen, Qian

    2015-06-02

    Four kinds of green deep eutectic solvents (DESs) based on choline chloride (ChCl) have been synthesized and coated on the surface of magnetic graphene oxide (Fe3O4@GO) to form Fe3O4@GO-DES for the magnetic solid-phase extraction of protein. X-ray diffraction (XRD), vibrating sample magnetometer (VSM), Fourier transform infrared spectrometry (FTIR), field emission scanning electron microscopy (FESEM) and thermal gravimetric analysis (TGA) were employed to characterize Fe3O4@GO-DES, and the results indicated the successful preparation of Fe3O4@GO-DES. The UV-vis spectrophotometer was used to measure the concentration of protein after extraction. Single factor experiments proved that the extraction amount was influenced by the types of DESs, solution temperature, solution ionic strength, extraction time, protein concentration and the amount of Fe3O4@GO-DES. Comparison of Fe3O4@GO and Fe3O4@GO-DES was carried out by extracting bovine serum albumin, ovalbumin, bovine hemoglobin and lysozyme. The experimental results showed that the proposed Fe3O4@GO-DES performs better than Fe3O4@GO in the extraction of acidic protein. Desorption of protein was carried out by eluting the solid extractant with 0.005 mol L(-1) Na2HPO4 contained 1 mol L(-1) NaCl. The obtained elution efficiency was about 90.9%. Attributed to the convenient magnetic separation, the solid extractant could be easily recycled. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Lower Choline and Myo-Inositol in Temporo-Parietal Cortex Is Associated With Apathy in Amnestic MCI

    Directory of Open Access Journals (Sweden)

    Shankar Tumati

    2018-04-01

    Full Text Available Apathy is a common symptom in patients with amnestic mild cognitive impairment (aMCI and is associated with an increased risk of progression to Alzheimer’s disease (AD. The neural substrates underlying apathy in aMCI may involve multiple brain regions, including the anterior cingulate cortex and the temporo-parietal region. Here we investigated neurometabolites in brain regions that may underlie apathy in aMCI patients using proton magnetic resonance spectroscopy (1H-MRS. Twenty-eight aMCI patients with varying degrees of apathy and 20 matched controls underwent 1H-MRS. Spectra were acquired from single voxels in the posterior cingulate cortex (PCC, dorsal anterior cingulate cortex (DACC, right dorsolateral prefrontal cortex (DLPFC, and right temporo-parietal cortex (TPC. Apathy was measured with the Apathy Evaluation Scale (AES. Spearman partial correlations between metabolite concentrations in each region and severity of apathy were determined. Additionally, analyses of covariance (ANCOVA were performed to determine whether metabolite changes differed between patients with or without clinically-diagnosed apathy. The degree of apathy was found to be negatively correlated with choline and myo-inositol (mI in the TPC. Additional exploratory analyses suggested that N-acetylaspartate (NAA/mI ratio was reduced in aMCI without clinical apathy but not in aMCI with clinical apathy. In the DACC, glutamate and glutamine (Glx levels tended to be higher in the aMCI with apathy group compared to controls and reduced in association with depression scores. In conclusion, apathy in aMCI patients was associated with neurometabolite changes indicative of altered membranal integrity and glial function in the right TPC. Findings also indicated that in a clinically-diagnosed aMCI cohort, apathy symptoms may be suggestive of neural changes that are distinct from aMCI without apathy.

  13. Lower Choline and Myo-Inositol in Temporo-Parietal Cortex Is Associated With Apathy in Amnestic MCI.

    Science.gov (United States)

    Tumati, Shankar; Opmeer, Esther M; Marsman, Jan-Bernard C; Martens, Sander; Reesink, Fransje E; De Deyn, Peter P; Aleman, André

    2018-01-01

    Apathy is a common symptom in patients with amnestic mild cognitive impairment (aMCI) and is associated with an increased risk of progression to Alzheimer's disease (AD). The neural substrates underlying apathy in aMCI may involve multiple brain regions, including the anterior cingulate cortex and the temporo-parietal region. Here we investigated neurometabolites in brain regions that may underlie apathy in aMCI patients using proton magnetic resonance spectroscopy ( 1 H-MRS). Twenty-eight aMCI patients with varying degrees of apathy and 20 matched controls underwent 1 H-MRS. Spectra were acquired from single voxels in the posterior cingulate cortex (PCC), dorsal anterior cingulate cortex (DACC), right dorsolateral prefrontal cortex (DLPFC), and right temporo-parietal cortex (TPC). Apathy was measured with the Apathy Evaluation Scale (AES). Spearman partial correlations between metabolite concentrations in each region and severity of apathy were determined. Additionally, analyses of covariance (ANCOVA) were performed to determine whether metabolite changes differed between patients with or without clinically-diagnosed apathy. The degree of apathy was found to be negatively correlated with choline and myo-inositol (mI) in the TPC. Additional exploratory analyses suggested that N-acetylaspartate (NAA)/mI ratio was reduced in aMCI without clinical apathy but not in aMCI with clinical apathy. In the DACC, glutamate and glutamine (Glx) levels tended to be higher in the aMCI with apathy group compared to controls and reduced in association with depression scores. In conclusion, apathy in aMCI patients was associated with neurometabolite changes indicative of altered membranal integrity and glial function in the right TPC. Findings also indicated that in a clinically-diagnosed aMCI cohort, apathy symptoms may be suggestive of neural changes that are distinct from aMCI without apathy.

  14. Enhanced expression of Nrf2 in mice attenuates the fatty liver produced by a methionine- and choline-deficient diet

    International Nuclear Information System (INIS)

    Zhang, Yu-Kun Jennifer; Yeager, Ronnie L.; Tanaka, Yuji; Klaassen, Curtis D.

    2010-01-01

    Oxidative stress has been proposed as an important promoter of the progression of fatty liver diseases. The current study investigates the potential functions of the Nrf2-Keap1 signaling pathway, an important hepatic oxidative stress sensor, in a rodent fatty liver model. Mice with no (Nrf2-null), normal (wild type, WT), and enhanced (Keap1 knockdown, K1-kd) expression of Nrf2 were fed a methionine- and choline-deficient (MCD) diet or a control diet for 5 days. Compared to WT mice, the MCD diet-caused hepatosteatosis was more severe in the Nrf2-null mice and less in the K1-kd mice. The Nrf2-null mice had lower hepatic glutathione and exhibited more lipid peroxidation, whereas the K1-kd mice had the highest amount of glutathione in the liver and developed the least lipid peroxidation among the three genotypes fed the MCD diet. The Nrf2 signaling pathway was activated by the MCD diet, and the Nrf2-targeted cytoprotective genes Nqo1 and Gstα1/2 were induced in WT and even more in K1-kd mice. In addition, Nrf2-null mice on both control and MCD diets exhibited altered expression profiles of fatty acid metabolism genes, indicating Nrf2 may influence lipid metabolism in liver. For example, mRNA levels of long chain fatty acid translocase CD36 and the endocrine hormone Fgf21 were higher in livers of Nrf2-null mice and lower in the K1-kd mice than WT mice fed the MCD diet. Taken together, these observations indicate that Nrf2 could decelerate the onset of fatty livers caused by the MCD diet by increasing hepatic antioxidant and detoxification capabilities.

  15. Comparison of 11C-choline-PET/CT and whole body-MRI for staging of prostate cancer

    International Nuclear Information System (INIS)

    Eschmann, S.M.; Rieger, A.; Mueller, M.; Bares, R.; Pfannenberg, A.C.; Aschoff, P.; Claussen, C.D.; Schlemmer, H.P.; Paulsen, F.; Anastasiadis, A.

    2007-01-01

    Aim of this study was to compare the diagnostic accuracy of positron emission tomography and computed tomography with 11 C-Choline (Cho-PET/CT) and whole body magneticresonance imaging (WB-MRI) for diagnostic work-up of prostate cancer. Patients, methods: We evaluated retrospectively 42 patients with untreated prostate cancer (n =17), or increasing levels of prostate-specific antigen (PSA) after curative therapy (n = 25) who had been investigated by both Cho-PET/CT and WB-MRI. MRI, CT, and PET images were separately analyzed by experienced radiologists or nuclear medicine experts, followed by consensus reading. Validation was established by histology, follow-up, or consensus reading. Results: 88/103 detected lesions were considered as malignant: 44 bone metastases, 22 local tumor, 15 lymph node metastases, 3 lung, and 3 brain metastases. One further lesion was located in the adrenal gland, which was a second tumor. Overall sensitivity, specificity and accuracy for Cho-PET/CT were 96.6%, 76.5%, and 93.3%, resp., and for WB-MRI 78.4%, 94.1%, and 81.0%, resp. 3 vertebral metastases had initially been missed by Cho-PET/CT and were found retrospectively. MRI identified 2 bone metastases and 1 lymph node metastasis after being informed about the results of Cho-PET/CT. Conclusions: Cho-PET/CT and WB-MRI both presented high accuracy in the detection of bone and lymph node metastases. The strength of MRI is excellent image quality providing detailed anatomical information whereas the advantage of Cho-PET/CT is high image contrast of pathological foci. (orig.)

  16. Molar enthalpy of mixing and refractive indices of choline chloride-based deep eutectic solvents with water

    International Nuclear Information System (INIS)

    Ma, Chunyan; Guo, Yanhua; Li, Dongxue; Zong, Jianpeng; Ji, Xiaoyan; Liu, Chang

    2017-01-01

    Highlights: • Molar enthalpy of mixing and refractive indices for binary mixtures of different deep eutectic solvents with water. • The Redlich–Kister equation and the NRTL model was used to fit the experimental data. • The NRTL model with fitted parameters were used to predict the vapour pressure and compared with experimental data. - Abstract: The molar enthalpies of mixing were measured for binary systems of choline chloride-based deep eutectic solvents (glycerol, ethylene glycol and malonic acid) with water at 298.15 K and 308.15 K, and atmospheric pressure with an isothermal calorimeter. Refractive indices were also measured at 303.15 K and atmospheric pressure. The binary mixtures of {chcl/glycerol (1:2) + water, chcl/ethylene glycol (1:2) + water} showed exothermic behaviour over the entire range of composition, while the binary mixture of {chcl/malonic acid (1:1) + water} showed endothermic behaviour at first and then changed to be exothermic with the increasing content of chcl/malonic acid (1:1). Experimental refractive indices were fitted with the Redlich–Kister equation, and experimental molar enthalpies of mixing were correlated with the Redlich–Kister equation and the non-random two-liquid (NRTL) model. The NRTL model with the fitted parameters was used to predict the vapour pressures of these three mixtures. For mixtures of {chcl/glycerol (1:2) + water} and {chcl/ethylene glycol (1:2) + water}, the predicted vapour pressures agreed well with the experimental results from the literature. While for mixture of {chcl/malonic acid (1:1) + water}, the predicted vapour pressures showed deviation at the high concentration of chcl/malonic acid (1:1), and this was probably because of the complex molecular interaction between chcl/malonic acid (1:1) and water.

  17. Immunohistochemical localization of two types of choline acetyltransferase in neurons and sensory cells of the octopus arm.

    Science.gov (United States)

    Sakaue, Yuko; Bellier, Jean-Pierre; Kimura, Shin; D'Este, Loredana; Takeuchi, Yoshihiro; Kimura, Hiroshi

    2014-01-01

    Cholinergic structures in the arm of the cephalopod Octopus vulgaris were studied by immunohistochemistry using specific antisera for two types (common and peripheral) of acetylcholine synthetic enzyme choline acetyltransferase (ChAT): antiserum raised against the rat common type ChAT (cChAT), which is cross-reactive with molluscan cChAT, and antiserum raised against the rat peripheral type ChAT (pChAT), which has been used to delineate peripheral cholinergic structures in vertebrates, but not previously in invertebrates. Western blot analysis of octopus extracts revealed a single pChAT-positive band, suggesting that pChAT antiserum is cross-reactive with an octopus counterpart of rat pChAT. In immunohistochemistry, only neuronal structures of the octopus arm were stained by cChAT and pChAT antisera, although the pattern of distribution clearly differed between the two antisera. cChAT-positive varicose nerve fibers were observed in both the cerebrobrachial tract and neuropil of the axial nerve cord, while pChAT-positive varicose fibers were detected only in the neuropil of the axial nerve cord. After epitope retrieval, pChAT-positive neuronal cells and their processes became visible in all ganglia of the arm, including the axial and intramuscular nerve cords, and in ganglia of suckers. Moreover, pChAT-positive structures also became detectable in nerve fibers connecting the different ganglia, in smooth nerve fibers among muscle layers and dermal connective tissues, and in sensory cells of the suckers. These results suggest that the octopus arm has two types of cholinergic nerves: cChAT-positive nerves from brain ganglia and pChAT-positive nerves that are intrinsic to the arm.

  18. DSS colitis promotes tumorigenesis and fibrogenesis in a choline-deficient high-fat diet-induced NASH mouse model.

    Science.gov (United States)

    Achiwa, Koichi; Ishigami, Masatoshi; Ishizu, Yoji; Kuzuya, Teiji; Honda, Takashi; Hayashi, Kazuhiko; Hirooka, Yoshiki; Katano, Yoshiaki; Goto, Hidemi

    2016-01-29

    Nonalcoholic steatohepatitis (NASH) patients progress to liver cirrhosis and even hepatocellular carcinoma (HCC). Several lines of evidence indicate that accumulation of lipopolysaccharide (LPS) and disruption of gut microbiota play contributory roles in HCC. Moreover, in a dextran sodium sulfate (DSS)-induced colitis model in mice, a high-fat diet increases portal LPS level and promotes hepatic inflammation and fibrosis. However, this diet-induced NASH model requires at least 50 weeks for carcinogenesis. In this study, we sought to determine whether increased intestinal permeability would aggravate liver inflammation and fibrosis and accelerate tumorigenesis in a diet-induced NASH model. Mice were fed a choline-deficient high-fat (CDHF) diet for 4 or 12 weeks. The DSS group was fed CDHF and intermittently received 1% DSS in the drinking water. Exposure to DSS promoted mucosal changes such as crypt loss and increased the number of inflammatory cells in the colon. In the DSS group, portal LPS levels were elevated at 4 weeks, and the proportions of Clostridium cluster XI in the fecal microbiota were elevated. In addition, levels of serum transaminase, number of lobular inflammatory cells, F4/80 staining-positive area, and levels of inflammatory cytokines were all elevated in the DSS group. Liver histology in the DSS group revealed severe fibrosis at 12 weeks. Liver tumors were detected in the DSS group at 12 weeks, but not in the other groups. Thus, DSS administration promoted liver tumors in a CDHF diet-induced NASH mouse over the short term, suggesting that the induction of intestinal inflammation and gut disruption of microbiota in NASH promote hepatic tumorigenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Radioactive choline uptake in the isolated rat phrenic nerve-hemidiaphragm preparation. A biochemical and autoradiographic study

    Energy Technology Data Exchange (ETDEWEB)

    Veldsema-Currie, R.D.; van Marle, J.; Langemeijer, M.W.; Lind, A.; van Weeren-Kramer, J.

    1984-10-01

    When hemidiaphragms are stimulated via the phrenic nerve in the presence of 10 microM radioactive choline (Ch), the rate of radioactive Ch uptake in the endplate-rich area (EPA) is greater than that in the endplate-poor muscle (M). Ch uptake in the EPA is temperature-dependent, with a Q10 of 2.9 and an activation energy of 19.5 kcal/mol. It is inhibited in a Na+-depleted medium, in the absence of Ca2+, and by 10-20 microM hemicholinium-3 (HC-3) and it is not inhibited by alpha-bungarotoxin even when the muscle is completely paralyzed. In the absence of stimulation the rate of uptake in the EPA is slightly, but not significantly, greater than in M. Using autoradiography, we find an enhanced amount of isotope in the nerve terminals and their immediate vicinities compared with the muscle fibres, in both stimulated and unstimulated hemidiaphragms. There is no enhanced uptake of isotope into the nerve terminals in stimulated tissues in the presence of 26 microM HC-3. The uptake of isotope into the muscle is not altered by any of these treatments. There is a positive correlation between the initial rate of radioactive Ch uptake in the EPA and the amount of isotope in the nerve terminals (the mean corrected grain density above the nerve terminals). Without correcting for the large amount of diffusion that occurs, the ratio of the grain density above the synapses to that above the muscle fibres is 1.66 in tissue stimulated at 1 Hz, 1.04 in stimulated tissues in the presence of 26 microM HC-3, and 1.31 in unstimulated tissues.

  20. Activation of functional α7-containing nAChRs in hippocampal CA1 pyramidal neurons by physiological levels of choline in the presence of PNU-120596.

    Directory of Open Access Journals (Sweden)

    Bopanna I Kalappa

    2010-11-01

    Full Text Available The level of expression of functional α7-containing nicotinic acetylcholine receptors (nAChRs in hippocampal CA1 pyramidal neurons is believed to be very low compared to hippocampal CA1 interneurons, and for many years this expression was largely overlooked. However, high densities of expression of functional α7-containing nAChRs in CA1 pyramidal neurons may not be necessary for triggering important cellular and network functions, especially if activation of α7-containing nAChRs occurs in the presence of positive allosteric modulators such as PNU-120596.An approach previously developed for α7-containing nAChRs expressed in tuberomammillary neurons was applied to investigate functional CA1 pyramidal α7-containing nAChRs using rat coronal hippocampal slices and patch-clamp electrophysiology. The majority (∼71% of tested CA1 pyramidal neurons expressed low densities of functional α7-containing nAChRs as evidenced by small whole-cell responses to choline, a selective endogenous agonist of α7 nAChRs. These responses were potentiated by PNU-120596, a novel positive allosteric modulator of α7 nAChRs. The density of functional α7-containing nAChRs expressed in CA1 pyramidal neurons (and thus, the normalized net effect of activation, i.e., response net charge per unit of membrane capacitance per unit of time was estimated to be ∼5% of the density observed in CA1 interneurons. The results of this study demonstrate that despite low levels of expression of functional pyramidal α7-containing nAChRs, physiological levels of choline (∼10 µM are sufficient to activate these receptors and transiently depolarize and even excite CA1 pyramidal neurons in the presence of PNU-120596. The observed effects are possible because in the presence of 10 µM choline and 1-5 µM PNU-120596, a single opening of an individual pyramidal α7-containing nAChR ion channel appears to transiently depolarize (∼4 mV the entire pyramidal neuron and occasionally

  1. NMR (1H and 13C) based signatures of abnormal choline metabolism in oral squamous cell carcinoma with no prominent Warburg effect

    International Nuclear Information System (INIS)

    Bag, Swarnendu; Banerjee, Deb Ranjan; Basak, Amit; Das, Amit Kumar; Pal, Mousumi; Banerjee, Rita; Paul, Ranjan Rashmi; Chatterjee, Jyotirmoy

    2015-01-01

    At functional levels, besides genes and proteins, changes in metabolome profiles are instructive for a biological system in health and disease including malignancy. It is understood that metabolomic alterations in association with proteomic and transcriptomic aberrations are very fundamental to unravel malignant micro-ambient criticality and oral cancer is no exception. Hence deciphering intricate dimensions of oral cancer metabolism may be contributory both for integrated appreciation of its pathogenesis and to identify any critical but yet unexplored dimension of this malignancy with high mortality rate. Although several methods do exist, NMR provides higher analytical precision in identification of cancer metabolomic signature. Present study explored abnormal signatures in choline metabolism in oral squamous cell carcinoma (OSCC) using 1 H and 13 C NMR analysis of serum. It has demonstrated down-regulation of choline with concomitant up-regulation of its break-down product in the form of trimethylamine N-oxide in OSCC compared to normal counterpart. Further, no significant change in lactate profile in OSCC possibly indicated that well-known Warburg effect was not a prominent phenomenon in such malignancy. Amongst other important metabolites, malonate has shown up-regulation but D-glucose, saturated fatty acids, acetate and threonine did not show any significant change. Analyzing these metabolomic findings present study proposed trimethyl amine N-oxide and malonate as important metabolic signature for oral cancer with no prominent Warburg effect. - Highlights: • NMR ( 1 H and 13 C) study of Oral Squamous cell Carcinoma Serum. • Abnormal Choline metabolomic signatures. • Up-regulation of Trimethylamine N-oxide. • Unchanged lactate profile indicates no prominent Warburg effect. • Proposed alternative glucose metabolism path through up-regulation of malonate

  2. Phospholipids chiral at phosphorus. Dramatic effects of phosphorus chirality on the deuterium NMR properties of the choline head group of phospholipids in the liquid crystalline phase

    International Nuclear Information System (INIS)

    Loffredo, W.M.; Jiang, Rutai; Tsai, Mingdaw

    1990-01-01

    To probe the motional and conformational propertis of the choline head group of 1,2-dipalmitoyl-sn-glycero-3-thiophosphocholine (DPPsC), the R p , S p , and R p + S p isomers of [α-D 2 ]DPPsC, [β-D 2 ]DPPsC, and [δ-D 9 ]DPPsC in the subgel, gel, and liquid crystalline phases were investigated with deuterium NMR, and the results were compared with those of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) labeled at the same positions. In the subgel phase (5 degree C) all isomers of [α-D 2 ]DPPsC and [β-D 2 ]DPPsC displayed amorphous line shapes characteristic of a restricted and disordered motional environment, whereas [δ-D 9 ]DPPsC showed narrower and symmetric line shapes indicating substantial motions. For all three labeled positions the apparent line width of the R p isomer is larger than those of S p and R p + S p isomers, and the amorphous line shape of the R p isomer also persists at 25 and 35 degree C. These results indicate that the motional and conformational properties of the C α -C β segment of DPPsC is very sensitive to the configuration at phosphorus. Structurally, this provides strong support for noncovalent interactions between the quaternary ammonium group of choline and the phosphate group of a neighboring molecule in the bilayers of phosphatidylcholine and suggests that such interactions are important to the motion of the choline chain

  3. Specificity of choline metabolites for in vivo diagnosis of breast cancer using {sup 1}H MRS at 1.5 T

    Energy Technology Data Exchange (ETDEWEB)

    Stanwell, Peter; Gluch, Laurence; Lean, Cynthia; Malycha, Peter; Mountford, Carolyn [Royal North Shore Hospital, Institute for Magnetic Resonance Research and Department of Magnetic Resonance in Medicine, University of Sydney, St Leonards, NSW (Australia); Clark, David [Breast Centre, Waratah, NSW (Australia); Tomanek, Boguslaw [National Research Council Canada, Institute for Biodiagnostics, Winnipeg, MB (Canada); Baker, Luke [Sydney Adventist Hospital, Department of Radiology, Wahroonga, NSW (Australia); Giuffre, Bruno [Royal North Shore Hospital, Department of Radiology, St Leonards, NSW (Australia)

    2005-05-01

    The purpose was to determine if in vivo proton magnetic resonance spectroscopy ({sup 1}H MRS) at 1.5 T can accurately provide the correct pathology of breast disease. Forty-three asymptomatic volunteers including three lactating mothers were examined and compared with 21 breast cancer patients. Examinations were undertaken at 1.5 T using a purpose-built transmit-receive single breast coil. Single voxel spectroscopy was undertaken using echo times of 135 and 350 ms. The broad composite resonance at 3.2 ppm, which includes contributions from choline, phosphocholine (PC), glycerophosphocholine (GPC), myo-inositol and taurine, was found not to be a unique marker for malignancy providing a diagnostic sensitivity and specificity of 80.0 and 86.0%, respectively. This was due to three of the asymptomatic volunteers and all of the lactating mothers also generating the broad composite resonance at 3.2 ppm. Optimised post-acquisitional processing of the spectra resolved a resonance at 3.22 ppm, consistent with PC, in patients with cancer. In contrast the spectra recorded for three false-positive volunteers, and the three lactating mothers had a resonance centred at 3.28 ppm (possibly taurine, myo-inositol or GPC). This improved the specificity of the test to 100%. Careful referencing of the spectra and post-acquisitional processing intended to optimise spectral resolution of in vivo MR proton spectra from human breast tissue resolves the composite choline resonance. This allows the distinction of patients with malignant disease from volunteers with a sensitivity of 80% and specificity of 100%. Therefore, resolution of the composite choline resonance into its constituent components improves the specificity of the in vivo {sup 1}H MRS method, but does not overcome the problem of 20% false-negatives. (orig.)

  4. NMR ({sup 1}H and {sup 13}C) based signatures of abnormal choline metabolism in oral squamous cell carcinoma with no prominent Warburg effect

    Energy Technology Data Exchange (ETDEWEB)

    Bag, Swarnendu, E-mail: Swarna.bag@gmail.com [School of Medical Science and Technology, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Banerjee, Deb Ranjan, E-mail: debranjan2@gmail.com [Department of Chemistry, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Basak, Amit, E-mail: absk@chem.iitkgp.ernet.in [Department of Chemistry, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Das, Amit Kumar, E-mail: amitk@hijli.iitkgp.ernet.in [Department of Biotechnology, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Pal, Mousumi, E-mail: drmpal62@gmail.com [Department of Oral and Maxillofacial Pathology, Guru Nanak Institute of Dental Sciences and Research, Kolkata, West Bengal (India); Banerjee, Rita, E-mail: ritabanerjee@outlook.com [Department of Science and Technology, New Mehrauli Road, New Delhi 110016 (India); Paul, Ranjan Rashmi, E-mail: dr_rsspaul@yahoo.co.in [Department of Oral and Maxillofacial Pathology, Guru Nanak Institute of Dental Sciences and Research, Kolkata, West Bengal (India); Chatterjee, Jyotirmoy, E-mail: jchatterjee.iitkgp@gmail.com [School of Medical Science and Technology, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India)

    2015-04-17

    At functional levels, besides genes and proteins, changes in metabolome profiles are instructive for a biological system in health and disease including malignancy. It is understood that metabolomic alterations in association with proteomic and transcriptomic aberrations are very fundamental to unravel malignant micro-ambient criticality and oral cancer is no exception. Hence deciphering intricate dimensions of oral cancer metabolism may be contributory both for integrated appreciation of its pathogenesis and to identify any critical but yet unexplored dimension of this malignancy with high mortality rate. Although several methods do exist, NMR provides higher analytical precision in identification of cancer metabolomic signature. Present study explored abnormal signatures in choline metabolism in oral squamous cell carcinoma (OSCC) using {sup 1}H and {sup 13}C NMR analysis of serum. It has demonstrated down-regulation of choline with concomitant up-regulation of its break-down product in the form of trimethylamine N-oxide in OSCC compared to normal counterpart. Further, no significant change in lactate profile in OSCC possibly indicated that well-known Warburg effect was not a prominent phenomenon in such malignancy. Amongst other important metabolites, malonate has shown up-regulation but D-glucose, saturated fatty acids, acetate and threonine did not show any significant change. Analyzing these metabolomic findings present study proposed trimethyl amine N-oxide and malonate as important metabolic signature for oral cancer with no prominent Warburg effect. - Highlights: • NMR ({sup 1}H and {sup 13}C) study of Oral Squamous cell Carcinoma Serum. • Abnormal Choline metabolomic signatures. • Up-regulation of Trimethylamine N-oxide. • Unchanged lactate profile indicates no prominent Warburg effect. • Proposed alternative glucose metabolism path through up-regulation of malonate.

  5. Technical note: Evaluation of the uncertainties in (choline+creatine)/citrate ratios measured by proton MR spectroscopic imaging in patients suspicious for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zbyn, S.; Krssak, M.; Memarsadeghi, M.; Gholami, B.; Haitel, A.; Weber, M.; Helbich, T.H.; Trattnig, S.; Moser, E.; Gruber, S.

    2014-07-15

    The presented evaluation of the relative uncertainty (δ'CCC) of the (choline + creatine)/citrate (CC/C) ratios can provide objective information about the quality and diagnostic value of prostate MR spectroscopic imaging data. This information can be combined with the numeric values of CC/C ratios and provides metabolic-quality maps enabling accurate cancer detection and user-independent data evaluation. In addition, the prostate areas suffering most from the low precision of CC/C ratios (e. g., prostate base) were identified.

  6. Detection of lymph node metastasis in patients with nodal prostate cancer relapse using (18)F/(11)C-choline positron emission tomography/computerized tomography.

    Science.gov (United States)

    Jilg, Cordula A; Schultze-Seemann, Wolfgang; Drendel, Vanessa; Vach, Werner; Wieser, Gesche; Krauss, Tobias; Jandausch, Anett; Hölz, Stefanie; Henne, Karl; Reske, Sven N; Grosu, Anca-L; Weber, Wolfgang A; Rischke, H Christian

    2014-07-01

    We evaluated the diagnostic accuracy of choline positron emission tomography/computerized tomography for nodal relapse of prostate cancer according to topographical site and tumor infiltration size in lymph nodes. A total of 72 patients with nodal prostate cancer relapse after primary therapy underwent pelvic and/or retroperitoneal salvage lymph node dissection. Salvage was done after whole body positron emission tomography/computerized tomography with (11)C-choline or (18)F-fluoroethylcholine showed positron emission tomography positive lymph nodes but no other detectable metastasis. Diagnostic accuracy was evaluated in 160 dissected lymph node regions (pelvic left/right and retroperitoneal), 498 subregions (common, external and internal iliac, obturator, presacral, aortic bifurcation, aortal, vena caval and interaortocaval) and 2,122 lymph nodes. Lymph node metastasis was present in 32% of resected lymph nodes (681 of 2,122), resulting in 238 positive subregions and 111 positive regions. Positron emission tomography/computerized tomography was positive for 110 regions and 209 subregions. Sensitivity, specificity, positive and negative predictive values, and accuracy were 91.9%, 83.7%, 92.7%, 82.0% and 89.4% (region based), 80.7%, 93.5%, 91.9%, 84.1% and 87.3% (subregion based), and 57.0%, 98.4%, 94.5%, 82.6% and 84.9% (lesion based), respectively. Of 393 positive lymph node metastases detected by this method 278 (70.7%) were in lymph nodes with a less than 10 mm short axis diameter. Imaging sensitivity was 13.3%, 57.4% and 82.8% for a tumor infiltration depth of 2 or greater to less than 3 mm, 5 or greater to less than 6 mm and 10 or greater to less than 11 mm, respectively. Lymph node metastasis site and the radiotracer ((11)C-choline/(18)F-fluoroethylcholine) had no substantial impact on diagnostic accuracy. Choline positron emission tomography/computerized tomography detects affected lymph node regions (pelvic left/right and retroperitoneal) in patients with

  7. Early time course of N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline in the brain after acute stroke. A proton magnetic resonance spectroscopy study

    DEFF Research Database (Denmark)

    Gideon, P; Henriksen, O; Sperling, B

    1992-01-01

    BACKGROUND AND PURPOSE: The early time course after acute stroke of cerebral N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline was studied in vivo by means of localized water-suppressed proton magnetic resonance spectroscopy. METHODS: Eight patients with acute stroke......, with the loss appearing to occur between 6 and 24 hours after the stroke incident. The reduction in N-acetylaspartate content was greater in the central part than in the peripheral part of the infarcted area. Creatine and phosphocreatine were also reduced in the infarcted area, whereas no significant change...

  8. Supplementation with Folic Acid, but Not Creatine, Increases Plasma Betaine, Decreases Plasma Dimethylglycine, and Prevents a Decrease in Plasma Choline in Arsenic-Exposed Bangladeshi Adults123

    Science.gov (United States)

    Hall, Megan N; Liu, Xinhua; Caudill, Marie A; Malysheva, Olga; Ilievski, Vesna; Lomax-Luu, Angela M; Parvez, Faruque; Siddique, Abu B; Shahriar, Hasan; Uddin, Mohammad N; Islam, Tariqul; Graziano, Joseph H; Gamble, Mary V

    2016-01-01

    Background: Folic acid (FA) supplementation facilitates urinary excretion of arsenic, a human carcinogen. A better understanding of interactions between one-carbon metabolism intermediates may improve the ability to design nutrition interventions that further facilitate arsenic excretion. Objective: The objective was to determine if FA and/or creatine supplementation increase choline and betaine and decrease dimethylglycine (DMG). Methods: We conducted a secondary analysis of the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults (n = 605, aged 24–55 y, 50.3% male) who received arsenic-removal water filters. We examined treatment effects of FA and/or creatine supplementation on plasma choline, betaine, and DMG concentrations, measured by LC–tandem mass spectrometry at baseline and at week 12. Group comparisons were between 1) 400 and 800 μg FA/d (FA400 and FA800, respectively) compared with placebo, 2) creatine (3 g/d) compared with placebo, and 3) creatine plus FA400 compared with FA400. Results: Choline decreased in the placebo group (−6.6%; 95% CI: −10.2%, −2.9%) but did not change in the FA groups (FA400: 2.5%; 95% CI: −0.9%, 6.1%; FA800: 1.4%; 95% CI: −2.5%, 5.5%; P DMG was greater in the FA groups (FA400: −26.7%; 95% CI: −30.9%, −22.2%; FA800: −27.8%; 95% CI: −31.8%, −23.4%) than in the placebo group (−12.3%; 95% CI: −18.1%, −6.2%; P DMG did not differ between creatine treatment arms and their respective reference groups. Conclusion: Supplementation for 12 wk with FA, but not creatine, increases plasma betaine, decreases plasma DMG, and prevents a decrease in plasma choline in arsenic-exposed Bangladeshi adults. This trial was registered at clinicaltrials.gov as NCT01050556. PMID:27052531

  9. Efficient production and purification of functional bacteriorhodopsin with a wheat-germ cell-free system and a combination of Fos-choline and CHAPS detergents.

    Science.gov (United States)

    Genji, Takahisa; Nozawa, Akira; Tozawa, Yuzuru

    2010-10-01

    Cell-free translation is one potential approach to the production of functional transmembrane proteins. We have now examined various detergents as supplements to a wheat-germ cell-free system in order to optimize the production and subsequent purification of a functional model transmembrane protein, bacteriorhodopsin. We found that Fos-choline and CHAPS detergents counteracted each other's inhibitory effects on cell-free translation activity and thereby allowed the efficient production and subsequent purification of functional bacteriorhodopsin in high yield. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. 68Ga-PSMA and 11C-Choline comparison using a tri-modality PET/CT-MRI (3.0 T) system with a dedicated shuttle.

    Science.gov (United States)

    Alonso, Omar; Dos Santos, Gerardo; García Fontes, Margarita; Balter, Henia; Engler, Henry

    2018-01-01

    The aim of this study was to prospectively compare the detection rate of 68 Ga-PSMA versus 11 C-Choline in men with prostate cancer with biochemical recurrence and to demonstrate the added value of a tri-modality PET/CT-MRI system. We analysed 36 patients who underwent both 11 C-Choline PET/CT and 68 Ga-PSMA PET/CT scanning within a time window of 1-2 weeks. Additionally, for the 68 Ga-PSMA scan, we used a PET/CT-MRI (3.0 T) system with a dedicated shuttle, acquiring MRI images of the pelvis. Both scans were positive in 18 patients (50%) and negative in 8 patients (22%). Nine patients were positive with 68 Ga-PSMA alone (25%) and one with 11 C-Choline only (3%). The median detected lesion per patient was 2 for 68 Ga-PSMA (range 0-93) and 1 for 11 C-Choline (range 0-57). Tumour to background ratios in all concordant lesions ( n  = 96) were higher for 68 Ga-PSMA than for 11 C-Choline (110.3 ± 107.8 and 27.5 ± 17.1, mean ± S.D., for each tracer, respectively P  = 0.0001). The number of detected lesions per patient was higher for 11 C-Choline in those with PSA ≥ 3.3 ng/mL, while the number of detected lesions was independent of PSA levels for 68 Ga-PSMA using the same PSA cut-off value. Metastatic pelvic lesions were found in 25 patients (69%) with 68 Ga-PSMA PET/CT, in 18 (50%) with 11 C-Choline PET/CT and in 21 (58%) with MRI (3.0 T). MRI was very useful in detecting recurrence in cases classified as indeterminate by means of PET/CT alone at prostate bed. In patients with prostate cancer with biochemical recurrence 68 Ga-PSMA detected more lesions per patient than 11 C-Choline, regardless of PSA levels. PET/CT-MRI (3.0 T) system is a feasible imaging modality that potentially adds useful relevant information with increased accuracy of diagnosis.

  11. Features of changes in concentration of pituitary thyroid hormone and thyroid hormones in the blood of two-month rats with experimental hypothyroidism before and after operations with N-(2-methoxybenzoyl)-O-isopropyl-α, β-dehydrothyrozine choline ester

    International Nuclear Information System (INIS)

    Khachatryan, T.S.; Topuzyan, V.O.

    2013-01-01

    The features of pituitary thyroid hormone concentration and thyroid hormones in the blood of rats with experimental hypothyroidism before and after injections of N-(2-methoxybenzoyl)-O-isopropyl-α, β-dehydrothyrozine choline ester were investigated. A sharp increase of pituitary thyroid hormone level and a sharp decrease of the level of thyroid hormones in the blood of two-month rats with hypothyroidism have been established. Under the action of N-(2-methoxybenzoyl)-O-isopropyl--α, β-dehydrothyrozine choline ester the decrease of pituitary thyroid hormone concentration and the increase of thyroid hormones level in the rats' blood have been observed and reached their values in intact animals

  12. Expression of human choline kinase in NIH 3T3 fibroblasts increases the mitogenic potential of insulin and insulin-like growth factor I.

    Science.gov (United States)

    Chung, T; Huang, J S; Mukherjee, J J; Crilly, K S; Kiss, Z

    2000-05-01

    In mammalian cells, growth factors, oncogenes, and carcinogens stimulate phosphocholine (PCho) synthesis by choline kinase (CK), suggesting that PCho may regulate cell growth. To validate the role of PCho in mitogenesis, we determined the effects of insulin, insulin-like growth factor I (IGF-I), and other growth factors on DNA synthesis in NIH 3T3 fibroblast sublines highly expressing human choline kinase (CK) without increasing phosphatidylcholine synthesis. In serum-starved CK expressor cells, insulin and IGF-I stimulated DNA synthesis, p70 S6 kinase (p70 S6K) activity, phosphatidylinositol 3-kinase (PI3K) activity, and activating phosphorylation of p42/p44 mitogen-activated protein kinases (MAPK) to greater extents than in the corresponding vector control cells. Furthermore, the CK inhibitor hemicholinium-3 (HC-3) inhibited insulin- and IGF-I-induced DNA synthesis in the CK overexpressors, but not in the vector control cells. The results indicate that high cellular levels of PCho potentiate insulin- and IGF-I-induced DNA synthesis by MAPK- and p70 S6K-regulated mechanisms.

  13. Modeling the Interaction between β-Amyloid Aggregates and Choline Acetyltransferase Activity and Its Relation with Cholinergic Dysfunction through Two-Enzyme/Two-Compartment Model

    Directory of Open Access Journals (Sweden)

    Hedia Fgaier

    2015-01-01

    Full Text Available The effect of β-amyloid aggregates on activity of choline acetyltransferase (ChAT which is responsible for synthesizing acetylcholine (ACh in human brain is investigated through the two-enzyme/two-compartment (2E2C model where the presynaptic neuron is considered as compartment 1 while both the synaptic cleft and the postsynaptic neuron are considered as compartment 2 through suggesting three different kinetic mechanisms for the inhibition effect. It is found that the incorporation of ChAT inhibition by β-amyloid aggregates into the 2E2C model is able to yield dynamic solutions for concentrations of generated β-amyloid, ACh, choline, acetate, and pH in addition to the rates of ACh synthesis and ACh hydrolysis in compartments 1 and 2. It is observed that ChAT activity needs a high concentration of β-amyloid aggregates production rate. It is found that ChAT activity is reduced significantly when neurons are exposed to high levels of β-amyloid aggregates leading to reduction in levels of ACh which is one of the most significant physiological symptoms of AD. Furthermore, the system of ACh neurocycle is dominated by the oscillatory behavior when ChAT enzyme is completely inhibited by β-amyloid. It is observed that the direct inactivation of ChAT by β-amyloid aggregates may be a probable mechanism contributing to the development of AD.

  14. Repeatability of two-dimensional chemical shift imaging multivoxel proton magnetic resonance spectroscopy for measuring human cerebral choline-containing compounds.

    Science.gov (United States)

    Puri, Basant K; Egan, Mary; Wallis, Fintan; Jakeman, Philip

    2018-03-22

    To investigate the repeatability of proton magnetic resonance spectroscopy in the in vivo measurement of human cerebral levels of choline-containing compounds (Cho). Two consecutive scans were carried out in six healthy resting subjects at a magnetic field strength of 1.5 T. On each occasion, neurospectroscopy data were collected from 64 voxels using the same 2D chemical shift imaging (CSI) sequence. The data were analyzed in the same way, using the same software, to obtain the values for each voxel of the ratio of Cho to creatine. The Wilcoxon related-samples signed-rank test, coefficient of variation (CV), repeatability coefficient (RC), and intraclass correlation coefficient (ICC) were used to assess the repeatability. The CV ranged from 2.75% to 33.99%, while the minimum RC was 5.68%. There was excellent reproducibility, as judged by significant ICC values, in 26 voxels. Just three voxels showed significant differences according to the Wilcoxon related-samples signed-rank test. It is therefore concluded that when CSI multivoxel proton neurospectroscopy is used to measure cerebral choline-containing compounds at 1.5 T, the reproducibility is highly acceptable.

  15. Chunggan extract (CGX), methionine-and choline-deficient (MCD) diet-induced hepatosteatosis and oxidative stress in C57BL/6 mice.

    Science.gov (United States)

    Park, H-J; Han, J-M; Kim, H-G; Choi, M-K; Lee, J-S; Lee, H-W; Son, C-G

    2013-12-01

    In the present study, we aimed to evaluate the hepatoprotective and antioxidant effects of Chunggan extract (CGX) in an animal model of hepatosteatosis. The C57BL/6N mice were fed either methionine- and choline-sufficient (MCS) diet (n = 10) or a methionine- and choline-deficient (MCD) diet (n = 50) for 4 weeks, and then they were treated orally with CGX (100 or 200 mg/kg), ursodeoxycholic acid (80 mg/kg, as a positive control), or distilled water (DW, MCS diet group, and MCD diet group) for the final 2 weeks (once per day). The MCD diet induced severe hepatic injury with the typical features of hepatosteatosis in both serum and hepatic tissues. CGX treatment significantly attenuated these alterations in the serum levels including triglyceride (TG), aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin. Moreover, CGX also efficiently prevented from the hepatic TG accumulation in the hepatic tissue, evidenced by histopathological findings, compared with the MCD diet. In addition, CGX treatment significantly ameliorated the excessive oxidative stress and antioxidant markers in the serum as well as the hepatic levels of reactive oxygen species, the levels of malondialdehyde, the protein carbonyl, and total antioxidant capacity, and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. In conclusion, our results indicate the experimental relevance of CGX for potential clinical application in patients with hepatosteatotic disorders and a possible mechanism related to its antioxidant properties.

  16. Rumen-protected methionine compared with rumen-protected choline improves immunometabolic status in dairy cows during the peripartal period.

    Science.gov (United States)

    Zhou, Z; Bulgari, O; Vailati-Riboni, M; Trevisi, E; Ballou, M A; Cardoso, F C; Luchini, D N; Loor, J J

    2016-11-01

    The immunometabolic status of peripartal cows is altered due to changes in liver function, inflammation, and oxidative stress. Nutritional management during this physiological state can affect the biological components of immunometabolism. The objectives of this study were to measure concentrations of biomarkers in plasma, liver tissue, and milk, and also polymorphonuclear leukocyte function to assess the immunometabolic status of cows supplemented with rumen-protected methionine (Met) or choline (CHOL). Forty-eight multiparous Holstein cows were used in a randomized complete block design with 2×2 factorial arrangement of Met (Smartamine M, Adisseo NA, Alpharetta, GA) and CHOL (ReaShure, Balchem Inc., New Hampton, NY) level (with or without). Treatments (12 cows each) were control (CON), no Met or CHOL; CON and Met (SMA); CON and CHOL (REA); and CON and Met and CHOL (MIX). From -50 to -21d before expected calving, all cows received the same diet [1.40Mcal of net energy for lactation (NE L )/kg of DM] with no Met or CHOL. From -21d to calving, cows received the same close-up diet (1.52Mcal of NE L /kg of DM) and were assigned randomly to each treatment. From calving to 30d, cows were on the same postpartal diet (1.71Mcal of NE L /kg of DM) and continued to receive the same treatments until 30d. The Met supplementation was adjusted daily at 0.08% DM of diet, and CHOL was supplemented at 60g/cow per day. Liver (-10, 7, 21, and 30d) and blood (-10, 4, 8, 20, and 30d) samples were harvested for biomarker analyses. Neutrophil and monocyte phagocytosis and oxidative burst were assessed at d 1, 4, 14, and 28d. The Met-supplemented cows tended to have greater plasma paraoxonase. Greater plasma albumin and IL-6 as well as a tendency for lower haptoglobin were detected in Met- but not CHOL-supplemented cows. Similarly, cows fed Met compared with CHOL had greater concentrations of total and reduced glutathione (a potent intracellular antioxidant) in liver tissue. Upon a

  17. Nuclear 82-kDa choline acetyltransferase decreases amyloidogenic APP metabolism in neurons from APP/PS1 transgenic mice.

    Science.gov (United States)

    Albers, Shawn; Inthathirath, Fatima; Gill, Sandeep K; Winick-Ng, Warren; Jaworski, Ewa; Wong, Daisy Y L; Gros, Robert; Rylett, R Jane

    2014-09-01

    Alzheimer disease (AD) is associated with increased amyloidogenic processing of amyloid precursor protein (APP) to β-amyloid peptides (Aβ), cholinergic neuron loss with decreased choline acetyltransferase (ChAT) activity, and cognitive dysfunction. Both 69-kDa ChAT and 82-kDa ChAT are expressed in cholinergic neurons in human brain and spinal cord with 82-kDa ChAT localized predominantly to neuronal nuclei, suggesting potential alternative functional roles for the enzyme. By gene microarray analysis, we found that 82-kDa ChAT-expressing IMR32 neural cells have altered expression of genes involved in diverse cellular functions. Importantly, genes for several proteins that regulate APP processing along amyloidogenic and non-amyloidogenic pathways are differentially expressed in 82-kDa ChAT-containing cells. The predicted net effect based on observed changes in expression patterns of these genes would be decreased amyloidogenic APP processing with decreased Aβ production. This functional outcome was verified experimentally as a significant decrease in BACE1 protein levels and activity and a concomitant reduction in the release of endogenous Aβ1-42 from neurons cultured from brains of AD-model APP/PS1 transgenic mice. The expression of 82-kDa ChAT in neurons increased levels of GGA3, which is involved in trafficking BACE1 to lysosomes for degradation. shRNA-induced decreases in GGA3 protein levels attenuated the 82-kDa ChAT-mediated decreases in BACE1 protein and activity and Aβ1-42 release. Evidence that 82-kDa ChAT can enhance GGA3 gene expression is shown by enhanced GGA3 gene promoter activity in SN56 neural cells expressing this ChAT protein. These studies indicate a novel relationship between cholinergic neurons and APP processing, with 82-kDa ChAT acting as a negative regulator of Aβ production. This decreased formation of Aβ could result in protection for cholinergic neurons, as well as protection of other cells in the vicinity that are sensitive to

  18. Synergistic effects of ginseng stem and leaf-extracted ginsenoside and choline on improving learning and memory in rats Association verification experiment in animals with multiple learning and memory Disorders

    Institute of Scientific and Technical Information of China (English)

    Xiaomin Zhao; Hongxia Gu; Qing Li; Xianglin Xie; Zuoli Xia; Hongxin Cai; Ling Zhang; Dawei Li; Xinnong Wang

    2008-01-01

    BACKGROUND:Ginsenoside extracted from the stem and leaf of ginseng(GSL)and choline have both been shown to improve learning and memory functions; however,further studies are needed to understand the synergistic effects of a combination of both.OBJECTIVE:To verify the combined improved synergistic effects of GSL and choline on learning and memory disorders in rats.DESIGN:Control observation.SETTING:Taishan Medical College.MATERIALS:A total of 150 male Kunming mice weighing(20±2)g and 40 healthy male Wistar rats weighing(220±20)g were provided by the Experimental Animal Department of Jilin University.Animal experimentation received confirmed consent from the local ethic committee.GSL was provided by the Department of Chemistry,Norman Bethune Medical University,and choline was provided by the Third Experiment Factory,Shanghai.METHODS:This study was performed at the Life Science Institute,Taishan Medical College from October 2006 to February 2007.①Scopolamine-induced learning and memory disorders in rats:Forty rats were randomly divided into control group,model group,combination group(400 mg/kg GSL + 200 mg/kg choline),GSL(400 mg/kg)group,and choline(200 mg/kg)group,8 rats/group.Rats were perfused and administrated in the morning,once a day for 14 successive days.Rats in the control group and model group were perfused with 20 mL/kg distilled water and underwent Morris water maze spatial resolution test 1 hour after perfusion on the 10th,11th,and 12th days after administration.Rats also underwent passive step-down avoidance test 1 hour after reperfusion on the 13th and 14th days after administration.Thirty minutes prior to experimentation,rats in the remaining three groups were intraperitoneally(I.p)injected with 2 mg/kg scopolamine,and rats in the control group were I.p.injected with 2 mL/kg saline.②Scopolamine-induced learning disorder and memory acquired disorder in mice:Fifty mice were randomly divided into control group,model group,combination group(400 mg

  19. Exposure of Postnatal Rats to a Static Magnetic Field of 0.14 T Influences Functional Laterality of the Hippocampal High-Affinity Choline Uptake System in Adulthood; In Vitro Test With Magnetic Nanoparticles

    Czech Academy of Sciences Publication Activity Database

    Krištofíková, Z.; Čermák, M.; Benešová, O.; Klaschka, Jan; Zach, P.

    2005-01-01

    Roč. 30, č. 2 (2005), s. 253-262 ISSN 0364-3190 R&D Projects: GA MZd NF7576 Keywords : magnetic nanoparticles * choline transport * cholinergic * functional impairment * hippocampus * laterality * magnetoreception * static magnetic field Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.187, year: 2005

  20. Choline Intake, Plasma Riboflavin, and the Phosphatidylethanolamine N-Methyltransferase G5465A Genotype Predict Plasma Homocysteine in Folate-Deplete Mexican-American Men with the Methylenetetrahydrofolate Reductase 677TT Genotype

    NARCIS (Netherlands)

    Caudill, M.A.; Dellschaft, N.; Solis, C.; Hinkis, S.; Ivanov, A.A.; Nash-Barboza, S.; Randall, K.E.; Jackson, B.; Solomita, G.N.; Vermeylen, F.

    2009-01-01

    We previously showed that provision of the folate recommended dietary allowance and either 300, 550, 1100, or 2200 mg/d choline for 12 wk resulted in diminished folate status and a tripling of plasma total homocysteine (tHcy) in men with the methylenetetrahydrofolate reductase (MTHFR) 677TT

  1. MTHFR deficiency or reduced intake of folate or choline in pregnant mice results in impaired short-term memory and increased apoptosis in the hippocampus of wild-type offspring.

    Science.gov (United States)

    Jadavji, N M; Deng, L; Malysheva, O; Caudill, M A; Rozen, R

    2015-08-06

    Genetic or nutritional disturbances in one-carbon metabolism, with associated hyperhomocysteinemia, can result in complex disorders including pregnancy complications and neuropsychiatric diseases. In earlier work, we showed that mice with a complete deficiency of methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate and homocysteine metabolism, had cognitive impairment with disturbances in choline metabolism. Maternal demands for folate and choline are increased during pregnancy and deficiencies of these nutrients result in several negative outcomes including increased resorption and delayed development. The goal of this study was to investigate the behavioral and neurobiological impact of a maternal genetic deficiency in MTHFR or maternal nutritional deficiency of folate or choline during pregnancy on 3-week-old Mthfr(+/+) offspring. Mthfr(+/+) and Mthfr(+/-) females were placed on control diets (CD); and Mthfr(+/+) females were placed on folate-deficient diets (FD) or choline-deficient diets (ChDD) throughout pregnancy and lactation until their offspring were 3weeks of age. Short-term memory was assessed in offspring, and hippocampal tissue was evaluated for morphological changes, apoptosis, proliferation and choline metabolism. Maternal MTHFR deficiency resulted in short-term memory impairment in offspring. These dams had elevated levels of plasma homocysteine when compared with wild-type dams. There were no differences in plasma homocysteine in offspring. Increased apoptosis and proliferation was observed in the hippocampus of offspring from Mthfr(+/-) mothers. In the maternal FD and ChDD study, offspring also showed short-term memory impairment with increased apoptosis in the hippocampus; increased neurogenesis was observed in ChDD offspring. Choline acetyltransferase protein was increased in the offspring hippocampus of both dietary groups and betaine was decreased in the hippocampus of FD offspring. Our results reveal short-term memory

  2. Supplementation with rumen-protected methionine or choline during the transition period influences whole-blood immune response in periparturient dairy cows.

    Science.gov (United States)

    Vailati-Riboni, M; Zhou, Z; Jacometo, C B; Minuti, A; Trevisi, E; Luchini, D N; Loor, J J

    2017-05-01

    Methionine, together with Lys, is the most limiting AA for milk production in dairy cows. Besides its crucial role in milk production, Met and its derivate metabolites (e.g., glutathione, taurine, polyamines) are well-known immunonutrients in nonruminants, helping support and boost immune function and activity. In the present study, the effects of Met or choline, as its precursor, were investigated using an ex vivo whole blood challenge. The study involved 33 multiparous Holstein cows (from a larger cohort with a factorial arrangement of treatments) assigned from d -21 to +30 relative to parturition to a basal control (CON) diet, CON plus rumen-protected Met (MET, Smartamine M, Adisseo NA, Alpharetta, GA) at a rate of 0.08% of dry matter, or CON plus rumen-protected choline (CHOL, ReaShure, Balchem Inc., New Hampton, NY) at 60 g/d. Blood was sampled on d -15, -7, 2, 7, and 20 for ex vivo lipopolysaccharide (LPS) challenge, and on d 1, 4, 14, and 28 relative to parturition for phagocytosis and oxidative burst assays. The MET cows had greater energy-corrected milk production and milk protein content. Overall, IL-6 response to LPS increased around parturition, whereas IL-1β remained constant, casting doubt on the existence of systemic immunosuppression in the peripartal period. Supplementation with MET dampened the postpartal blood response to LPS (lower IL-1β), while improving postpartum neutrophil and monocyte phagocytosis capacity and oxidative burst activity. In contrast, CHOL supplementation increased monocyte phagocytosis capacity. Overall, the data revealed a peripartal immune hyper-response, which appeared to have been mitigated by MET supplementation. Both MET and CHOL effectively improved immune function; however, MET affected the immune and antioxidant status before parturition, which might have been beneficial to prepare the cow to respond to metabolic challenges after parturition. These results provide insights on potential differences in the

  3. Better postpartal performance in dairy cows supplemented with rumen-protected methionine compared with choline during the peripartal period.

    Science.gov (United States)

    Zhou, Z; Vailati-Riboni, M; Trevisi, E; Drackley, J K; Luchini, D N; Loor, J J

    2016-11-01

    The onset of lactation in dairy cows is characterized by high output of methylated compounds in milk when sources of methyl group are in short supply. Methionine and choline (CHOL) are key methyl donors and their availability during this time may be limiting for milk production, hepatic lipid metabolism, and immune function. Supplementing rumen-protected Met and CHOL may improve overall performance and health of transition cows. The objective of this study was to evaluate the effect of supplemental rumen-protected Met and CHOL on performance and health of transition cows. Eighty-one multiparous Holstein cows were used in a randomized, complete, unbalanced block design with 2×2 factorial arrangement of Met (Smartamine M, Adisseo NA, Alpharetta, GA) and CHOL (ReaShure, Balchem Inc., New Hampton, NY) inclusion (with or without). Treatments (20 to 21 cows each) were control (CON), CON+Met (SMA), CON+CHOL (REA), and CON+Met+CHOL (MIX). From -50 to -21d before expected calving, all cows received the same diet (1.40Mcal of NE L /kg of DM) with no Met or CHOL. From -21d to calving, cows received the same close-up diet (1.52Mcal of NE L /kg of DM) and were assigned randomly to treatments (CON, SMA, REA, or MIX) supplied as top dresses. From calving to 30 DIM, cows were fed the same postpartal diet (1.71Mcal of NE L /kg of DM) and continued to receive the same treatments through 30 DIM. The Met supplementation was adjusted daily at 0.08% DM of diet and REA was supplemented at 60g/d. Incidence of clinical ketosis and retained placenta tended to be lower in Met-supplemented cows. Supplementation of Met (SMA, MIX) led to greater DMI compared with other treatments (CON, REA) in both close-up (14.3 vs. 13.2kg/d, SEM 0.3) and first 30d postpartum (19.2 vs. 17.2kg/d, SEM 0.6). Cows supplemented with Met (SMA, MIX) had greater yields of milk (44.2 vs. 40.4kg/d, SEM 1.2), ECM (44.6 vs. 40.5kg/d, SEM 1.0), and FCM (44.6 vs. 40.8kg/d, SEM 1.0) compared with other (CON, REA) treatments

  4. Is the detection rate of 18F-choline PET/CT influenced by androgen-deprivation therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Chondrogiannis, Sotirios; Marzola, Maria Cristina; Grassetto, Gaia; Maffione, Anna Margherita; Rampin, Lucia; Rubello, Domenico [' ' Santa Maria della Misericordia' ' Hospital, Rovigo (Italy). PET/CT Centre; Ferretti, Alice [' ' San Giacomo Apostolo' ' Hospital, Castelfranco Veneto, Treviso (Italy). Service of Medical Physics; Fanti, Stefano [Azienda Ospedaliero-Univ. Policlinico S. Orsola-Malpighi, Bologna (Italy). Dept. of Nuclear Medicine; Giammarile, Francesco [Lyon 1 Univ. Centre Hospitalier Lyon Sud Biophysique, Villeurbanne (Italy). Dept. of Nuclear Medicine

    2014-07-15

    To evaluate if the detection rate (DR) of {sup 18}F-choline (18F-CH) PET/CT is influenced by androgen-deprivation therapy (ADT) in patients with prostate cancer (PC) already treated with radical intent and presenting biochemical relapse. We have retrospectively evaluated {sup 18}F-CH PET/CT scans of 325 consecutive PC patients enrolled in the period November 2009 to December 2012 previously treated with radical intent and referred to our centre to perform {sup 18}F-CH PET/CT for biochemical relapse. Two different groups of patients were evaluated. group A included the whole sample of 325 patients (mean age 70 years, range: 49-86) who presented trigger PSA between 0.1 and 80 ng/ml (mean 5.5 ng/ml), and group B included 187 patients (mean age 70 years, range 49-86) with medium-low levels of trigger PSA ranging between 0.5 and 5 ng/ml (mean PSA 2.1 ng/ml); group B was chosen in order to obtain a more homogeneous group of patients in terms of PSA values also excluding both very low and very high PSA levels avoiding the ''a priori'' higher probability of negative or positive PET scan, respectively. At the time of examination, 139 patients from group A and 72 patients from group B were under ADT: these patients were considered to be hormone-resistant PC patients because from their oncologic history (>18 months) an increase of PSA levels emerged despite the ongoing ADT. The relationship between {sup 18}F-CH PET/CT findings and possible clinical predictors was investigated using both univariate and multivariate binary logistic regression analyses, including trigger PSA and ADT. Considering the whole population, overall DR of {sup 18}F-CH PET was 58.2 % (189/325 patients). In the whole sample of patients (group A), both at the univariate and multivariate logistic regression analysis, trigger PSA and ADT were significantly correlated with the DR of {sup 18}F-CH PET (p < 0.05). Moreover, the DR in patients under ADT (mean PSA 7.8 ng/ml) was higher than in

  5. Is the detection rate of 18F-choline PET/CT influenced by androgen-deprivation therapy?

    International Nuclear Information System (INIS)

    Chondrogiannis, Sotirios; Marzola, Maria Cristina; Grassetto, Gaia; Maffione, Anna Margherita; Rampin, Lucia; Rubello, Domenico; Ferretti, Alice; Fanti, Stefano; Giammarile, Francesco

    2014-01-01

    To evaluate if the detection rate (DR) of 18 F-choline (18F-CH) PET/CT is influenced by androgen-deprivation therapy (ADT) in patients with prostate cancer (PC) already treated with radical intent and presenting biochemical relapse. We have retrospectively evaluated 18 F-CH PET/CT scans of 325 consecutive PC patients enrolled in the period November 2009 to December 2012 previously treated with radical intent and referred to our centre to perform 18 F-CH PET/CT for biochemical relapse. Two different groups of patients were evaluated. group A included the whole sample of 325 patients (mean age 70 years, range: 49-86) who presented trigger PSA between 0.1 and 80 ng/ml (mean 5.5 ng/ml), and group B included 187 patients (mean age 70 years, range 49-86) with medium-low levels of trigger PSA ranging between 0.5 and 5 ng/ml (mean PSA 2.1 ng/ml); group B was chosen in order to obtain a more homogeneous group of patients in terms of PSA values also excluding both very low and very high PSA levels avoiding the ''a priori'' higher probability of negative or positive PET scan, respectively. At the time of examination, 139 patients from group A and 72 patients from group B were under ADT: these patients were considered to be hormone-resistant PC patients because from their oncologic history (>18 months) an increase of PSA levels emerged despite the ongoing ADT. The relationship between 18 F-CH PET/CT findings and possible clinical predictors was investigated using both univariate and multivariate binary logistic regression analyses, including trigger PSA and ADT. Considering the whole population, overall DR of 18 F-CH PET was 58.2 % (189/325 patients). In the whole sample of patients (group A), both at the univariate and multivariate logistic regression analysis, trigger PSA and ADT were significantly correlated with the DR of 18 F-CH PET (p 18 F-CH PET and ADT. In group B patients only trigger PSA resulted a reliable predictor of the 18 F-CH positivity, since ADT was not

  6. The effect of dietary supplementation with rumen-protected methionine alone or in combination with rumen-protected choline and betaine on sheep milk and antioxidant capacity.

    Science.gov (United States)

    Tsiplakou, E; Mavrommatis, A; Kalogeropoulos, T; Chatzikonstantinou, M; Koutsouli, P; Sotirakoglou, K; Labrou, N; Zervas, G

    2017-10-01

    This study investigated the effects of dietary inclusion of rumen-protected methionine alone or in combination with rumen-protected choline and betaine on: (i) milk yield, chemical composition and fatty acids (FA) profile and (ii) blood plasma glutathione transferase (GST) activity of periparturient ewes. Furthermore, the oxidative stress indicators for measuring total antioxidant and free radical scavenging activity [ferric reducing ability of plasma (FRAP) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays] were also determined in plasma and milk of ewes. Thus, 45 ewes were divided into three equal groups. Each animal of the control group fed daily with a basal diet. The same diet was offered also in each animal of the other two groups. However, the concentrate fed to M group was supplemented with 2.5 g/kg rumen-protected methionine, while the concentrate fed to MCB group with 5 g/kg of a commercial product which contained a combination of methionine, choline and betaine, all three in rumen-protected form. The results showed that the M diet, compared with the control, increased significantly the ewe's milk fat and the total solids content. Likewise, a tendency for higher milk fat and total solids content in ewes fed the MCB diet was also observed. Both M and MCB diets had not noticeable impact on ewes milk FA profile. Significantly higher FRAP values in the blood plasma of ewes fed the MCB and in the milk of ewes fed with the M diet compared with the control were found. Additionally, significantly higher GST activity in the blood plasma of ewes fed the M diet, compared with the control, was observed. Moreover, a significant increase (by 20%) and a tendency for increase (by 16.72%) in the growth rate of lambs nursing ewes fed with M and MCB diets, respectively, compared to controls, were found. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

  7. Branched-chain amino acids alleviate hepatic steatosis and liver injury in choline-deficient high-fat diet induced NASH mice.

    Science.gov (United States)

    Honda, Takashi; Ishigami, Masatoshi; Luo, Fangqiong; Lingyun, Ma; Ishizu, Yoji; Kuzuya, Teiji; Hayashi, Kazuhiko; Nakano, Isao; Ishikawa, Tetsuya; Feng, Guo-Gang; Katano, Yoshiaki; Kohama, Tomoya; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Goto, Hidemi; Hirooka, Yoshiki

    2017-04-01

    For successful treatment for nonalcoholic steatohepatitis (NASH), it may be important to treat the individual causative factors. At present, however, there is no established treatment for this disease. Branched-chain amino acids (BCAAs) have been used to treat patients with decompensated cirrhosis. In order to elucidate the mechanisms responsible for the effects of BCAAs on hepatic steatosis and disease progression, we investigated the effects of BCAA supplementation in mice fed a choline-deficient high-fat diet (CDHF), which induces NASH. Male mice were divided into four groups that received (1) choline-sufficient high fat (HF) diet (HF-control), (2) HF plus 2% BCAA in drinking water (HF-BCAA), (3) CDHF diet (CDHF-control), or (4) CDHF-BCAA for 8weeks. We monitored liver injury, hepatic steatosis and cholesterol, gene expression related to lipid metabolism, and hepatic fat accumulation. Serum alanine aminotransferase (ALT) levels and hepatic triglyceride (TG) were significantly elevated in CDHF-control relative to HF-control. Liver histopathology revealed severe steatosis, inflammation, and pericellular fibrosis in CDHF-control, confirming the NASH findings. Serum ALT levels and hepatic TG and lipid droplet areas were significantly lower in CDHF-BCAA than in CDHF-control. Gene expression and protein level of fatty acid synthase (FAS), which catalyzes the final step in fatty acid biosynthesis, was significantly decreased in CDHF-BCAA than in CDHF-control (PBCAA was significantly lower than those of CDHF-control. BCAA can alleviate hepatic steatosis and liver injury associated with NASH by suppressing FAS gene expression and protein levels. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome.

    Science.gov (United States)

    Smits, Loek P; Kootte, Ruud S; Levin, Evgeni; Prodan, Andrei; Fuentes, Susana; Zoetendal, Erwin G; Wang, Zeneng; Levison, Bruce S; Cleophas, Maartje C P; Kemper, E Marleen; Dallinga-Thie, Geesje M; Groen, Albert K; Joosten, Leo A B; Netea, Mihai G; Stroes, Erik S G; de Vos, Willem M; Hazen, Stanley L; Nieuwdorp, Max

    2018-03-26

    Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge. We performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d 6 -choline and d 3 -carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250 mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18 F-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18 F-fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells. Single lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation. URL: http://www.trialregister.nl. Unique identifier: NTR 4338. © 2018 The Authors. Published on

  9. Quantitative evaluation of bone metastases from prostate cancer with simultaneous [18F] choline PET/MRI. Combined SUV and ADC analysis

    International Nuclear Information System (INIS)

    Wetter, A.; Lipponer, C.; Nensa, F.; Schlosser, T.W.; Lauenstein, T.C.; Heusch, P.; Ruebben, H.; Poeppel, T.D.; Nagarajah, J.

    2014-01-01

    To quantitatively analyze bone metastases from prostate cancer and correlate the apparent diffusion coefficients (ADCs) and standardized uptake values (SUVs). Fifty-five patients with biopsy-proven prostate cancer or suspected recurrent prostate cancer were examined with simultaneous [ 18 F] choline Positron emission tomography (PET)/MRI at 3 T. In 11 patients, thirty-two PET-positive bone lesions could be identified that were located in the field-of-view of the Diffusion weighted imaging-sequence. Region-of-interest and volume-of-interest analyses were performed to measure the mean and minimal ADCs and to assess maximum and mean SUVs of every bone lesion. Correlations between maximum and mean SUVs and mean and minimal ADCs were calculated. The SUV max of all lesions was 5.5 ± 3.1 (mean ± SD). The SUV mean was 1.8 ± 0.9. The mean ADC (ADC mean ) of all lesions was 0.67 ± 0.13 x 10 -3 mm 2 /s. The minimal ADC (ADC min ) of all lesions was 0.56 ± 0.14 x 10 -3 mm 2 /s. There was a moderate but significant inverse correlation of SUV max vs. ADC mean with a correlation coefficient of -0.4 (p=0.02). There was also a significant inverse correlation of SUV max vs. ADC min with r=-0.41 (p=0.02). Our initial results demonstrate a moderate but significant inverse correlation between increased choline metabolism and ADC values of bone metastases from prostate cancer. Further research on a multimodality approach using simultaneous PET/MRI in bone metastasis of prostate cancer seems to be justified. (author)

  10. A method comparison of a food frequency questionnaire to measure folate, choline, betaine, vitamin C and carotenoids with 24-h dietary recalls in women of reproductive age.

    Science.gov (United States)

    Coathup, V; Wheeler, S; Smith, L

    2016-03-01

    The objective of this study was to conduct a method comparison of a modified food frequency questionnaire (FFQ), designed to estimate usual dietary intake of selected micronutrients and antioxidants including folate, choline, betaine, vitamin C and carotenoids (α-carotene, β-carotene, lutein, lycopene and β-cryptoxanthin) with 24-h dietary recalls (24-HR) in women of reproductive age. Sixty-four British women of reproductive age (18-40 years) were recruited in Oxford, UK and provided complete dietary data for analysis. We compared micronutrient estimates from the FFQ against estimates derived from three multiple-pass, 24-HR interviews, by evaluating Pearson's correlation coefficients and Bland-Altman plots. Median intakes of most nutrients were higher when measured by FFQ compared with 24-HR. Strong correlation coefficients were observed for folate (r=0.80) and choline (r=0.68), whereas moderate correlation coefficients were observed for vitamin C (0.50) and lycopene (0.43). Weak correlation coefficients were observed for betaine (0.39) and other carotenoids (r=0.26-0.38). Bland-Altman plots indicated that there was a large amount of variability in the FFQ estimates of nutrient intakes compared to those using 24-HR, particularly for carotenoids. The findings indicate that this FFQ estimated higher mean intakes for most nutrients. Pearson's correlation coefficients were comparable with previous research; however, the Bland-Altman plots suggest a high variability in mean nutrient estimates between the FFQ and 24-h. We recommend further investigation of the validity of this FFQ before use.

  11. Differential co-localization with choline acetyltransferase in nervus terminalis suggests functional differences for GnRH isoforms in bonnethead sharks (Sphyrna tiburo).

    Science.gov (United States)

    Moeller, John F; Meredith, Michael

    2010-12-17

    The nervus terminalis (NT) is a vertebrate cranial nerve whose function in adults is unknown. In bonnethead sharks, the nerve is anatomically independent of the olfactory system, with two major cell populations within one or more ganglia along its exposed length. Most cells are immunoreactive for either gonadotropin-releasing hormone (GnRH) or RF-amide-like peptides. To define further the cell populations and connectivity, we used double-label immunocytochemistry with antisera to different isoforms of GnRH and to choline acetyltransferase (ChAT). The labeling patterns of two GnRH antisera revealed different populations of GnRH-immunoreactive (ir) cell profiles in the NT ganglion. One antiserum labeled a large group of cells and fibers, which likely contain mammalian GnRH (GnRH-I) as described in previous studies and which were ChAT immunoreactive. The other antiserum labeled large club-like structures, which were anuclear, and a sparse number of fibers, but with no clear labeling of cell bodies in the ganglion. These club structures were choline acetyltrasferase (ChAT)-negative, and preabsorption control tests suggest they may contain chicken-GnRH-II (GnRH-II) or dogfish GnRH. The second major NT ganglion cell-type was immunoreactive for RF-amides, which regulate GnRH release in other vertebrates, and may provide an intraganglionic influence on GnRH release. The immunocytochemical and anatomical differences between the two GnRH-immunoreactive profile types indicate possible functional differences for these isoforms in the NT. The club-like structures may be sites of GnRH release into the general circulation since these structures were observed near blood vessels and resembled structures seen in the median eminence of rats. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Development of a chemically defined platform fed-batch culture media for monoclonal antibody-producing CHO cell lines with optimized choline content.

    Science.gov (United States)

    Kuwae, Shinobu; Miyakawa, Ichiko; Doi, Tomohiro

    2018-01-11

    A chemically defined platform basal medium and feed media were developed using a single Chinese hamster ovary (CHO) cell line that produces a monoclonal antibody (mAb). Cell line A, which showed a peak viable cell density of 5.9 × 10 6  cells/mL and a final mAb titer of 0.5 g/L in batch culture, was selected for the platform media development. Stoichiometrically balanced feed media were developed using glucose as an indicator of cell metabolism to determine the feed rates of all other nutrients. A fed-batch culture of cell line A using the platform fed-batch medium yielded a 6.4 g/L mAb titer, which was 12-fold higher than that of the batch culture. To examine the applicability of the platform basal medium and feed media, three other cell lines (A16, B, and C) that produce mAbs were cultured using the platform fed-batch medium, and they yielded mAb titers of 8.4, 3.3, and 6.2 g/L, respectively. The peak viable cell densities of the three cell lines ranged from 1.3 × 10 7 to 1.8 × 10 7  cells/mL. These results show that the nutritionally balanced fed-batch medium and feeds worked well for other cell lines. During the medium development, we found that choline limitation caused a lower cell viability, a lower mAb titer, a higher mAb aggregate content, and a higher mannose-5 content. The optimal choline chloride to glucose ratio for the CHO cell fed-batch culture was determined. Our platform basal medium and feed media will shorten the medium-development time for mAb-producing cell lines.

  13. Evaluation of tumor recurrences after radical prostatectomy using 18F-Choline PET/CT and 3T multiparametric MRI without endorectal coil: a single center experience.

    Science.gov (United States)

    Couñago, Felipe; Recio, Manuel; Maldonado, Antonio; Del Cerro, Elia; Díaz-Gavela, Ana Aurora; Thuissard, Israel J; Sanz-Rosa, David; Marcos, Francisco José; Olaciregui, Karmele; Mateo, María; Cerezo, Laura

    2016-12-07

    To evaluate and compare the utility of 18F-fluorocholine (18F-CH) PET/CT versus 3-Tesla multiparametric MRI (mpMRI) without endorectal coil to detect tumor recurrences in patients with biochemical relapse following radical prostatectomy (RP). Secondarily, to identify possible prognostic variables associated with mpMRI and 18F-CH PET/CT findings. Retrospective study of 38 patients who developed biochemical recurrence after RP between the years 2011 and 2015 at our institution. PET/CT and mpMRI were both performed within 30 days of each other in all patients. The PET/CT was reviewed by a nuclear medicine specialist while the mpMRI was assessed by a radiologist, both of whom were blinded to outcomes. The median prostate-specific antigen (PSA) value pre-MRI/PET-CT was 0.9 ng/mL (interquartile range 0.4-2.2 ng/mL). There were no differences in the detection rate between 18F-CH PET/CT and mpMRI for local recurrence (LR), lymph node recurrence (LNR) and bone metastases (BM). Separately, mpMRI and 18F-CH PET/CT were positive for recurrence in 55.2% and 52.6% of cases, respectively, and in 65.7% of cases when findings from both modalities were considered together. The detection of LR was better with combined mpMRI and choline PET/CT versus choline PET/CT alone (34.2% vs 18.4%, p = 0.04). Salvage treatment was modified in 22 patients (57.8%) based on the imaging findings. PSA values on the day of biochemical failure were significantly associated with mpMRI positivity (adjusted odds ratio (OR): 30.9; 95% confidence interval (CI): 1.5-635.8). Gleason score > 7 was significantly associated with PET/CT positivity (OR: 13.9; 95% CI: 1.5-125.6). A significant association was found between PSA doubling time (PSADT) (OR: 1.3; 95% CI: 1.0-1.7), T stage (OR: 21.1; 95% CI: 1.6-272.1), and LR. Multiparametric MRI and 18F-CH PET/CT yield similar detection rates for LR, LNR and pelvic BM. The combination of both imaging techniques provides a better LR detection versus choline

  14. Effect of adding different levels of rumen protected choline to the diet on productive and reproductive performance of female goats and growth of their kids from birthing to weaning.

    Science.gov (United States)

    Habeeb, Alsaied A; Gad, Ahmed E; Atta, Mostafa A; Mustafa, Mohammed M

    2018-02-01

    Forty female goats in the third parity were randomly divided into four similar groups. The experiment was started 20 days before mating and lasted until the end of the suckling period for 60 days and weaning their kids. The first group were fed diet without supplementation and kept as control while in the second, third and fourth groups, each doe was fed diets with rumen protected choline (RPC) at the rate of 10, 20 and 40 g/day, respectively. Results showed that number of doe kidding twins and triplets and litter weight of kids born per group increased with increasing the level of RPC in the diet of goats and viability rate of born kids during the suckling period improved due to RPC supplementation in the diets of their mothers. Duration of estrous, days from weaning to estrous, days from kidding to estrous and kidding interval decreased significantly, while conception rate increased due to adding RPC. Milk choline concentrations and total choline secretion though milk were progressively increased significantly with increasing the level of RPC supplementation. Live body weight and daily body gain of their suckling male and female kids at weaning increased significantly with increasing RPC levels in the diets of their mothers. © 2017 Japanese Society of Animal Science.

  15. Intergenic sequence between Arabidopsis caseinolytic protease B-cytoplasmic/heat shock protein100 and choline kinase genes functions as a heat-inducible bidirectional promoter.

    Science.gov (United States)

    Mishra, Ratnesh Chandra; Grover, Anil

    2014-11-01

    In Arabidopsis (Arabidopsis thaliana), the At1g74310 locus encodes for caseinolytic protease B-cytoplasmic (ClpB-C)/heat shock protein100 protein (AtClpB-C), which is critical for the acquisition of thermotolerance, and At1g74320 encodes for choline kinase (AtCK2) that catalyzes the first reaction in the Kennedy pathway for phosphatidylcholine biosynthesis. Previous work has established that the knockout mutants of these genes display heat-sensitive phenotypes. While analyzing the AtClpB-C promoter and upstream genomic regions in this study, we noted that AtClpB-C and AtCK2 genes are head-to-head oriented on chromosome 1 of the Arabidopsis genome. Expression analysis showed that transcripts of these genes are rapidly induced in response to heat stress treatment. In stably transformed Arabidopsis plants harboring this intergenic sequence between head-to-head oriented green fluorescent protein and β-glucuronidase reporter genes, both transcripts and proteins of the two reporters were up-regulated upon heat stress. Four heat shock elements were noted in the intergenic region by in silico analysis. In the homozygous transfer DNA insertion mutant Salk_014505, 4,393-bp transfer DNA is inserted at position -517 upstream of ATG of the AtClpB-C gene. As a result, AtCk2 loses proximity to three of the four heat shock elements in the mutant line. Heat-inducible expression of the AtCK2 transcript was completely lost, whereas the expression of AtClpB-C was not affected in the mutant plants. Our results suggest that the 1,329-bp intergenic fragment functions as a heat-inducible bidirectional promoter and the region governing the heat inducibility is possibly shared between the two genes. We propose a model in which AtClpB-C shares its regulatory region with heat-induced choline kinase, which has a possible role in heat signaling. © 2014 American Society of Plant Biologists. All Rights Reserved.

  16. A novel digestion method based on a choline chloride–oxalic acid deep eutectic solvent for determining Cu, Fe, and Zn in fish samples

    Energy Technology Data Exchange (ETDEWEB)

    Habibi, Emadaldin [Department of Marine Chemistry, Faculty of Marine Science, Khorramshahr University of Marine Science and Technology, P.O. BOX 669, Khorramshahr (Iran, Islamic Republic of); Ghanemi, Kamal, E-mail: Kamal.ghanemi@kmsu.ac.ir [Department of Marine Chemistry, Faculty of Marine Science, Khorramshahr University of Marine Science and Technology, P.O. BOX 669, Khorramshahr (Iran, Islamic Republic of); Marine Science Research Institute, Khorramshahr University of Marine Science and Technology, Khorramshahr (Iran, Islamic Republic of); Fallah-Mehrjardi, Mehdi [Department of Marine Chemistry, Faculty of Marine Science, Khorramshahr University of Marine Science and Technology, P.O. BOX 669, Khorramshahr (Iran, Islamic Republic of); Marine Science Research Institute, Khorramshahr University of Marine Science and Technology, Khorramshahr (Iran, Islamic Republic of); Dadolahi-Sohrab, Ali [Department of Marine Environment, Faculty of marine natural resources, Khorramshahr University of Marine Science and Technology, Khorramshahr (Iran, Islamic Republic of)

    2013-01-31

    Highlights: ► A novel digestion method: lack of concentrated acids or oxidizing reagents. ► First report of using choline chloride–oxalic acid (ChCl–Ox) for digestion. ► Complete dissolution of biological samples in ChCl–Ox for solubilization metals. ► Extraction recoveries greater than 95%: validated by the fish protein CRM. ► Successfully applied in different fish tissues (Muscle, Liver, and Gills). -- Abstract: A novel and efficient digestion method based on choline chloride–oxalic acid (ChCl–Ox) deep eutectic solvent (DES) was developed for flame atomic absorption spectrometry (FAAS) determination of Cu, Zn, and Fe in biological fish samples. Key parameters that influence analyte recovery were investigated and optimized, using the fish protein certified reference material (CRM, DORM-3) throughout the procedure. In this method, 100 mg of the sample was dissolved in ChCl–Ox (1:2, molar ratio) at 100 °C for 45 min. Then, 5.0 mL HNO{sub 3} (1.0 M) was added. After centrifugation, the supernatant solution was filtered, diluted to a known volume, and analyzed by FAAS. Under optimized conditions, an excellent agreement between the obtained results and the certified values was observed, using Student's t-test (P = 0.05); the extraction recovery of the all elements was greater than 95.3%. The proposed method was successfully applied to the determination of analytes in different tissues (muscle, liver, and gills) having a broad concentration range in a marine fish sample. The reproducibility of the method was validated by analyzing all samples by our method in a different laboratory, using inductively coupled plasma optical emission spectrometry (ICP-OES). For comparison, a conventional acid digestion (CAD) method was also used for the determination of analytes in all studied samples. The simplicity of the proposed experimental procedure, high extraction efficiency, short analysis time, lack of concentrated acids and oxidizing agents, and the

  17. A novel digestion method based on a choline chloride–oxalic acid deep eutectic solvent for determining Cu, Fe, and Zn in fish samples

    International Nuclear Information System (INIS)

    Habibi, Emadaldin; Ghanemi, Kamal; Fallah-Mehrjardi, Mehdi; Dadolahi-Sohrab, Ali

    2013-01-01

    Highlights: ► A novel digestion method: lack of concentrated acids or oxidizing reagents. ► First report of using choline chloride–oxalic acid (ChCl–Ox) for digestion. ► Complete dissolution of biological samples in ChCl–Ox for solubilization metals. ► Extraction recoveries greater than 95%: validated by the fish protein CRM. ► Successfully applied in different fish tissues (Muscle, Liver, and Gills). -- Abstract: A novel and efficient digestion method based on choline chloride–oxalic acid (ChCl–Ox) deep eutectic solvent (DES) was developed for flame atomic absorption spectrometry (FAAS) determination of Cu, Zn, and Fe in biological fish samples. Key parameters that influence analyte recovery were investigated and optimized, using the fish protein certified reference material (CRM, DORM-3) throughout the procedure. In this method, 100 mg of the sample was dissolved in ChCl–Ox (1:2, molar ratio) at 100 °C for 45 min. Then, 5.0 mL HNO 3 (1.0 M) was added. After centrifugation, the supernatant solution was filtered, diluted to a known volume, and analyzed by FAAS. Under optimized conditions, an excellent agreement between the obtained results and the certified values was observed, using Student's t-test (P = 0.05); the extraction recovery of the all elements was greater than 95.3%. The proposed method was successfully applied to the determination of analytes in different tissues (muscle, liver, and gills) having a broad concentration range in a marine fish sample. The reproducibility of the method was validated by analyzing all samples by our method in a different laboratory, using inductively coupled plasma optical emission spectrometry (ICP-OES). For comparison, a conventional acid digestion (CAD) method was also used for the determination of analytes in all studied samples. The simplicity of the proposed experimental procedure, high extraction efficiency, short analysis time, lack of concentrated acids and oxidizing agents, and the use of

  18. Dietary choline and phospholipid supplementation enhanced docosahexaenoic acid enrichment in egg yolk of laying hens fed a 2% Schizochytrium powder-added diet.

    Science.gov (United States)

    Wang, H; Zhang, H J; Wang, X C; Wu, S G; Wang, J; Xu, L; Qi, G H

    2017-08-01

    The aim of this study was to evaluate the effect of dietary phospholipid supplementation on laying hen performance, egg quality, and the fatty acid profile of egg yolks from hens fed a 2% Schizochytrium powder diet. Three-hundred-sixty 28-wk-old Hy-line W-36 laying hens were randomly allocated to one of the 5 dietary treatments, each treatment with 6 replicates of 12 birds each. All diets included 2% Schizochytrium powder (docosahexaenoic acid [DHA], 137.09 mg/g). The control group was not supplemented with any additional phospholipids, whereas the other 4 experimental diets were supplemented with 1,000 mg/kg choline (CHO), 1,000 mg/kg monoethanolamine (MEA), 1,000 mg/kg lysophosphatidylcholine (LPC), or 500 mg/kg LPC + 500 mg/kg MEA (LPC + MEA). The experimental diets were isocaloric (metabolizable energy, 11.15 MJ/kg) and isonitrogenous (crude protein, 16.60%). The feeding trial lasted 28 days. Laying hen performance and egg quality were not affected (P > 0.05) by the diets used. The monounsaturated fatty acid (MUFA) level was reduced in the LPC group at d 28 (P egg yolks in the LPC group had a trend to increase in comparison to the control (P = 0.07). The CHO and LPC groups had higher omega-3 (n-3) PUFA and DHA levels and lower n-6/n-3 ratios than the other groups at d 28 (P egg yolk reached a plateau after the laying hens consumed the experimental diets for 14 days, and higher yolk DHA contents were observed in the CHO and LPC groups as compared with the other groups at d 14. It was concluded that dietary choline supplementation for more than 14 d enhanced egg yolk enrichment with n-3 PUFA and DHA when laying hen diets were supplemented with 2% Schizochytrium powder. All the diets had no adverse effect on hen performance, egg quality, or egg components under the experimental condition. © 2017 Poultry Science Association Inc.

  19. Role of 11C-choline positron emission tomography/computed tomography in evaluating patients affected by prostate cancer with suspected relapse due to prostate-specific antigen elevation

    International Nuclear Information System (INIS)

    Bertagna, F.; Bosio, G.; Abuhilal, M.

    2011-01-01

    The aim of this study was to evaluate the accuracy of 11 C-choline positron emission tomography/computed tomography (PET/CT) in restaging patients affected by prostate cancer and suspected relapse due to prostate-specific antigen (PSA) increase. We also aimed to determine a PSA cutoff that is most suited to the study in terms of best compromise between sensitivity and specificity. Secondary endpoints were a comparison between 11 C-choline PET/CT and histological results, clinical findings, and radiological imaging (CT and magnetic resonance imaging). We retrospectively evaluated 210 patients (median±standard deviation (SD) age 70±7 years) affected by prostate cancer who underwent 11 C-choline PET/CT. 11 C-choline PET/CT imaging was positive in 116 (55.2%) patients and negative in 94 (44.8%). Receiver operating characteristic (ROC) analysis showed that the highest accuracy (sensitivity 76.8%, specificity 92.5%) for the whole population was achieved when the PSA level of 1.26 ng/ml level was used as the cutoff value for interpreting the results (P=0.0001 and the area under the ROC curve area under the curve (AUC)=0.897). For patients treated with surgery or surgery plus radiotherapy the cutoff was 0.81 ng/ml (sensitivity 73.2%, specificity 86.1%). For patients treated with radiotherapy alone, the cutoff was 2.0 ng/ml (sensitivity 81.8%, specificity 92.9%). Our results indicate that 11 C-choline PET/CT is a useful diagnostic tool in patients affected by prostate cancer and a relapsed PSA level. The highest accuracy for all patients is obtained with a PSA cutoff level of 1.26 ng/ml, above which the imaging study is performed (0.81 ng/ml for patients treated with surgery or surgery plus radiotherapy and 2.0 ng/ml for patients treated with radiotherapy alone). (author)

  20. Desempenho produtivo de tilápia do Nilo alimentada com níveis de colina na dieta = Growth performance of Nile tilapia fed graded choline levels in the diet

    Directory of Open Access Journals (Sweden)

    Ademir Calvo Fernandes Junior

    2010-04-01

    Full Text Available Este estudo foi realizado com o objetivo de avaliar o desempenho produtivo da tilápia do Nilo (Oreochromis niloticus alimentada com níveis de colina na dieta pelo período de 109 dias. Foram utilizados 192 alevinos com 4,0 ± 0,15 g de peso médio, distribuídos em 32 tanques-rede de 200 L, na densidade de seis peixes por tanque-rede, dispostos em aquários de 1.000 L. O delineamento experimental foi inteiramente casualizado com oito tratamentos e quatro repetições. As rações foram suplementadas com 0, 100, 200, 400, 600, 800, 1.000 e 1.200 mg de colina kg-1 de ração. Não foram observadas diferenças para ganho de peso, taxa de sobrevivência, conversão alimentar aparente, porcentagem de extrato etéreo do filé e do fígado, índice hepatossomático e concentração de lipídeos no plasma. Concluiuseque os diferentes níveis de colina não melhoraram o desempenho produtivo dos peixes nestas condições, pois a dieta basal supostamente supriu a exigência do peixe para colina.A 109-day feeding trial was undertaken aiming to evaluate the growth performance of Nile tilapia fed graded choline levels. One hundred and ninety-two (initial weight 4.0 ± 0.15 g fingerlings were distributed into 32 net cages (200 L each, four cages per treatmentand six fish per cage, placed in eight 1000L aquaria in a closed recirculation system. The treatments were assigned to the tanks comprising eight treatments and four replications arranged in a completely randomized experimental design. Diets were supplemented with choline chloride to provide 100, 200, 400, 600, 800, 1000, 1200 mg of choline per kg of feed and an unsupplemented diet. No significant differences were observed in growth performance, survival, apparent feed conversion, liver and fillet ether extract, hepatosomatic index and plasma lipid concentration, among treatments. Choline levels did not improve growth performance, possibly because the amount of choline in the diet had already met fish

  1. Independently recruited oxidases from the glucose-methanol-choline oxidoreductase family enabled chemical defences in leaf beetle larvae (subtribe Chrysomelina) to evolve

    Science.gov (United States)

    Rahfeld, Peter; Kirsch, Roy; Kugel, Susann; Wielsch, Natalie; Stock, Magdalena; Groth, Marco; Boland, Wilhelm; Burse, Antje

    2014-01-01

    Larvae of the leaf beetle subtribe Chrysomelina sensu stricto repel their enemies by displaying glandular secretions that contain defensive compounds. These repellents can be produced either de novo (iridoids) or by using plant-derived precursors (e.g. salicylaldehyde). The autonomous production of iridoids, as in Phaedon cochleariae, is the ancestral chrysomeline chemical defence and predates the evolution of salicylaldehyde-based defence. Both biosynthesis strategies include an oxidative step of an alcohol intermediate. In salicylaldehyde-producing species, this step is catalysed by salicyl alcohol oxidases (SAOs) of the glucose-methanol-choline (GMC) oxidoreductase superfamily, but the enzyme oxidizing the iridoid precursor is unknown. Here, we show by in vitro as well as in vivo experiments that P. cochleariae also uses an oxidase from the GMC superfamily for defensive purposes. However, our phylogenetic analysis of chrysomeline GMC oxidoreductases revealed that the oxidase of the iridoid pathway originated from a GMC clade different from that of the SAOs. Thus, the evolution of a host-independent chemical defence followed by a shift to a host-dependent chemical defence in chrysomeline beetles coincided with the utilization of genes from different GMC subfamilies. These findings illustrate the importance of the GMC multi-gene family for adaptive processes in plant–insect interactions. PMID:24943369

  2. Electrodeposition of a Au-Dy2O3 Composite Solid Oxide Fuel Cell Catalyst from Eutectic Urea/Choline Chloride Ionic Liquid

    Directory of Open Access Journals (Sweden)

    Claudio Mele

    2012-12-01

    Full Text Available  In this research we have fabricated and tested Au/Dy2O3 composites for applications as Solid Oxide Fuel Cell (SOFC electrocatalysts. The material was obtained by a process involving electrodeposition of a Au-Dy alloy from a urea/choline chloride ionic liquid electrolyte, followed by selective oxidation of Dy to Dy2O3 in air at high temperature. The electrochemical kinetics of the electrodeposition bath were studied by cyclic voltammetry, whence optimal electrodeposition conditions were identified. The heat-treated material was characterised from the morphological (scanning electron microscopy, compositional (X-ray fluorescence spectroscopy and structural (X-ray diffractometry points of view. The electrocatalytic activity towards H2 oxidation and O2 reduction was tested at 650 °C by electrochemical impedance spectrometry. Our composite electrodes exhibit an anodic activity that compares favourably with the only literature result available at the time of this writing for Dy2O3 and an even better cathodic performance.

  3. Selective cortical decrease of high-affinity choline uptake carrier in Alzheimer's disease: an autoradiographic study using 3H-hemicholinium-3

    International Nuclear Information System (INIS)

    Rodriguez-Puertas, R.; Pazos, A.; Zarranz, J.J.; Pascual, J.

    1994-01-01

    H-hemicholinium-3 (H-HC-3) binding, a marker of the presynaptic high-affinity choline uptake carrier (HACU), was measured by autoradiography in several brain regions of 17 Alzheimer's disease (AD) patients and of 11 matched controls. A significant decrease in the density of H-HC-3 binding sites was found in entorhinal cortex, hippocampus and layers I-III of the frontal cortex. By contrast, in the caudate-putamen the number of H-HC-3 binding sites in AD cases was comparable to that of control striata. These data concur with previous results using classical presynaptic markers and reflect the loss in the activity of HACU, and, hence, in the synthesis of acetylcholine, that selectively occurs in cortical areas of AD brains due to the degeneration of presynaptic cholinergic terminals arising from the basal forebrain. However, the relatively low mean reduction in HACU in cortical areas (-40 %), together with the apparent indemnity of this marker in certain severely demented AD cases, suggest that AD dementia cannot be explained simply by the loss of presynaptic terminals originating in the basal forebrain. These data seem to be a good explanation for the poor response to cholinergic replacement in AD. (author)

  4. A Choline Oxidase Amperometric Bioassay for the Detection of Mustard Agents Based on Screen-Printed Electrodes Modified with Prussian Blue Nanoparticles

    Directory of Open Access Journals (Sweden)

    Fabiana Arduini

    2015-02-01

    Full Text Available In this work a novel bioassay for mustard agent detection was proposed. The bioassay is based on the capability of these compounds to inhibit the enzyme choline oxidase. The enzymatic activity, which is correlated to the mustard agents, was electrochemically monitored measuring the enzymatic product, hydrogen peroxide, by means of a screen-printed electrode modified with Prussian Blue nanoparticles. Prussian Blue nanoparticles are able to electrocatalyse the hydrogen peroxide concentration reduction at low applied potential (−50 mV vs. Ag/AgCl, thus allowing the detection of the mustard agents with no electrochemical interferences. The suitability of this novel bioassay was tested with the nitrogen mustard simulant bis(2-chloroethylamine and the sulfur mustard simulants 2-chloroethyl ethyl sulfide and 2-chloroethyl phenyl sulfide. The bioassay proposed in this work allowed the detection of mustard agent simulants with good sensitivity and fast response, which are excellent premises for the development of a miniaturised sensor well suited for an alarm system in case of terrorist attacks.

  5. Selective cortical decrease of high-affinity choline uptake carrier in Alzheimer`s disease: an autoradiographic study using {sup 3}H-hemicholinium-3

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Puertas, R; Pazos, A [Dept. of Physiology and Pharmacology, Unit of Pharmacology, Univ. of Cantabria, Santander (Spain); Zarranz, J J [Dept. of Neuroscience, Univ. of the Basque Country, Leioa (Spain); Pascual, J [Dept. of Medicine, Service of Neurology, Univ. Hospital ` Marques de Valdecilla` , Univ. of Cantabria, Santander (Spain)

    1994-12-31

    H-hemicholinium-3 (H-HC-3) binding, a marker of the presynaptic high-affinity choline uptake carrier (HACU), was measured by autoradiography in several brain regions of 17 Alzheimer`s disease (AD) patients and of 11 matched controls. A significant decrease in the density of H-HC-3 binding sites was found in entorhinal cortex, hippocampus and layers I-III of the frontal cortex. By contrast, in the caudate-putamen the number of H-HC-3 binding sites in AD cases was comparable to that of control striata. These data concur with previous results using classical presynaptic markers and reflect the loss in the activity of HACU, and, hence, in the synthesis of acetylcholine, that selectively occurs in cortical areas of AD brains due to the degeneration of presynaptic cholinergic terminals arising from the basal forebrain. However, the relatively low mean reduction in HACU in cortical areas (-40 %), together with the apparent indemnity of this marker in certain severely demented AD cases, suggest that AD dementia cannot be explained simply by the loss of presynaptic terminals originating in the basal forebrain. These data seem to be a good explanation for the poor response to cholinergic replacement in AD. (author).

  6. Voltage sensitivity of M2 muscarinic receptors underlies the delayed rectifier-like activation of ACh-gated K(+) current by choline in feline atrial myocytes.

    Science.gov (United States)

    Navarro-Polanco, Ricardo A; Aréchiga-Figueroa, Iván A; Salazar-Fajardo, Pedro D; Benavides-Haro, Dora E; Rodríguez-Elías, Julio C; Sachse, Frank B; Tristani-Firouzi, Martin; Sánchez-Chapula, José A; Moreno-Galindo, Eloy G

    2013-09-01

    Choline (Ch) is a precursor and metabolite of the neurotransmitter acetylcholine (ACh). In canine and guinea pig atrial myocytes, Ch was shown to activate an outward K(+) current in a delayed rectifier fashion. This current has been suggested to modulate cardiac electrical activity and to play a role in atrial fibrillation pathophysiology. However, the exact nature and identity of this current has not been convincingly established. We recently described the unique ligand- and voltage-dependent properties of muscarinic activation of ACh-activated K(+) current (IKACh) and showed that, in contrast to ACh, pilocarpine induces a current with delayed rectifier-like properties with membrane depolarization. Here, we tested the hypothesis that Ch activates IKACh in feline atrial myocytes in a voltage-dependent manner similar to pilocarpine. Single-channel recordings, biophysical profiles, specific pharmacological inhibition and computational data indicate that the current activated by Ch is IKACh. Moreover, we show that membrane depolarization increases the potency and efficacy of IKACh activation by Ch and thus gives the appearance of a delayed rectifier activating K(+) current at depolarized potentials. Our findings support the emerging concept that IKACh modulation is both voltage- and ligand-specific and reinforce the importance of these properties in understanding cardiac physiology.

  7. Over-expressing the soluble gp130-Fc does not ameliorate methionine and choline deficient diet-induced non alcoholic steatohepatitis in mice.

    Directory of Open Access Journals (Sweden)

    Helene L Kammoun

    Full Text Available Non-alcoholic steatohepatitis (NASH is a liver disease with the potential to lead to cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6 has been implicated in the pathogenesis of NASH, with the so-called IL-6 'trans-signaling' cascade being responsible for the pro-inflammatory actions of this cytokine. We aimed to block IL-6 'trans-signaling', using a transgenic mouse that overexpresses human soluble glycoprotein130 (sgp130Fc Tg mice fed a commonly used dietary model of inducing NASH (methionine and choline deficient-diet; MCD diet and hypothesized that markers of NASH would be ameliorated in such mice. Sgp130Fc Tg and littermate control mice were fed a MCD or control diet for 4 weeks. The MCD diet induced many hallmarks of NASH including hepatomegaly, steatosis, and liver inflammation. However, in contrast with other mouse models and, indeed, human NASH, the MCD diet model did not increase the mRNA or protein expression of IL-6. Not surprisingly, therefore, markers of MCD diet-induced NASH were unaffected by sgp130Fc transgenic expression. While the MCD diet model induces many pathophysiological markers of NASH, it does not induce increased IL-6 expression in the liver, a key hallmark of human NASH. We, therefore, caution the use of the MCD diet as a viable mouse model of NASH.

  8. In vivo relaxation of N-acetyl-aspartate, creatine plus phosphocreatine, and choline containing compounds during the course of brain infarction: a proton MRS study

    DEFF Research Database (Denmark)

    Gideon, P; Henriksen, O

    1992-01-01

    Localized water suppressed proton spectroscopy has opened up a new field of pathophysiological studies of severe brain ischemia. The signals obtained with the pulse sequences used so far are both T1 and T2 weighted. In order to evaluate the extent to which changes in metabolite signals during...... the course of infarction can be explained by changes in T1 and T2 relaxation times, eight patients with acute stroke were studied. STEAM sequences with varying echo delay times and repetition times were used to measure T1 and T2 of N-acetyl-aspartate (NAA), creatine plus phosphocreatine (Cr+PCr) and choline...... containing compounds (CHO) in a 27-ml voxel located in the affected area of the brain. Ten healthy volunteers served as controls. We found no difference in T1 or T2 of the metabolites between the patients and the normal controls. The T2 of CHO was longer than that of NAA and Cr+PCr. Our results indicate...

  9. Comparison between the efficacies of curcumin and puerarin in C57BL/6 mice with steatohepatitis induced by a methionine- and choline-deficient diet.

    Science.gov (United States)

    Wang, Yunliang; Li, Jian; Zhuge, Li; Su, Dongmei; Yang, Meijuan; Tao, Shiying; Li, Junxiang

    2014-03-01

    Non-alcoholic fatty liver disease (NAFLD) is a prevalent disease, which features an abnormal accumulation of lipids inside hepatocytes. Steatohepatitis plays a critical role in the process resulting in liver fibrosis and cirrhosis. Curcumin and puerarin are herbal products widely used in Asia, which are believed to have therapeutic benefits for alleviating the symptoms of steatohepatitis. In this study, mice models of steatohepatitis induced by a methionine- and choline-deficient diet (MCD) were established to compare the pharmacological actions of curcumin and puerarin. The results showed that curcumin and puerarin exerted inhibitory effects against MCD-induced steatohepatitis in mice. Briefly, curcumin and puerarin significantly downregulated the levels of tumor necrosis factor-α in the blood serum of mice (PMCD group). In addition, the levels of triglycerides, total cholesterol and low density lipoproteins in the serum were significantly reduced by puerarin treatment (PMCD group). The concentration of interleukin-6 was downregulated by curcumin only (PMCD group). Curcumin and puerarin significantly increased the levels of peroxisome proliferator-activated receptor-γ (PPARγ; PMCD group). Moreover, increased nuclear factor-κB (NF-κB) was markedly attenuated by curcumin (PMCD group). In conclusion, curcumin and puerarin appear to exert different actions against steatohepatitis. It is possible that puerarin regulated lipid metabolism in the 'first hit' stage through the PPARγ pathway, while curcumin inhibited the inflammatory response in the 'second hit' stage through the NF-κB pathway.

  10. Effects of rumen-protected methionine and choline supplementation on steroidogenic potential of the first postpartum dominant follicle and expression of immune mediators in Holstein cows.

    Science.gov (United States)

    Acosta, D A V; Rivelli, M I; Skenandore, C; Zhou, Z; Keisler, D H; Luchini, D; Corrêa, M N; Cardoso, F C

    2017-07-01

    Multiparous Holstein cows were assigned in a randomized complete block design into four treatments from 21 d before calving to 30 d in milk (DIM). Treatments were: MET [n = 19, fed the basal diet + rumen-protected methionine at a rate of 0.08% (w/w) of the dry matter, Smartamine ® M], CHO (n = 17, fed the basal diet + choline 60 g/d, Reashure ® ), MIX (n = 21, fed the basal diet + Smartamine ® M at a rate of 0.08% (w/w) of the dry matter and 60 g/d Reashure ® ), and CON (n = 20, no supplementation, fed the close-up and fresh cow diets). Follicular development was monitored via ultrasound every 2 d starting at 7 DIM until ovulation (n = 37) or aspiration (n = 40) of the first postpartum dominant follicle (DF). Follicular fluid from 40 cows was aspirated and cells were retrieved immediately by centrifugation. Gene expression of TLR4, TNF, IL1-β, IL8, IL6, LHCGR, STAR, 3β-HSD, P450scc, CYP19A1, IRS1, IGF, MAT1A, and SAHH, was measured in the follicular cells of the first DF. Cows in CON had higher TNF, TLR4, and IL1-β mRNA expression (11.70 ± 4.6, 21.29 ± 10.4, 6.28 ± 1.4, respectively) than CHO (2.77 ± 0.9, 2.16 ± 0.9, 2.29 ± 0.7, respectively), and MIX (2.23 ± 0.7, 1.46 ± 0.6, 2.92 ± 0.8, respectively). Cows in CON had higher IL1-β expression (6.27 ± 1.4) than cows in MET (3.28 ± 0.6). Expression of IL8 mRNA was lower for cows in CHO (0.98 ± 0.3) than cows in CON (4.90 ± 0.7), MET (6.10 ± 1.7), or MIX (5.05 ± 1.8). Treatments did not affect mRNA expression of LHCGR, STAR, P450scc, CYP19A, SAHH, MAT1A, or IL6 however, 3β-HSD expression was higher for cows in MET (1.46 ± 0.3) and MIX (1.25 ± 0.3) than CON (0.17 ± 0.04) and CHO (0.26 ± 0.1). Supplementation of methionine, choline, and both methionine and choline during the transition period did not affect days to first ovulation or number of cows that ovulated the first follicular wave. Plasma and follicular fluid estradiol and

  11. Colina e betaína em rações purificadas na nutrição da tilápia do Nilo (Oreochromis niloticus Choline and betaine in purified diets for Nile tilapia (Oreochromis niloticus

    Directory of Open Access Journals (Sweden)

    Ivan Vieira

    2001-12-01

    Full Text Available Problemas metabólicos observados em produções intensivas de tilápias do Nilo (Oreochromis niloticus têm sido relacionados à deficiência de colina nas rações. Com o objetivo de avaliar o efeito da suplementação dietética da colina na nutrição da espécie, rações purificadas contendo 0; 375; 750; 1.125; 1.500 ou 1.875 mg de cloreto de colina por kg, foram administradas ad libitum por 42 dias a tilápias do Nilo (5,09 ± 0,14 g, estocados em gaiolas de PVC atóxico (volume = 60 L, alojadas em caixas de polipropileno de 1000 L, em ambiente com condições controladas de temperatura e luminosidade, num delineamento experimental em blocos incompletos casualizados, com três parcelas por bloco (n=5. O ganho de peso (GDP e o índice de conversão alimentar (ICA de todos os tratamentos foram superiores ao controle. Não foram observadas diferenças para a quantidade de lipídios no fígado e tecido corporal, e sobrevivência (S%. Num segundo experimento, os peixes foram alimentados com rações suplementadas com 1.250 ou 2.500 mg de cloreto de colina por kg; ou 1.000; 2.000 ou 3.000 mg de betaína por kg. Não foram observadas diferenças significativas para S% e acúmulo de lipídeos hepáticos ou corporais; o ICA e GDP dos tratamentos suplementados com colina foram superiores aos dos tratamentos suplementados com betaína, mas não diferiram entre si. Níveis de suplementação superiores a 375 mg de cloreto de colina por kg de alimento melhoram o ICA e o GDP da tilápia do Nilo, mas a betaína não substitui efetivamente a colina em rações para a espécie.Metabolic problems detected in intensively raised Nile tilapia (Oreochromis niloticus are credited to possible sub-supplementation of coline in commercial feeds. To investigate the utilization of choline and betaine as feed supplement for the Nile tilapia, groups of 10 fingerlings (5.09 ± 0.14 g stocked in 30 PVC cages (60 L, kept under controlled environmental conditions inside

  12. Targeted metabolomics reveals reduced levels of polyunsaturated choline plasmalogens and a smaller dimethylarginine/arginine ratio in the follicular fluid of patients with a diminished ovarian reserve.

    Science.gov (United States)

    de la Barca, J M Chao; Boueilh, T; Simard, G; Boucret, L; Ferré-L'Hotellier, V; Tessier, L; Gadras, C; Bouet, P E; Descamps, P; Procaccio, V; Reynier, P; May-Panloup, P

    2017-11-01

    Does the metabolomic profile of the follicular fluid (FF) of patients with a diminished ovarian reserve (DOR) differ from that of patients with a normal ovarian reserve (NOR)? The metabolomic signature of the FF reveals a significant decrease in polyunsaturated choline plasmalogens and methyl arginine transferase activity in DOR patients compared to NOR patients. The composition of the FF reflects the exchanges between the oocyte and its microenvironment during its acquisition of gametic competence. Studies of the FF have allowed identification of biomarkers and metabolic pathways involved in various pathologies affecting oocyte quality, but no large metabolomic analysis in the context of ovarian ageing and DOR has been undertaken so far. This was an observational study of the FF retrieved from 57 women undergoing in vitro fertilization at the University Hospital of Angers, France, from November 2015 to September 2016. The women were classified in two groups: one including 28 DOR patients, and the other including 29 NOR patients, serving as controls. Patients were enrolled in the morning of oocyte retrieval after ovarian stimulation. Once the oocytes were isolated for fertilization and culture, the FF was pooled and centrifuged for analysis. A targeted quantitative metabolomic analysis was performed using high-performance liquid chromatography coupled with tandem mass spectrometry, and the Biocrates Absolute IDQ p180 kit. The FF levels of 188 metabolites and several sums and ratios of metabolic significance were assessed by multivariate and univariate analyses. A total of 136 metabolites were accurately quantified and used for calculating 23 sums and ratios. Samples were randomly divided into training and validation sets. The training set, allowed the construction of multivariate statistical models with a projection-supervised method, i.e. orthogonal partial least squares discriminant analysis (OPLS-DA), applied to the full set of metabolites, or the penalized

  13. Probing topology and dynamics of the second transmembrane domain (M2δ) of the acetyl choline receptor using magnetically aligned lipid bilayers (bicelles) and EPR spectroscopy.

    Science.gov (United States)

    Sahu, Indra D; Mayo, Daniel J; Subbaraman, Nidhi; Inbaraj, Johnson J; McCarrick, Robert M; Lorigan, Gary A

    2017-08-01

    Characterizing membrane protein structure and dynamics in the lipid bilayer membrane is very important but experimentally challenging. EPR spectroscopy offers a unique set of techniques to investigate a membrane protein structure, dynamics, topology, and distance constraints in lipid bilayers. Previously our lab demonstrated the use of magnetically aligned phospholipid bilayers (bicelles) for probing topology and dynamics of the membrane peptide M2δ of the acetyl choline receptor (AchR) as a proof of concept. In this study, magnetically aligned phospholipid bilayers and rigid spin labels were further utilized to provide improved dynamic information and topology of M2δ peptide. Seven TOAC-labeled AchR M2δ peptides were synthesized to demonstrate the utility of a multi-labeling amino acid substitution alignment strategy. Our data revealed the helical tilts to be 11°, 17°, 9°, 17°, 16°, 11°, 9°±4° for residues I7TOAC, Q13TOAC, A14TOAC, V15TOAC, C16TOAC, L17TOAC, and L18TOAC, respectively. The average helical tilt of the M2δ peptide was determined to be ∼13°. This study also revealed that the TOAC labels were attached to the M2δ peptide with different dynamics suggesting that the sites towards the C-terminal end are more rigid when compared to the sites towards the N-terminus. The dynamics of the TOAC labeled sites were more resolved in the aligned samples when compared to the randomly disordered samples. This study highlights the use of magnetically aligned lipid bilayer EPR technique to determine a more accurate helical tilt and more resolved local dynamics of AchR M2δ peptide. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. N-acetylaspartate, choline and myoinositol concentration changes in MR spectroscopy (1H MRS) of hippocampal formation in patients with mild cognitive impairment (MCI) - preliminary study

    International Nuclear Information System (INIS)

    Pawlowska, A.; Cwikla, J.; Walecki, J.; Gabryelewicz, T.; Barcikowska, M.

    2004-01-01

    Cognitive and memory impairment are very common problems in elderly patients. Mild cognitive impairment (MCI) is known as a transitional clinical state between normal ('successful') aging and dementia. In some cases MCI may be a precursor to Alzheimer's disease (AD). Early neuronal loss and metabolic changes have been documented in previous studies in AD patients in some 'strategic ' regions of the brain, mainly in hippocampal formation. Our goal was to determine whether there are statistically significant changes in hippocampal N-acetylaspartate, choline and myoinositol levels obtained by single-voxel spectroscopy in MCI patients and normal aging and to evaluate its clinical diagnostic utility. 30 patients with MCI and 15 cognitively normal elderly subjects underwent proton MR spectroscopy at 1.5 T system. MR spectra were obtained from anterior and posterior part of hippocampal formation bilaterally, using the point-resolved spectroscopy sequence. Metabolite ratios of NAA/H 2 O, Cho/H 2 O and mI/H 2 O were calculated from the peak height measurements. Relative to the control group, patients with MCI demonstrated elevated mI/H 2 O and Cho/H 2 O ratios in both hippocampal formations. The most significant increase was observed in mI/H 2 O ratio in anterior part of left hippocampus and in Cho/H 2 O ratio in posterior part of right hippocampus, in MCI patients vs.cognitively normal elderly. There were no significant differences between mean NAA/H 2 O ratios measured in hippocampal formation in both groups. Proton MRS may be used as valuable additional tool in the evaluation of regional metabolic changes in patients with MCI. Increase of mI and Cho levels in hippocampal formation may be an early sign of cognitive impairment in elderly subjects that can be measured using MRS. (author)

  15. Comparison of [11C]choline Positron Emission Tomography With T2- and Diffusion-Weighted Magnetic Resonance Imaging for Delineating Malignant Intraprostatic Lesions

    International Nuclear Information System (INIS)

    Chang, Joe H.; Lim Joon, Daryl; Davis, Ian D.; Lee, Sze Ting; Hiew, Chee-Yan; Esler, Stephen; Gong, Sylvia J.; Wada, Morikatsu; Clouston, David; O'Sullivan, Richard; Goh, Yin P.; Bolton, Damien; Scott, Andrew M.; Khoo, Vincent

    2015-01-01

    Purpose: The purpose of this study was to compare the accuracy of [ 11 C]choline positron emission tomography (CHOL-PET) with that of the combination of T2-weighted and diffusion-weighted (T2W/DW) magnetic resonance imaging (MRI) for delineating malignant intraprostatic lesions (IPLs) for guiding focal therapies and to investigate factors predicting the accuracy of CHOL-PET. Methods and Materials: This study included 21 patients who underwent CHOL-PET and T2W/DW MRI prior to radical prostatectomy. Two observers manually delineated IPL contours for each scan, and automatic IPL contours were generated on CHOL-PET based on varying proportions of the maximum standardized uptake value (SUV). IPLs identified on prostatectomy specimens defined reference standard contours. The imaging-based contours were compared with the reference standard contours using Dice similarity coefficient (DSC), and sensitivity and specificity values. Factors that could potentially predict the DSC of the best contouring method were analyzed using linear models. Results: The best automatic contouring method, 60% of the maximum SUV (SUV 60 ) , had similar correlations (DSC: 0.59) with the manual PET contours (DSC: 0.52, P=.127) and significantly better correlations than the manual MRI contours (DSC: 0.37, P<.001). The sensitivity and specificity values were 72% and 71% for SUV 60 ; 53% and 86% for PET manual contouring; and 28% and 92% for MRI manual contouring. The tumor volume and transition zone pattern could independently predict the accuracy of CHOL-PET. Conclusions: CHOL-PET is superior to the combination of T2W/DW MRI for delineating IPLs. The accuracy of CHOL-PET is insufficient for gland-sparing focal therapies but may be accurate enough for focal boost therapies. The transition zone pattern is a new classification that may predict how well CHOL-PET delineates IPLs

  16. Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet

    International Nuclear Information System (INIS)

    Akita, Shingo; Kubota, Koji; Kobayashi, Akira; Misawa, Ryosuke; Shimizu, Akira; Nakata, Takenari; Yokoyama, Takahide; Takahashi, Masafumi; Miyagawa, Shinichi

    2012-01-01

    Highlights: ► BMC-derived PSCs play a role in a rat CDE diet-induced pancreatitis model. ► BMC-derived PSCs contribute mainly to the early stage of pancreatic fibrosis. ► BMC-derived activated PSCs can produce PDGF and TGF β1. -- Abstract: Bone marrow cell (BMC)-derived myofibroblast-like cells have been reported in various organs, including the pancreas. However, the contribution of these cells to pancreatic fibrosis has not been fully discussed. The present study examined the possible involvement of pancreatic stellate cells (PSCs) originating from BMCs in the development of pancreatic fibrosis in a clinically relevant rat model of acute pancreatitis induced by a choline-deficient/ethionine-supplemented (CDE) diet. BMCs from female transgenic mice ubiquitously expressing green fluorescent protein (GFP) were transplanted into lethally irradiated male rats. Once chimerism was established, acute pancreatitis was induced by a CDE diet. Chronological changes in the number of PSCs originating from the donor BMCs were examined using double immunofluorescence for GFP and markers for PSCs, such as desmin and alpha smooth muscle actin (αSMA), 1, 3 and 8 weeks after the initiation of CDE feeding. We also used immunohistochemical staining to evaluate whether the PSCs from the BMCs produce growth factors, such as platelet-derived growth factor (PDGF) and transforming growth factor (TGF) β1. The percentage of BMC-derived activated PSCs increased significantly, peaking after 1 week of CDE treatment (accounting for 23.3 ± 0.9% of the total population of activated PSCs) and then decreasing. These cells produced both PDGF and TGFβ1 during the early stage of pancreatic fibrosis. Our results suggest that PSCs originating from BMCs contribute mainly to the early stage of pancreatic injury, at least in part, by producing growth factors in a rat CDE diet-induced pancreatitis model.

  17. Structural analysis by reductive cleavage with LiAlH4 of an allyl ether choline-phospholipid, archaetidylcholine, from the hyperthermophilic methanoarchaeon Methanopyrus kandleri

    Directory of Open Access Journals (Sweden)

    Masateru Nishihara

    2002-01-01

    Full Text Available A choline-containing phospholipid (PL-4 in Methanopyrus kandleri cells was identified as archaetidylcholine, which has been described by Sprott et al. (1997. The PL-4 consisted of a variety of molecular species differing in hydrocarbon composition. Most of the PL-4 was acid-labile because of its allyl ether bond. The identity of PL-4 was confirmed by thin-layer chromatography (TLC followed by positive staining with Dragendorff-reagent and fast-atom bombardment–mass spectrometry. A new method of LiAlH4 hydrogenolysis was developed to cleave allyl ether bonds and recover the corresponding hydrocarbons. We confirmed the validity of the LiAlH4 method in a study of the model compound synthetic unsaturated archaetidic acid (2,3-di-O-geranylgeranyl-sn-glycerol-1-phosphate. Saturated ether bonds were not cleaved by the LiAlH4 method. The hydrocarbons formed following LiAlH4 hydrogenolysis of PL-4 were identified by gas–liquid chromatography and mass spectrometry. Four kinds of hydrocarbons with one to four double bonds were detected: 47% of the hydrocarbons had four double bonds; 11% had three double bonds; 14% had two double bonds; 7% had one double bond; and 6% were saturated species. The molecular species composition of PL-4 was also estimated based on acid lability: 77% of the molecular species had two acid-labile hydrocarbons; 11% had one acid-labile and one acid-stable hydrocarbon; and 11% had two acid-stable hydrocarbons. To our knowledge, this is the first report of a specific chemical degradation method for the structural analysis of allyl ether phospholipid in archaea.

  18. Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet

    Energy Technology Data Exchange (ETDEWEB)

    Akita, Shingo; Kubota, Koji [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Kobayashi, Akira, E-mail: kbys@shinshu-u.ac.jp [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Misawa, Ryosuke; Shimizu, Akira; Nakata, Takenari; Yokoyama, Takahide [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Takahashi, Masafumi [Center for Molecular Medicine Division of Bioimaging Sciences, Jichi Medical University, 3311-1 Yakushiji, Shimono, Tochigi 329-0498 (Japan); Miyagawa, Shinichi [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer BMC-derived PSCs play a role in a rat CDE diet-induced pancreatitis model. Black-Right-Pointing-Pointer BMC-derived PSCs contribute mainly to the early stage of pancreatic fibrosis. Black-Right-Pointing-Pointer BMC-derived activated PSCs can produce PDGF and TGF {beta}1. -- Abstract: Bone marrow cell (BMC)-derived myofibroblast-like cells have been reported in various organs, including the pancreas. However, the contribution of these cells to pancreatic fibrosis has not been fully discussed. The present study examined the possible involvement of pancreatic stellate cells (PSCs) originating from BMCs in the development of pancreatic fibrosis in a clinically relevant rat model of acute pancreatitis induced by a choline-deficient/ethionine-supplemented (CDE) diet. BMCs from female transgenic mice ubiquitously expressing green fluorescent protein (GFP) were transplanted into lethally irradiated male rats. Once chimerism was established, acute pancreatitis was induced by a CDE diet. Chronological changes in the number of PSCs originating from the donor BMCs were examined using double immunofluorescence for GFP and markers for PSCs, such as desmin and alpha smooth muscle actin ({alpha}SMA), 1, 3 and 8 weeks after the initiation of CDE feeding. We also used immunohistochemical staining to evaluate whether the PSCs from the BMCs produce growth factors, such as platelet-derived growth factor (PDGF) and transforming growth factor (TGF) {beta}1. The percentage of BMC-derived activated PSCs increased significantly, peaking after 1 week of CDE treatment (accounting for 23.3 {+-} 0.9% of the total population of activated PSCs) and then decreasing. These cells produced both PDGF and TGF{beta}1 during the early stage of pancreatic fibrosis. Our results suggest that PSCs originating from BMCs contribute mainly to the early stage of pancreatic injury, at least in part, by producing growth factors in a rat CDE diet-induced pancreatitis model.

  19. 1H-MRS evaluation of breast lesions by using total choline signal-to-noise ratio as an indicator of malignancy: a meta-analysis.

    Science.gov (United States)

    Wang, Xin; Wang, Xiang Jiang; Song, Hui Sheng; Chen, Long Hua

    2015-05-01

    The aim of this study was to evaluate the diagnostic performance of the use of total choline signal-to-noise ratio (tCho SNR) criteria in MRS studies for benign/malignant discrimination of focal breast lesions. We conducted (1) a meta-analysis based on 10 studies including 480 malignant breast lesions and 312 benign breast lesions and (2) a subgroup meta-analysis of tCho SNR ≥ 2 as cutoff for malignancy based on 7 studies including 371 malignant breast lesions and 239 benign breast lesions. (1) The pooled sensitivity and specificity of proton MRS with tCho SNR were 0.74 (95 % CI 0.69-0.77) and 0.76 (95 % CI 0.71-0.81), respectively. The PLR and NLR were 3.67 (95 % CI 2.30-5.83) and 0.25 (95 % CI 0.14-0.42), respectively. From the fitted SROC, the AUC and Q* index were 0.89 and 0.82. Publication bias was present (t = 2.46, P = 0.039). (2) Meta-regression analysis suggested that neither threshold effect nor evaluated covariates including strength of field, pulse sequence, TR and TE were sources of heterogeneity (all P value >0.05). (3) Subgroup meta-analysis: The pooled sensitivity and specificity were 0.79 and 0.72, respectively. The PLR and NLR were 3.49 and 0.20, respectively. The AUC and Q* index were 0.92 and 0.85. The use of tCho SNR criteria in MRS studies was helpful for differentiation between malignant and benign breast lesions. However, pooled diagnostic measures might be overestimated due to publication bias. A tCho SNR ≥ 2 as cutoff for malignancy resulted in higher diagnostic accuracy.

  20. Pattern of occult nodal relapse diagnosed with 18F-fluoro-choline PET/CT in prostate cancer patients with biochemical failure after prostate-only radiotherapy

    International Nuclear Information System (INIS)

    Lépinoy, Alexis; Cochet, Alexandre; Cueff, Adèle; Cormier, Luc; Martin, Etienne; Maingon, Philippe; Bosset, Jean François; Brunotte, François; Créhange, Gilles

    2014-01-01

    Introduction: The purpose of this study was to describe the pattern of nodal relapse with 18 F-fluoro-choline (FCH) Positron Emission Tomography/Computerized Tomography (PET/CT) in prostate cancer patients after radiotherapy. Materials and methods: Eighty-three patients had a FCH PET/CT at time of biochemical failure. Of 65 patients with positive findings, 33 had positive nodes. This analysis included 31 patients who had undergone prior prostate-only radiotherapy with or without a prior radical prostatectomy. Each FCH positive node was assigned to a lymph node station with respect to the CTV defined by the RTOG guidelines (CTV RTOG ). 3D mapping was performed after each node was manually placed in a reference planning CT scan after automatic co-registration of the two scans based on bone anatomy. Eighteen patients (58%) underwent focal salvage FCH PET-guided stereotactic radiotherapy with no hormones. Results: Fourteen patients (45.2%) had a relapse outside the CTV RTOG . Of the 17 patients with a positive node inside the CTV RTOG , 15 had a single node (88.2%) while seven patients out of the 13 evaluable patients (53.9%) who had a relapse outside the CTV RTOG had ⩾2 positive nodes on FCH PET/CT (OR = 8.75, [95% CI: 1.38–54.80], p = 0.020). Relapses that occurred outside the CTV RTOG involved the proximal common iliac (19.3%) and lower periaortic nodes (19.3%) up to L2–L3. Conclusion: 3D mapping of nodal relapses evaluated with FCH PET/CT suggests that with IMRT the upper field limit of pelvic radiotherapy could be extended to L2–L3 safely to cover 95% of nodal stations at risk of an occult relapse

  1. Co-expression of GAD67 and choline acetyltransferase in neurons in the mouse spinal cord: A focus on lamina X.

    Science.gov (United States)

    Gotts, Jittima; Atkinson, Lucy; Yanagawa, Yuchio; Deuchars, Jim; Deuchars, Susan A

    2016-09-01

    Lamina X of the spinal cord is a functionally diverse area with roles in locomotion, autonomic control and processing of mechano and nociceptive information. It is also a neurochemically diverse region. However, the different populations of cells in lamina X remain to be fully characterised. To determine the co-localisation of the enzymes responsible for the production of GABA and acetylcholine (which play major roles in the spinal cord) in lamina X of the adult and juvenile mouse, we used a transgenic mouse expressing green fluorescent protein (GFP) in glutamate decarboxylase 67 (GAD67) neurons, combined with choline acetyltransferase (ChAT) immunohistochemistry. ChAT-immunoreactive (IR) and GAD67-GFP containing neurons were observed in lamina X of both adult and juvenile mice and in both age groups a population of cells containing both ChAT-IR and GAD67-GFP were observed in lumbar, thoracic and cervical spinal cord. Such dual labelled cells were predominantly located ventral to the central canal. Immunohistochemistry for vesicular acetylcholine transporter (VAChT) and GAD67 revealed a small number of double labelled terminals located lateral, dorsolateral and ventrolateral to the central canal. This study therefore describes in detail a population of ChAT-IR/GAD67-GFP neurons predominantly ventral to the central canal of the cervical, thoracic and lumbar spinal cord of adult and juvenile mice. These cells potentially correspond to a sub-population of the cholinergic central canal cluster cells which may play a unique role in controlling spinal cord circuitry. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Prognostic value of 18F-choline PET/CT metabolic parameters in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide

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    Caroli, Paola; Fantini, Lorenzo; Celli, Monica; Paganelli, Giovanni; Matteucci, Federica [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine Unit, Meldola (Italy); De Giorgi, Ugo; Conteduca, Vincenza; Rossi, Lorena [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Department of Medical Oncology, Meldola (Italy); Scarpi, Emanuela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials Unit, Meldola (Italy); Moretti, Andrea; Galassi, Riccardo [Morgagni Pierantoni Hospital, Nuclear Medicine Unit, Forli (Italy); Bianchi, Emanuela [Infermi Hospital, Department of Medical Oncology, Rimini (Italy)

    2018-03-15

    The role of 18F-choline positron emission tomography/computed tomography (FCH-PET/CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) has been firmly established in recent years. We analyzed the prognostic value of functional parameters such as mean standardized uptake volume (SUVmean), maximum standardized uptake volume (SUVmax), metabolic total volume (MTV; the volume of interest consisting of all spatially connected voxels within a fixed threshold of 40% of the SUVmax), and total lesion activity (TLA: the product of MTV and mean standardized uptake value) estimated with FCH-PET/CT in mCRPC patients in progression after docetaxel and treated with new antiandrogen receptor therapies, abiraterone or enzalutamide. We retrospectively studied 94 mCRPC patients, mean age 74 years (range 42-90), previously treated with docetaxel who were treated with either abiraterone (n = 52) or enzalutamide (n = 42). An FCH-PET/CT was performed at baseline, and patients were evaluated on a monthly basis for serological PSA response and every 3 months for radiological response. We measured MTV, SUVmean, SUVmax and TLA for each lesion and analyzed the sum of MTV (SMTV), SUVmean (SSUVmean), SUVmax (SSUVmax) and TLA (STLA) values for a maximum of 20 lesions. Univariate analysis was used to correlate these data with PFS and OS. We observed a median SMTV of 130 cm{sup 3}, median SSUVmax of 106.5 and a median STLA of 495,070. All of these parameters were significant for PFS and OS in univariate analysis, while only STLA was significant for PFS and OS in multivariate analysis after adjusting for lesion and age (p < 0.0001 and p = 0.001, respectively). Baseline PSA values maintained a certain reliability for OS (p = 0.034). Semiquantitative parameters of FCH-PET/CT play a prognostic role in mCRCP patients treated with abiraterone or enzalutamide. (orig.)

  3. Increasing proportions of tyrosine hydroxylase-immunoreactive interneurons colocalize with choline acetyltransferase or vasoactive intestinal peptide in the developing rat cerebral cortex

    Science.gov (United States)

    Asmus, Stephen E.; Cocanougher, Benjamin T.; Allen, Donald L.; Boone, John B.; Brooks, Elizabeth A.; Hawkins, Sarah M.; Hench, Laura A.; Ijaz, Talha; Mayfield, Meredith N.

    2011-01-01

    Cortical interneurons are critical for information processing, and their dysfunction has been implicated in neurological disorders. One subset of this diverse cell population expresses tyrosine hydroxylase (TH) during postnatal rat development. Cortical TH-immunoreactive neurons appear at postnatal day (P) 16. The number of TH cells sharply increases between P16 and P20 and subsequently decreases to adult values. The absence of apoptotic markers in these cells suggests that the reduction in cell number is not due to cell death but is due to a decline in TH production. Cortical TH cells lack all additional catecholaminergic enzymes, and many coexpress GABA and calretinin, but little else is known about their phenotype or function. Because interneurons containing choline acetyltransferase (ChAT) or vasoactive intestinal peptide (VIP) share characteristics with cortical TH neurons, the coexpression of TH with ChAT or VIP was examined throughout the neocortex at P16, P20, and P30. The proportions of TH cell profiles double-labeled for ChAT or VIP significantly increased between P16 and P30. Based on their proximity to blood vessels, intrinsic cholinergic and VIPergic cells have been hypothesized to regulate cortical microcirculation. Labeling with the gliovascular marker aquaporin-4 revealed that at least half of the TH cells were apposed to microvessels at these ages, and many of these cells contained ChAT or VIP. Cortical TH neurons did not coproduce nitric oxide synthase. These results suggest that increasing proportions of cortical TH neurons express ChAT or VIP developmentally and that a subset of these TH neurons may regulate local blood flow. PMID:21295554

  4. Dietary Oleate Has Beneficial Effects on Every Step of Non-Alcoholic Fatty Liver Disease Progression in a Methionine- and Choline-Deficient Diet-Fed Animal Model

    Directory of Open Access Journals (Sweden)

    Ji Young Lee

    2011-10-01

    Full Text Available BackgroundNon-alcoholic fatty liver disease (NAFLD is increasingly recognized as a major cause of liver-related morbidity and mortality. The underlying mechanisms of disease progression remain poorly understood, and primary therapy of NAFLD is not yet established. We investigated the effects of dietary oleate on the development and progression of NAFLD in a methionine- and choline-deficient (MCD diet-fed animal model.MethodsA total of 30 C57BL/6J mice were randomly divided into three groups (n=10 in each group and fed various experimental diets for four weeks: chow, MCD diet, or OMCD (MCD diet with oleate, 0.5 mg/g/day. Liver samples were examined for steatohepatitis and fibrosis parameters and associated genes.ResultsAdditional dietary oleate dramatically reduced MCD diet-induced hepatic steatosis. Hepatic carbohydrate responsive element-binding protein was overexpressed in MCD diet-fed mice, and dietary oleate prevented this overexpression (P<0.001. Dietary oleate partially prevented MCD diet-induced serum level increases in aspartate aminotransferase and alanine aminotransferase (P<0.001, respectively. The mRNA expressions of hepatic monocyte chemoattractant protein 1, tumor necrosis factor-α and matrix metalloproteinase-9 were increased in MCD diet-fed mice, and this overexpression of inflammatory molecules was prevented by dietary oleate (P<0.001. Hepatic pericellular fibrosis was observed in MCD diet-fed mice, and dietary oleate prevented this fibrosis. Altogether, dietary oleate prevented MCD diet-induced hepatic steatosis, inflammation and fibrosis.ConclusionDietary oleate has beneficial effects in every step of NAFLD development and progression and could be a nutritional option for NAFLD prevention and treatment.

  5. Standardized Salvia miltiorrhiza Extract Suppresses Hepatic Stellate Cell Activation and Attenuates Steatohepatitis Induced by a Methionine-Choline Deficient Diet in Mice

    Directory of Open Access Journals (Sweden)

    Hak Sung Lee

    2014-06-01

    Full Text Available The aim of this study was to examine the effect of standardized extract of Salvia miltiorrhiza (SME on gene and protein expression of non-alcoholic steatohepatitis (NASH-related factors in activated human hepatic stellate cells (HSC, and in mice with steatohepatitis induced by a methionine-choline deficient (MCD diet. Male C57BL/6J mice were placed on an MCD or control diet for 8 weeks and SME (0, 0.1, 0.5 and 1 mg/kg body weight was administered orally every other day for 4 or 6 weeks. HSCs from the LX-2 cell line were treated with transforming growth factor β-1 (TGF-β1 or TGF-β1 plus SME (0.1–10 μg/mL. To investigate the effect of SME on reactive oxygen species (ROS-induced condition, LX-2 cells were treated with hydrogen peroxide (H2O2 or H2O2 plus SME (0.1–100 μg/mL. MCD administration for 12 weeks increased mRNA expression of tumor necrosis factor (TNF-α, TGF-β1, interleukin-1β (IL-1β, C-reactive protein (CRP, α-smooth muscle actin (α-SMA, type I collagen, matrix metalloproteinase-2 (MMP-2 and MMP-9. TGF-β1-induced LX-2 cells exhibited similar gene expression patterns. SME treatment significantly reduced the mRNA and protein expression of NASH-related factors in the mouse model and HSCs. Histopathological liver analysis showed improved non-alcoholic fatty liver disease (NAFLD activity and fibrosis score in SME-treated mice. The in vivo studies showed that SME had a significant effect at low doses. These results suggest that SME might be a potential therapeutic candidate for NAFLD treatment.

  6. A silk peptide fraction restores cognitive function in AF64A-induced Alzheimer disease model rats by increasing expression of choline acetyltransferase gene

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Yeseul [College of Veterinary Medicine, Veterinary Medical Center, Chungbuk National University, Cheongju (Korea, Republic of); Lee, Sang Hoon [Department of Food Science and Technology, Chungbuk National University, Cheongju (Korea, Republic of); Jang, Su Kil [Division of Marine Molecular Biotechnology, Gangneung-Wonju National University, Gangneung (Korea, Republic of); Guo, Haiyu; Ban, Young-Hwan; Park, Dongsun [College of Veterinary Medicine, Veterinary Medical Center, Chungbuk National University, Cheongju (Korea, Republic of); Jang, Gwi Yeong; Yeon, Sungho [Department of Food Science and Technology, Chungbuk National University, Cheongju (Korea, Republic of); Lee, Jeong-Yong [Worldway Co., Ltd., Sejong (Korea, Republic of); Choi, Ehn-Kyoung [College of Veterinary Medicine, Veterinary Medical Center, Chungbuk National University, Cheongju (Korea, Republic of); Joo, Seong Soo [Division of Marine Molecular Biotechnology, Gangneung-Wonju National University, Gangneung (Korea, Republic of); Jeong, Heon-Sang, E-mail: hsjeong@cbu.ac.kr [Department of Food Science and Technology, Chungbuk National University, Cheongju (Korea, Republic of); Kim, Yun-Bae, E-mail: solar93@cbu.ac.kr [College of Veterinary Medicine, Veterinary Medical Center, Chungbuk National University, Cheongju (Korea, Republic of)

    2017-01-01

    This study investigated the effects of a silk peptide fraction obtained by incubating silk proteins with Protease N and Neutrase (SP-NN) on cognitive dysfunction of Alzheimer disease model rats. In order to elucidate underlying mechanisms, the effect of SP-NN on the expression of choline acetyltransferase (ChAT) mRNA was assessed in F3.ChAT neural stem cells and Neuro2a neuroblastoma cells; active amino acid sequence was identified using HPLC-MS. The expression of ChAT mRNA in F3.ChAT cells increased by 3.79-fold of the control level by treatment with SP-NN fraction. The active peptide in SP-NN was identified as tyrosine-glycine with 238.1 of molecular weight. Male rats were orally administered with SP-NN (50 or 300 mg/kg) and challenged with a cholinotoxin AF64A. As a result of brain injury and decreased brain acetylcholine level, AF64A induced astrocytic activation, resulting in impairment of learning and memory function. Treatment with SP-NN exerted recovering activities on acetylcholine depletion and brain injury, as well as cognitive deficit induced by AF64A. The results indicate that, in addition to a neuroprotective activity, the SP-NN preparation restores cognitive function of Alzheimer disease model rats by increasing the release of acetylcholine. - Highlights: • Cognition-enhancing effects of SP-NN, a silk peptide preparation, were investigated. • SP-NN enhanced ChAT mRNA expression in F3.ChAT neural stem cells and Neuro-2a neuroblastoma cells. • Active molecule was identified as a dipeptide composed of tyrosine-glycine. • SP-NN reversed cognitive dysfunction elicited by AF64A. • Neuroprotection followed by increased acetylcholine level was achieved with SP-NN.

  7. Assessment of Lymph Nodes and Prostate Status Using Early Dynamic Curves with (18)F-Choline PET/CT in Prostate Cancer.

    Science.gov (United States)

    Mathieu, Cédric; Ferrer, Ludovic; Carlier, Thomas; Colombié, Mathilde; Rusu, Daniela; Kraeber-Bodéré, Françoise; Campion, Loic; Rousseau, Caroline

    2015-01-01

    Dynamic image acquisition with (18)F-Choline [fluorocholine (FCH)] PET/CT in prostate cancer is mostly used to overcome the bladder repletion, which could obstruct the loco-regional analysis. The aim of our study was to analyze early dynamic FCH acquisitions to define pelvic lymph node or prostate pathological status. Retrospective analysis was performed on 39 patients for initial staging (n = 18), or after initial treatment (n = 21). Patients underwent 10-min dynamic acquisitions centered on the pelvis, after injection of 3-4 MBq/kg of FCH. Whole-body images were acquired about 1 h after injection using a PET/CT GE Discovery LS (GE-LS) or Siemens Biograph mCT (mCT). Maximum and mean SUV according to time were measured on nodal and prostatic lesions. SUVmean was corrected for partial volume effect (PVEC) with suitable recovery coefficients. The status of each lesion was based on histological results or patient follow-up (>6 months). A Mann-Whitney test and ANOVA were used to compare mean and receiver operating characteristic (ROC) curve analysis. The median PSA was 8.46 ng/mL and the median Gleason score was 3 + 4. Ninety-two lesions (43 lymph nodes and 49 prostate lesions) were analyzed, including 63 malignant lesions. In early dynamic acquisitions, the maximum and mean SUV were significantly higher, respectively, on mCT and GE-LS, in malignant versus benign lesions (p dynamic imaging using PET/CT FCH allowed prostate cancer detection in situations where proof of malignancy is difficult to obtain.

  8. Feasibility of TCP-based dose painting by numbers applied to a prostate case with 18F-choline PET imaging

    International Nuclear Information System (INIS)

    Dirscherl, Thomas; Bogner, Ludwig; Rickhey, Mark

    2012-01-01

    Introduction: A biologically adaptive radiation treatment method to maximize the TCP is shown. Functional imaging is used to acquire a heterogeneous dose prescription in terms of Dose Painting by Numbers and to create a patient-specific IMRT plan. Method and Materials: Adapted from a method for selective dose escalation under the guidance of spatial biology distribution, a model, which translates heterogeneously distributed radiobiological parameters into voxelwise dose prescriptions, was developed. At the example of a prostate case with 18 F-choline PET imaging, different sets of reported values for the parameters were examined concerning their resulting range of dose values. Furthermore, the influence of each parameter of the linear-quadratic model was investigated. A correlation between PET signal and proliferation as well as cell density was assumed. Using our in-house treatment planning software Direct Monte Carlo Optimization (DMCO), a treatment plan based on the obtained dose prescription was generated. Gafchromic EBT films were irradiated for evaluation. Results: When a TCP of 95% was aimed at, the maximal dose in a voxel of the prescription exceeded 100 Gy for most considered parameter sets. One of the parameter sets resulted in a dose range of 87.1 Gy to 99.3 Gy, yielding a TCP of 94.7%, and was investigated more closely. The TCP of the plan decreased to 73.5% after optimization based on that prescription. The dose difference histogram of optimized and prescribed dose revealed a mean of -1.64 Gy and a standard deviation of 4.02 Gy. Film verification showed a reasonable agreement of planned and delivered dose. Conclusion: If the distribution of radiobiological parameters within a tumor is known, this model can be used to create a dose-painting by numbers plan which maximizes the TCP. It could be shown, that such a heterogeneous dose distribution is technically feasible. (orig.)

  9. Generation patterns of four groups of cholinergic neurons in rat cervical spinal cord: a combined tritiated thymidine autoradiographic and choline acetyltransferase immunocytochemical study

    International Nuclear Information System (INIS)

    Phelps, P.E.; Barber, R.P.; Vaughn, J.E.

    1988-01-01

    This report examines the generation of cholinergic neurons in the spinal cord in order to determine whether the transmitter phenotype of neurons is associated with specific patterns of neurogenesis. Previous immunocytochemical studies identified four groups of choline acetyltransferase (ChAT)-positive neurons in the cervical enlargement of the rat spinal cord. These cell groups vary in both somatic size and location along the previously described ventrodorsal neurogenic gradient of the spinal cord. Thus, large (and small) motoneurons are located in the ventral horn, medium-sized partition cells are found in the intermediate gray matter, small central canal cluster cells are situated within lamina X, and small dorsal horn neurons are scattered predominantly through laminae III-V. The relationships among the birthdays of these four subsets of cholinergic neurons have been examined by combining 3H-thymidine autoradiography and ChAT immunocytochemistry. Embryonic day 11 was the earliest time that neurons were generated within the cervical enlargement. Large and small ChAT-positive motoneurons were produced on E11 and 12, with 70% of both groups being born on E11. ChAT-positive partition cells were produced between E11 and 13, with their peak generation occurring on E12. Approximately 70% of the cholinergic central canal cluster and dorsal horn cells were born on E13, and the remainder of each of these groups was generated on E14. Other investigators have shown that all neurons within the rat cervical spinal cord are produced in a ventrodorsal sequence between E11 and E16. In contrast, ChAT-positive neurons are born only from E11 to E14 and are among the earliest cells generated in the ventral, intermediate, and dorsal subdivisions of the spinal cord

  10. Modulatory role of Co-enzyme Q10 on methionine and choline deficient diet-induced non-alcoholic steatohepatitis (NASH) in albino rats.

    Science.gov (United States)

    Saleh, Dalia O; Ahmed, Rania F; Amin, Mohamed M

    2017-03-01

    The present study aimed to evaluate the hepato-protective and neuro-protective activity of Co-enzyme Q10 (CoQ10) on non-alcoholic steatohepatitis (NASH) in albino rats induced by methionine and choline-deficient (MCD) diet. Rats were fed an MCD diet for 8 weeks to induce non-alcoholic steatohepatitis. CoQ10 (10 mg/(kg·day) -1 ) was orally administered for 2 consecutive weeks. Twenty-four hours after the last dose of the drug, the behavioral test, namely the activity cage test, was performed and the activity counts were recorded. Serum alanine transaminase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, total/direct bilirubin, and albumin were valued to assess liver function. Moreover, hepatic cytokines interleukin-6 as well as its modulator nuclear factor kappa-light-chain-enhancer of activated B cells were determined. In addition, brain biomarkers, viz ammonia, nitric oxide, and brain-derived neurotrophic factor (BDNF), were measured as they are reliable indices to assess brain damage. Histopathological and immunohistochemical examination of brain proliferating cell nuclear antigen in brain and liver tissues were also evaluated. Results revealed that MCD-induced NASH showed impairment in the liver functions with an increase in the liver inflammatory markers. Moreover, NASH resulted in pronounced brain dysfunction as evidenced by hyper-locomotor activity, a decrease in the BDNF level, as well as an increase in the brain nitric oxide and ammonia contents. Oral treatment of MCD-diet-fed rats with CoQ10 for 14 days showed a marked improvement in all the assigned parameters. Finally, it can be concluded that CoQ10 has a hepatoprotective and neuroprotective role in MCD-diet-induced NASH in rats.

  11. Oral administration of choline does not affect metabolic characteristics of gliomas and normal-appearing white matter, as detected with single-voxel 1H-MRS at 1.5 T

    International Nuclear Information System (INIS)

    Chernov, Mikhail F.; Iseki, Hiroshi; Takakura, Kintomo; Muragaki, Yoshihiro; Maruyama, Takashi; Ono, Yuko; Usukura, Masao; Yoshida, Shigetoshi; Nakamura, Ryoichi; Kubo, Osami; Hori, Tomokatsu

    2009-01-01

    The present study was done for evaluation of the possible influence of the oral administration of choline on metabolic characteristics of gliomas detected with proton magnetic resonance spectroscopy ( 1 H-MRS). Thirty patients (22 men and eight women; mean age 38±15 years) with suspicious intracranial gliomas underwent single-voxel long-echo (TR 2,000 ms, TE 136 ms, 128-256 acquisitions) 1 H-MRS of the tumor, peritumoral brain tissue, and distant normal-appearing white matter before and several hours (median, 3 h; range, 1.2-3.7 h) after ingestion of choline with prescribed dose of 50 mg/kg (median actual dose, 52 mg/kg; range, 48-78 mg/kg). Investigations were done using 1.5 T clinical magnetic resonance imager. The volume of the rectangular 1 H-MRS voxel was either 3.4 or 8 cm 3 . At the time of both spectroscopic examinations, similar voxels' positioning and size and technical parameters of 1 H-MRS were used. Surgery was done in 27 patients within 1 to 68 days thereafter. In all cases, more than 80% resection of the neoplasm was attained. There were 12 low-grade gliomas and 15 high-grade gliomas. MIB-1 index varied from 0% to 51.7% (median, 13.8%). Statistical analysis did not disclose significant differences of any investigated metabolic parameter of the tumor, peritumoral brain tissue and distant normal-appearing white matter between two spectroscopic examinations. Single-voxel 1 H-MRS at 1.5 T could not detect significant changes of the metabolic characteristics of gliomas, peritumoral brain tissue, and distant normal-appearing white matter after oral administration of choline. (orig.)

  12. 18F-Choline Positron Emission Tomography/Computed Tomography–Driven High-Dose Salvage Radiation Therapy in Patients With Biochemical Progression After Radical Prostatectomy: Feasibility Study in 60 Patients

    International Nuclear Information System (INIS)

    D'Angelillo, Rolando M.; Sciuto, Rosa; Ramella, Sara; Papalia, Rocco; Jereczek-Fossa, Barbara A.; Trodella, Luca E.; Fiore, Michele; Gallucci, Michele; Maini, Carlo L.; Trodella, Lucio

    2014-01-01

    Purpose: To retrospectively review data of a cohort of patients with biochemical progression after radical prostatectomy, treated according to a uniform institutional treatment policy, to evaluate toxicity and feasibility of high-dose salvage radiation therapy (80 Gy). Methods and Materials: Data on 60 patients with biochemical progression after radical prostatectomy between January 2009 and September 2011 were reviewed. The median value of prostate-specific antigen before radiation therapy was 0.9 ng/mL. All patients at time of diagnosis of biochemical recurrence underwent dynamic 18 F-choline positron emission tomography/computed tomography (PET/CT), which revealed in all cases a local recurrence. High-dose salvage radiation therapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT-positive area. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events, version 3.0, scale. Results: Treatment was generally well tolerated: 54 patients (90%) completed salvage radiation therapy without any interruption. Gastrointestinal grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 genitourinary toxicity. No grade 4 acute toxicity events were recorded. Only 1 patient (1.7%) experienced a grade 2 gastrointestinal late toxicity. With a mean follow-up of 31.2 months, 46 of 60 patients (76.6%) were free of recurrence. The 3-year biochemical progression-free survival rate was 72.5%. Conclusions: At early follow-up, 18 F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity

  13. Variation of betaine, N,N-dimethylglycine, choline, glycerophosphorylcholine, taurine and trimethylamine-N-oxide in the plasma and urine of overweight people with type 2 diabetes over a two-year period.

    Science.gov (United States)

    McEntyre, Christopher J; Lever, Michael; Chambers, Stephen T; George, Peter M; Slow, Sandy; Elmslie, Jane L; Florkowski, Christopher M; Lunt, Helen; Krebs, Jeremy D

    2015-05-01

    Plasma betaine concentrations and urinary betaine excretions have high test-retest reliability. Abnormal betaine excretion is common in diabetes. We aimed to confirm the individuality of plasma betaine and urinary betaine excretion in an overweight population with type 2 diabetes and compare this with the individuality of other osmolytes, one-carbon metabolites and trimethylamine-N-oxide (TMAO), thus assessing their potential usefulness as disease markers. Urine and plasma were collected from overweight subjects with type 2 diabetes at four time points over a two-year period. We measured the concentrations of the osmolytes: betaine, glycerophosphorylcholine (GPC) and taurine, as well as TMAO, and the one-carbon metabolites, N,N-dimethylglycine (DMG) and free choline. Samples were measured using tandem mass spectrometry (LC-MS/MS). Betaine showed a high degree of individuality (or test-retest reliability) in the plasma (index of individuality = 0.52) and urine (index of individuality = 0.45). Betaine in the plasma had positive and negative log-normal reference change values (RCVs) of 54% and -35%, respectively. The other osmolytes, taurine and GPC were more variable in the plasma of individuals compared to the urine. DMG and choline showed high individuality in the plasma and urine. TMAO was highly variable in the plasma and urine (log-normal RCVs ranging from 403% to -80% in plasma). Betaine is highly individual in overweight people with diabetes. Betaine, its metabolite DMG, and precursor choline showed more reliability than the osmolytes, GPC and taurine. The low reliability of TMAO suggests that a single TMAO measurement has low diagnostic value. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  14. Effect on the content of n-acetylaspartate, total creatine, choline containing compounds, and lactate in the hippocampus of rats exposed to aromatic white spirit for three weeks measured by NMR spectroscopy

    DEFF Research Database (Denmark)

    Steensgaard, A; Ostergaard, G; Jensen, C V

    1996-01-01

    parameters in vivo, and to examine the same subjects repeatedly over time. NMR spectroscopy was used to study the effects of organic solvents in rats. Rats were exposed to 0, 400 ppm, or 800 ppm of aromatic white spirit 6 hr/day, 7 days/week for 3 weeks. During the first week, the rats showed signs...... of irritation of mucous membranes, and appeared to be sedated. Both types of effect gradually diminished during the second week. The rats were examined by single volume of interest (VOI) NMR spectroscopy. N-acetylaspartate, creatinine and phosphocreatinine, and choline containing compounds were measured...

  15. Influence of PSA, PSA velocity and PSA doubling time on contrast-enhanced 18F-choline PET/CT detection rate in patients with rising PSA after radical prostatectomy

    International Nuclear Information System (INIS)

    Schillaci, Orazio; Calabria, Ferdinando; Tavolozza, Mario; Caracciolo, Cristiana Ragano; Orlacchio, Antonio; Danieli, Roberta; Simonetti, Giovanni; Agro, Enrico Finazzi; Miano, Roberto

    2012-01-01

    To evaluate the accuracy of contrast-enhanced 18 F-choline PET/CT in restaging patients with prostate cancer after radical prostatectomy in relation to PSA, PSA velocity (PSAve) and PSA doubling time (PSAdt). PET/CT was performed in 49 patients (age range 58-87 years) with rising PSA (mean 4.13 ng/ml) who were divided in four groups according to PSA level: ≤1 ng/ml, 1 to ≤2 ng/ml, 2 to ≤4 ng/ml, and >4 ng/ml. PSAve and PSAdt were measured. PET and CT scans were interpreted separately and then together. PET/CT diagnosed relapse in 33 of the 49 patients (67%). The detection rates were 20%, 55%, 80% and 87% in the PSA groups ≤1, 1 to ≤2, 2 to ≤4 and >4 ng/ml, respectively. PET/CT was positive in 7 of 18 patients (38.9%) with a PSA ≤2 ng/ml, and in 26 of 31 (83.9%) with a PSA >2 ng/ml. PET/CT was positive in 7 of 25 patients (84%) with PSAdt ≤6 months, and in 12 of 24 patients (50%) with PSAdt >6 months, and was positive in 26 of 30 patients (86%) with a PSAve >2 ng/ml per year, and in 7 of 19 patients (36.8%) with PSAve ≤2 ng/ml per year. PET alone was positive in 31 of 49 patients (63.3%), and of these 31 patients, CT was negative in 14 but diagnosed bone lesions in 2 patients in whom PET alone was negative. CT with the administration of intravenous contrast medium did not provide any further information. Detection rate of 18 F-choline imaging is closely related to PSA and PSA kinetics. In particular, 18 F-choline PET/CT is recommended in patients with PSA >2 ng/ml, PSAdt ≤6 months and PSAve >2 ng/ml per year. CT is useful for detecting bone metastases that are not 18 F-choline-avid. The use of intravenous contrast agent seems unnecessary. (orig.)

  16. Influence of PSA, PSA velocity and PSA doubling time on contrast-enhanced {sup 18}F-choline PET/CT detection rate in patients with rising PSA after radical prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Schillaci, Orazio [University ' ' Tor Vergata' ' , Department of Biopathology and Diagnostic Imaging, Interventional, Rome (Italy); IRCCS Neuromed, Department of Nuclear Medicine and Molecular Imaging, Pozzilli (Italy); Calabria, Ferdinando [IRCCS Neuromed, Department of Nuclear Medicine and Molecular Imaging, Pozzilli (Italy); Tavolozza, Mario; Caracciolo, Cristiana Ragano; Orlacchio, Antonio; Danieli, Roberta; Simonetti, Giovanni [University ' ' Tor Vergata' ' , Department of Biopathology and Diagnostic Imaging, Interventional, Rome (Italy); Agro, Enrico Finazzi; Miano, Roberto [University Hospital ' ' Tor Vergata' ' , Department of Urology, Rome (Italy)

    2012-04-15

    To evaluate the accuracy of contrast-enhanced {sup 18}F-choline PET/CT in restaging patients with prostate cancer after radical prostatectomy in relation to PSA, PSA velocity (PSAve) and PSA doubling time (PSAdt). PET/CT was performed in 49 patients (age range 58-87 years) with rising PSA (mean 4.13 ng/ml) who were divided in four groups according to PSA level: {<=}1 ng/ml, 1 to {<=}2 ng/ml, 2 to {<=}4 ng/ml, and >4 ng/ml. PSAve and PSAdt were measured. PET and CT scans were interpreted separately and then together. PET/CT diagnosed relapse in 33 of the 49 patients (67%). The detection rates were 20%, 55%, 80% and 87% in the PSA groups {<=}1, 1 to {<=}2, 2 to {<=}4 and >4 ng/ml, respectively. PET/CT was positive in 7 of 18 patients (38.9%) with a PSA {<=}2 ng/ml, and in 26 of 31 (83.9%) with a PSA >2 ng/ml. PET/CT was positive in 7 of 25 patients (84%) with PSAdt {<=}6 months, and in 12 of 24 patients (50%) with PSAdt >6 months, and was positive in 26 of 30 patients (86%) with a PSAve >2 ng/ml per year, and in 7 of 19 patients (36.8%) with PSAve {<=}2 ng/ml per year. PET alone was positive in 31 of 49 patients (63.3%), and of these 31 patients, CT was negative in 14 but diagnosed bone lesions in 2 patients in whom PET alone was negative. CT with the administration of intravenous contrast medium did not provide any further information. Detection rate of {sup 18}F-choline imaging is closely related to PSA and PSA kinetics. In particular, {sup 18}F-choline PET/CT is recommended in patients with PSA >2 ng/ml, PSAdt {<=}6 months and PSAve >2 ng/ml per year. CT is useful for detecting bone metastases that are not {sup 18}F-choline-avid. The use of intravenous contrast agent seems unnecessary. (orig.)

  17. 18F-FDG versus 11C-choline PET/CT for the imaging of advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy: the time period during which PET/CT can reliably detect non-recurrence

    International Nuclear Information System (INIS)

    Ito, Kimiteru; Matsuda, Hiroshi; Yokoyama, Jyunkichi; Kubota, Kazuo; Morooka, Miyako; Shiibashi, Michio

    2010-01-01

    The purpose of this prospective study was to evaluate the usefulness of 18 F-fluorodeoxyglucose (FDG) and 11 C-choline positron emission tomography (PET)/computed tomography (CT) for detecting recurrences of advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy. Additionally, we surveyed the time period during which an effective negative predictive value could be maintained after the first follow-up PET/CT examination and estimated the optimal timing of a second PET/CT examination for detecting late recurrences. Fifty-three subjects (36 men and 17 women; mean age: 59.4±11.5 years) with advanced head and neck squamous cell carcinoma were recruited. Post-treatment 18 F-FDG PET/CT and 11 C-choline examinations were performed in all patients between 8 and 12 weeks after combined intra-arterial chemotherapy and radiotherapy. The PET/CT images were evaluated using a patient-based analysis and a lesion-based analysis. All of the patients were prospectively followed for at least 9 months after the post-treatment PET/CT examination, with surveillance using conventional images (including CT and/or MRI) and a physical examination performed every 3 months. Recurrences, as determined using the patient-based analysis, were eventually confirmed in 18, 6 and 5 patients at 3, 4-6 and 7-9 months after the post-treatment PET/CT examination, respectively. The sensitivity and specificity of the 18F-FDG PET/CT and the 11C-choline PET/CT examinations to predict recurrence within 3 months were higher (FDG: 89 and 91%; choline: 83 and 80%, respectively) than for recurrence detection 6 months (FDG: 67 and 90%; choline: 62 and 76%, respectively) and 9 months later (FDG: 59 and 92%; choline: 55 and 75%, respectively). The lesion-based analysis showed that the maximum standardized uptake value of 18 F-FDG and 11 C-choline in the recurrent lesions were correlated with each other, compared with their relation in scar tissues (R 2 = 0.492 and 0

  18. The role of 11C-choline positron emission tomography- computed tomography and videomediastinoscopy in the evaluation of diseases of middle mediastinum

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background Middle mediastinal masses comprise a wide variety of tumors but may also reflect lymphadenopathy, and thus remain an interesting diagnostic challenge. We performed positron emission tomography (PET) of mediastinal masses in order to evaluate the ability of PET to predict the malignancy of these tumors. We compared histologic findings, videomediastinoscopy, computed tomography (CT), and PET-CT in patients with mediastinal disease. Methods Thirty-two patients were evaluated with CT, PET-CT and videomediastionoscopy, and all studies were performed within four weeks in each patient. 11C-choline as a PET tracer was used to visualize masses. PET data were evaluated using the standardized uptake value (SUV) and were compared with pathologic data.Results There were 13 men and 19 women aged from 21 to 74 (mean 45.2) years. Among the patients with mediastinal diseases, sarcoidosis was diagnosed in 12 patients, tuberculosis in 5 patients, lymphoma in 5 patients, and noncaseating granulomata without classical "sarcoid" finding in 3 patients. N2 or N3 nodal metastasis was revealed in 6 of 7 patients who had non-small cell lung cancer or suspected lung cancer, and one was negative (the pathological diagnosis was reactive hyperplasia). The accuracies for correctly diagnosing mediastinal masses for CT, PET-CT and videomediastinoscopy were 38% (12/32), 63% (20/32), and 91% (29/32) respectively. The diagnostic accuracy of videomediastinoscopy was superior to that of PET-CT (χ2=11.130,P<0.001). The SUVs were similar among these diseases. On the other hand, if the diagnostic classification was benign vs malignancy, the accuracies for CT, PET-CT and videomediastinoscopy were 53% (17/32), 75% (24/32), 100% (32/32) respectively. The diagnostic accuracy of videomediastinoscopy was superior to that of PET-CT (χ2=22.042, P<0.001). The SUV of malignant lesions (6.9, 3.2-9.8; n=11) appeared to be higher than that of benign lesions (4.9, 2.9-8.3; n=21), however, this difference

  19. Chaperone-Mediated Regulation of Choline Acetyltransferase Protein Stability and Activity by HSC/HSP70, HSP90, and p97/VCP

    Directory of Open Access Journals (Sweden)

    Trevor M. Morey

    2017-12-01

    Full Text Available Choline acetyltransferase (ChAT synthesizes the neurotransmitter acetylcholine in cholinergic neurons, and mutations of this enzyme are linked to the neuromuscular disorder congenital myasthenic syndrome (CMS. One CMS-related mutation, V18M, reduces ChAT enzyme activity and cellular protein levels, and is located within a highly-conserved N-terminal proline-rich motif at residues 14PKLPVPP20. We showed previously that disruption of this proline-rich motif by either proline-to-alanine mutation (P17A/P19A or mutation of residue Val18 (V18M enhances ubiquitination and degradation of these mutant ChAT proteins expressed in cholinergic SN56 cells by an unknown mechanism. In this study, using proximity-dependent biotin identification (BioID, co-immunoprecipitation and in situ proximity-ligation assay (PLA, we identified the heat shock proteins (HSPs HSC/HSP70 and HSP90 as novel ChAT protein-interactors. These molecular chaperones are well-known for promoting the folding and stabilization of cellular proteins. Thus, we found that inhibition of HSPs by treatment of cells with either the HSC/HSP70 inhibitors 2-phenylethynesulfonamide (PES or VER-155008, or the HSP90 inhibitor 17-AAG reduced cellular ChAT activity and solubility, and enhanced the ubiquitination and proteasome-dependent loss of ChAT protein. Importantly, the effects of HSP inhibition were greater for mutant ChAT proteins (P17A/P19A-ChAT and CMS-related V18M- and A513T-ChAT compared to wild-type ChAT. HSPs can promote ubiquitination and degradation of terminally misfolded proteins through cooperative interaction with the E3 ubiquitin ligase CHIP/Stub1, and while we show that ChAT interacts with CHIP in situ, siRNA-mediated knock-down of CHIP had no effect on either wild-type or mutant ChAT protein levels. However, inhibition of the endoplasmic reticulum (ER- and HSP-associated co-chaperone p97/VCP prevented degradation of ubiquitinated ChAT. Together, these results identify novel mechanisms

  20. Toxicity and quality of life after choline-PET/CT directed salvage lymph node dissection and adjuvant radiotherapy in nodal recurrent prostate cancer

    International Nuclear Information System (INIS)

    Jilg, Cordula A; Leifert, Anja; Schnell, Daniel; Kirste, Simon; Volegova-Neher, Natalia; Schlager, Daniel; Wieser, Gesche; Henne, Karl; Schultze-Seemann, Wolfgang; Grosu, Anca-L; Rischke, Hans Christian

    2014-01-01

    In a previous study we demonstrated that, based on 11 C/ 18 F-choline positron emission tomography-computerized-tomography as a diagnostic tool, salvage lymph node dissection (LND) plus adjuvant radiotherapy (ART) is feasible for treatment of pelvic/retroperitoneal nodal recurrence of prostate cancer (PCa). However, the toxicity of this combined treatment strategy has not been systematically investigated before. The aim of the current study was to evaluate the acute and late toxicity and quality of life of ART after LND in pelvic/retroperitoneal nodal recurrent PCa. 43 patients with nodal recurrent PCa were treated with 46 LND followed by ART (mean 49.6 Gy total dose) at the sites of nodal recurrence. Toxicity of ART was analysed by physically examination (31/43, 72.1%), by requesting 15 frequent items of adverse events from the Common-Terminology-Criteria for Adverse Events Version 4.0-catalogue and by review of medical records. QLQ-C30 (EORTC quality of life assessment) and PR25 (prostate cancer module) questionnaires were used to investigate quality of life. Toxicity was evaluated before starting of ART, during ART (acute toxicity), after ART (mean 2.3 months) and at end of follow up (mean 3.2 years after end of ART) reflecting late toxicity. 71.7% (33/46) of 46 ART were treatment of pelvic, 10.9% (5/46) of retroperitoneal only and 28.3% (13/46) of pelvic and retroperitoneal regions. Overall 52 symptoms representing toxicities were observed before ART, 107 during ART, 88 after end of ART and 52 at latest follow up. Leading toxicities during ART were diarrhoea (19%, 20/107), urinary incontinence (16%, 17/107) and fatigue (16%, 17/107). The spectrum of late toxicities was almost equal to those before beginning of ART. No grade 3 adverse events or chronic lymphedema at extremities were observed. We observed no clear correlation between localisation of treated regions, technique of ART and frequency or severity of toxicities. Mean quality of life at final evaluation

  1. F18-choline PET/CT guided surgery in primary hyperparathyroidism when ultrasound and MIBI SPECT/CT are negative or inconclusive: the APACH1 study.

    Science.gov (United States)

    Quak, Elske; Blanchard, David; Houdu, Benjamin; Le Roux, Yannick; Ciappuccini, Renaud; Lireux, Barbara; de Raucourt, Dominique; Grellard, Jean-Michel; Licaj, Idlir; Bardet, Stéphane; Reznik, Yves; Clarisse, Bénédicte; Aide, Nicolas

    2018-04-01

    To evaluate the sensitivity of F18-choline (FCH) PET/CT for parathyroid adenoma detection prior to surgery in patients with primary hyperparathyroidism and negative or inconclusive cervical ultrasound and Tc99m-sestaMIBI SPECT/CT. We conducted a prospective bicentric study (NCT02432599). All patients underwent FCH PET/CT. The result was scored positive, inconclusive or negative. The number of uptakes and their sites were recorded. The FCH PET/CT result guided the surgical procedure (minimally invasive parathyroidectomy, bilateral cervical exploration, or other in case of multiple or ectopic foci). FCH PET/CT results were compared to the surgical and pathological findings and the follow-up. Twenty-five patients were included. Mean calcium and PTH levels prior to surgery were 2.76 ± 0.17 mmol/l and 94.8 ± 37.4 ng/l. Nineteen (76%) FCH PET/CTs were scored positive, 3 (12%) inconclusive and 3 (12%) negative, showing 21 cases of uniglandular disease, including 1 ectopic localization and 1 case of multiglandular (3 foci) disease. Mean lesion size was 13.1 ± 8.6 mm. Twenty-four patients underwent surgery. FCH PET/CT guided surgery in 22 (88%) patients, allowing for 17 minimally invasive parathyroidectomies, 1 bilateral cervical exploration for multifocality and 4 other surgical procedures. Two patients with negative FCH-PET/CT underwent bilateral cervical exploration. When dichotomizing the FCH PET/CT results, thereby classifying the inconclusive FCH PET/CT results as positive, the per lesion and per patient sensitivities were 91.3% (95%CI: 72.0-98.9) and 90.5% (95%CI: 69.6-98.8) and the corresponding positive predictive values were 87.5% (95%CI: 67.6-97.3) and 86.4% (95%CI: 65.1-97.1), respectively. Twenty-one (88%) patients were considered cured after surgery. Their mean calcium level after surgery was 2.36 ± 0.17 mmol/l. Preoperative FCH PET/CT has a high sensitivity and positive predictive value for parathyroid adenoma detection in patients

  2. Positron emission tomographic imaging with 11C-choline in differential diagnosis of head and neck tumors. Comparison with 18F-FDG PET

    International Nuclear Information System (INIS)

    Khan, N.; Oriuchi, Noboru; Ninomiya, Hiroshi; Higuchi, Tetsuya; Kamada, Hideo; Endo, Keigo

    2004-01-01

    The aim of this study was to evaluate the clinical value of positron emission tomography (PET) with 11 C-labeled choline (CHOL) for the differential diagnosis of malignant head and neck tumors from benign lesions as compared with 18 F-fluorodeoxyglucose PET. We studied 45 patients (28 males, 17 females, age range, 29-84 years) with suspected lesions in the head and neck region using both CHOL and FDG PET within a 2-week period on each patient. All patients fasted for at least 6 hours for both the CHOL and FDG studies. PET imaging was performed 5 min and 50-60 min after intravenous injection of CHOL and FDG, respectively. After data acquisition, PET images were corrected for attenuation, and the reconstructed images were analyzed by visual interpretation. Then, the standardized uptake value (SUV) was calculated for semiquantitative evaluation of tumor tracer uptake. Finally the results of PET scans were compared with the histological diagnoses from surgical specimens or biopsies. With CHOL PET, malignant tumors were correctly detected in 24 (96%) of 25 patients, and benign lesions in 14 (70%) of 20 patients with an accuracy of 84.4%. With FDG PET, malignancy was correctly diagnosed in 23 (92%) of 25 patients, and benign lesions in 13 (65%) of 20 patients resulting an accuracy of 80%. A significant positive correlation between CHOL and FDG SUVs was found for all lesions (r=0.677, p=0.004, n=45). Malignant tumors showed significantly higher tracer accumulation than the benign lesions in both CHOL and FDG studies (5.69±1.61, n=25 vs. 2.98±2.13, n=20, p<0.0001; 9.21±4.23, n=25 vs. 3.60±2.57, n=20, p<0.0001). The cutoff SUV for differentiating malignant and benign lesions was 3.5 for CHOL and 3.9 for FDG. CHOL showed slightly better differentiation between malignant and benign lesions than FDG although some overlap existed on both studies. But the difference was not statistically significant. The results of this study indicate that CHOL PET may be feasible clinically

  3. Bioethanol production from paperboard mill sludge using acid-catalyzed bio-derived choline acetate ionic liquid pretreatment followed by fermentation process

    International Nuclear Information System (INIS)

    Farghaly, Ahmed; Elsamadony, Mohamed; Ookawara, Shinichi; Tawfik, Ahmed

    2017-01-01

    Highlights: • Total reducing sugar concentration depends on [ChO][OAc] ionic liquid to biomass ratio. • Acid-catalyzed ionic liquid significantly enhance pretreatment process. • Prolonged pretreatment duration degraded sugars into furans compounds. • Maximum net energy of 5.36 ± 0.30 kJ/g PMS obtained by using acid catalyst IL. - Abstract: Paperboard mill sludge (PMS) composed of cellulose, hemicellulose, lignin and ash contents of 36.72 ± 2.81, 32.91 ± 1.75, 22.89 ± 0.56, and 7.48 ± 0.39%, respectively. Enzymatic hydrolysis process followed by fermentation of native PMS provided an ethanol yield of 0.36 ± 0.01 g/L which equivalent to net gain energy of −0.84 ± 0.03 kJ/g PMS . Choline acetate ionic liquid [Cho][OAc] IL was extensively used as a solvent for PMS to upgrade the performance. Pretreatment with [Cho][OAc] IL/PMS ratio of 10% (w/w) for 1.0 h, at a temperature of 120 °C exhibited hemicellulose and lignin removal efficiency of 5.05 ± 0.52 and 14.71 ± 1.22%, respectively with 89.19 ± 5.62% cellulose recovery. This corresponded to net gain energy of 0.60 ± 0.04 kJ/g PMS based on ethanol yield from enzymatic saccharification process which was quite low due to a limited hemicellulose removal and glucose yield of 24.1 ± 1.4 g/L. [Cho][OAc] IL/PMS ratio of 10% (w/w) supplemented with 1% (v/v) HCl substantially improved the removal efficiency of hemicellulose (36.38 ± 4.51%), lignin (17.42 ± 1.19%) and cellulose (82.17 ± 4.28%) which provided the maximum net energy of 5.36 ± 0.30 kJ/g PMS .

  4. F18-choline PET/CT guided surgery in primary hyperparathyroidism when ultrasound and MIBI SPECT/CT are negative or inconclusive. The APACH1 study

    Energy Technology Data Exchange (ETDEWEB)

    Quak, Elske; Lireux, Barbara; Bardet, Stephane [Francois Baclesse Cancer Centre, Department of Nuclear Medicine and Thyroid Unit, Caen (France); Blanchard, David; Raucourt, Dominique de [Francois Baclesse Cancer Centre, Department of Head and Neck Surgery, Caen (France); Houdu, Benjamin [University Hospital, Department of Nuclear Medicine, Caen (France); Le Roux, Yannick [University Hospital, Department of General and Endocrine Surgery, Caen (France); Ciappuccini, Renaud [Francois Baclesse Cancer Centre, Department of Nuclear Medicine and Thyroid Unit, Caen (France); Caen University, INSERM 1086 ANTICIPE, Caen (France); Grellard, Jean-Michel; Licaj, Idlir; Clarisse, Benedicte [Francois Baclesse Cancer Centre, Department of Clinical Research, Caen (France); Reznik, Yves [University Hospital, Department of Endocrinology, Caen (France); Aide, Nicolas [Francois Baclesse Cancer Centre, Department of Nuclear Medicine and Thyroid Unit, Caen (France); University Hospital, Department of Nuclear Medicine, Caen (France); Caen University, INSERM 1086 ANTICIPE, Caen (France)

    2018-04-15

    To evaluate the sensitivity of F18-choline (FCH) PET/CT for parathyroid adenoma detection prior to surgery in patients with primary hyperparathyroidism and negative or inconclusive cervical ultrasound and Tc99m-sestaMIBI SPECT/CT. We conducted a prospective bicentric study (NCT02432599). All patients underwent FCH PET/CT. The result was scored positive, inconclusive or negative. The number of uptakes and their sites were recorded. The FCH PET/CT result guided the surgical procedure (minimally invasive parathyroidectomy, bilateral cervical exploration, or other in case of multiple or ectopic foci). FCH PET/CT results were compared to the surgical and pathological findings and the follow-up. Twenty-five patients were included. Mean calcium and PTH levels prior to surgery were 2.76 ± 0.17 mmol/l and 94.8 ± 37.4 ng/l. Nineteen (76%) FCH PET/CTs were scored positive, 3 (12%) inconclusive and 3 (12%) negative, showing 21 cases of uniglandular disease, including 1 ectopic localization and 1 case of multiglandular (3 foci) disease. Mean lesion size was 13.1 ± 8.6 mm. Twenty-four patients underwent surgery. FCH PET/CT guided surgery in 22 (88%) patients, allowing for 17 minimally invasive parathyroidectomies, 1 bilateral cervical exploration for multifocality and 4 other surgical procedures. Two patients with negative FCH-PET/CT underwent bilateral cervical exploration. When dichotomizing the FCH PET/CT results, thereby classifying the inconclusive FCH PET/CT results as positive, the per lesion and per patient sensitivities were 91.3% (95%CI: 72.0-98.9) and 90.5% (95%CI: 69.6-98.8) and the corresponding positive predictive values were 87.5% (95%CI: 67.6-97.3) and 86.4% (95%CI: 65.1-97.1), respectively. Twenty-one (88%) patients were considered cured after surgery. Their mean calcium level after surgery was 2.36 ± 0.17 mmol/l. Preoperative FCH PET/CT has a high sensitivity and positive predictive value for parathyroid adenoma detection in patients with primary

  5. Elevation of liver endoplasmic reticulum stress in a modified choline-deficient l-amino acid-defined diet-fed non-alcoholic steatohepatitis mouse model.

    Science.gov (United States)

    Muraki, Yo; Makita, Yukimasa; Yamasaki, Midori; Amano, Yuichiro; Matsuo, Takanori

    2017-05-06

    Endoplasmic reticulum (ER) stress caused by accumulation of misfolded proteins is observed in several kinds of diseases. Since ER stress is reported to be involved in the progression of non-alcoholic steatohepatitis (NASH), highly sensitive and simple measurement methods are required for research into developing novel therapy for NASH. To investigate the involvement of ER stress in NASH pathogenesis in a mouse model, an assay for liver ER stress was developed using ER stress activated indicator-luciferase (ERAI-Luc) mice. To establish the assay method for detection of ER stress in the liver, tunicamycin (TM) (0.3 mg/kg i. p.) was administered to ERAI-Luc mice, and the luciferase activity was measured in ex vivo and in vivo. To evaluate ER stress in the NASH model, ERAI-Luc mice were fed a modified choline-deficient l-amino acid-defined (mCDAA) diet for 14 weeks. After measurement of ER stress by luminescence imaging, levels of liver lipids and pro-fibrotic and pro-inflammatory gene expression were measured as NASH-related indexes. In non-invasive whole-body imaging, TM elevated luciferase activity in the liver, induced by activation of ER stress. The highest luminescence in the liver was confirmed by ex vivo imaging of isolated tissues. In parallel with progression of NASH, elevated luminescence induced by ER stress in liver was observed in mCDAA diet-fed ERAI-Luc mice. Luciferase activity was significantly and positively correlated to levels of triglyceride and free cholesterol in the liver, as well as to the mRNA expression of type 1 collagen α1 chain and tumor necrosis factor α. These data indicated that the use of ERAI-Luc mice was effective in the detection of ER stress in the liver. Moreover, the NASH model using ERAI-Luc mice can be a useful tool to clarify the role of ER stress in pathogenesis of NASH and to evaluate effects of drugs targeted against ER stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. F18-choline PET/CT guided surgery in primary hyperparathyroidism when ultrasound and MIBI SPECT/CT are negative or inconclusive. The APACH1 study

    International Nuclear Information System (INIS)

    Quak, Elske; Lireux, Barbara; Bardet, Stephane; Blanchard, David; Raucourt, Dominique de; Houdu, Benjamin; Le Roux, Yannick; Ciappuccini, Renaud; Grellard, Jean-Michel; Licaj, Idlir; Clarisse, Benedicte; Reznik, Yves; Aide, Nicolas

    2018-01-01

    To evaluate the sensitivity of F18-choline (FCH) PET/CT for parathyroid adenoma detection prior to surgery in patients with primary hyperparathyroidism and negative or inconclusive cervical ultrasound and Tc99m-sestaMIBI SPECT/CT. We conducted a prospective bicentric study (NCT02432599). All patients underwent FCH PET/CT. The result was scored positive, inconclusive or negative. The number of uptakes and their sites were recorded. The FCH PET/CT result guided the surgical procedure (minimally invasive parathyroidectomy, bilateral cervical exploration, or other in case of multiple or ectopic foci). FCH PET/CT results were compared to the surgical and pathological findings and the follow-up. Twenty-five patients were included. Mean calcium and PTH levels prior to surgery were 2.76 ± 0.17 mmol/l and 94.8 ± 37.4 ng/l. Nineteen (76%) FCH PET/CTs were scored positive, 3 (12%) inconclusive and 3 (12%) negative, showing 21 cases of uniglandular disease, including 1 ectopic localization and 1 case of multiglandular (3 foci) disease. Mean lesion size was 13.1 ± 8.6 mm. Twenty-four patients underwent surgery. FCH PET/CT guided surgery in 22 (88%) patients, allowing for 17 minimally invasive parathyroidectomies, 1 bilateral cervical exploration for multifocality and 4 other surgical procedures. Two patients with negative FCH-PET/CT underwent bilateral cervical exploration. When dichotomizing the FCH PET/CT results, thereby classifying the inconclusive FCH PET/CT results as positive, the per lesion and per patient sensitivities were 91.3% (95%CI: 72.0-98.9) and 90.5% (95%CI: 69.6-98.8) and the corresponding positive predictive values were 87.5% (95%CI: 67.6-97.3) and 86.4% (95%CI: 65.1-97.1), respectively. Twenty-one (88%) patients were considered cured after surgery. Their mean calcium level after surgery was 2.36 ± 0.17 mmol/l. Preoperative FCH PET/CT has a high sensitivity and positive predictive value for parathyroid adenoma detection in patients with primary

  7. A simple, versatile, low-cost and remotely operated apparatus for [11C]acetate, [11C]choline, [11C]methionine and [11C]PIB synthesis

    International Nuclear Information System (INIS)

    Cheung Manki; Ho Chilai

    2009-01-01

    A simple, efficient and remotely operated synthesis apparatus for carrying out routine [ 11 C]carboxylation, on-column and bubbling [ 11 C]methylation was essential for reliable, day-to-day production of [ 11 C]-labelled PET radiopharmaceuticals. We developed an in-house apparatus specifically applied to the synthesis of [ 11 C]acetate, [ 11 C]choline, [ 11 C]methionine and 2-(4'-N-[ 11 C]methylaminophenyl)-6-hydroxybenzothiazole ([ 11 C]PIB), where high radiochemical purity (≥97%) and moderate radiochemical yields (18% for [ 11 C]PIB, 41-55% for the others) could be achieved. These findings provided evidence that this was a fast, versatile and reliable apparatus suitable for a PET/CT centre with limited financial budget and hot cell space for synthesis of [ 11 C]-labelled radiopharmaceuticals

  8. The Advantages of Human Milk Recognize the Spatiotemporal Locations of Toxins and Intelligently Bypass Them by Forming a Hummingbird-Like Hovering Neural Network Circuitry Based on an Organic Biomimetic Choline Acetyltransferase Memristor/Memcapacitor Prosthesis

    Directory of Open Access Journals (Sweden)

    E. T. CHEN

    2016-08-01

    Full Text Available We have demonstrated a unique approach to study human milk’s advantage in promoting and protecting infant early brain cognitive development by recognizing toxins and intelligently bypassing the toxin by forming high frequency oscillation (HFO in the brain circuitry when compared with organic cow milk samples based on an organic memristor/memcapacitor biomimetic Choline Acetyltransferase (CHAT neural network circuitry prosthesis along with a 3D Energy-sensory dynamic mapping method under antibody- free, radiolabeling-free, and reagent-less conditions. We also demonstrated cow milk is unfit for infant cognitive development, and it is actually harmful in terms of mutating infant brain synapse circuitry conformation, current flow direction, and energy output that lead to multiple Pathological High Frequency Oscillation (pHFO formations, and further, it led to sudden infant death syndrome (SIDS based on our prediction.

  9. Detection of related substances in polyene phosphatidyl choline extracted from soybean and in its commercial capsule by comprehensive supercritical fluid chromatography with mass spectrometry compared with HPLC with evaporative light scattering detection.

    Science.gov (United States)

    Jiang, Qikun; Liu, Wanjun; Li, Xiaoting; Zhang, Tianhong; Wang, Yongjun; Liu, Xiaohong

    2016-01-01

    Supercritical fluid chromatography with tandem mass spectrometry was used to comprehensively profile polyene phosphatidyl choline (PPC) extracted from soybean. We achieved an efficient chromatographic analysis using a BEH-2EP column (3 × 100 mm(2) , 1.7 μm) with a mobile phase consisting of CO2 and a cosolvent in gradient combination at a flow rate of 1.0 mL/min. The cosolvent consisted of methanol, acetonitrile, and water (containing 10 mM ammonium acetate and 0.2% formic acid). The total single-run time was 7 min. We used this method to accurately detect ten different phospholipids (PLs) during extraction. The limits of quantification for phosphatidyl choline, lyso-phosphatidylcholine (LPC), phosphatidic acid (PA), sphingomyelin, phosphatidyl glycerol, phosphatidyl inositol (PI), cholesterol, cardiolipin, phosphatidyl serine, and phosphatidyl ethanolamine (PE) were 20.6, 19.52, 1.21, 2.38, 0.50, 2.28, 54.3, 0.60, 0.65, and 4.85 ng/mL, respectively. However, adopting the high-performance liquid chromatography with evaporative light scattering detection method issued by the China Food and Drug Administration, only PA, LPC, PE, PI, and PPC could be analyzed accurately, and the limits of quantification were 33.89, 60.5, 30.3, 10.9, and 61.79 μg/mL, respectively. The total single-run time was at the least 20 min. Consequently, the supercritical fluid chromatography with tandem mass spectrometry method was more suitable for the analysis of related PLs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Comparison of [(11)C]Choline ([(11)C]CHO) and [(18)F]Bombesin (BAY 86-4367) as Imaging Probes for Prostate Cancer in a PC-3 Prostate Cancer Xenograft Model.

    Science.gov (United States)

    Schwarzenböck, Sarah Marie; Schmeja, Philipp; Kurth, Jens; Souvatzoglou, Michael; Nawroth, Roman; Treiber, Uwe; Kundt, Guenther; Berndt, Sandra; Graham, Keith; Senekowitsch-Schmidtke, Reingard; Schwaiger, Markus; Ziegler, Sibylle I; Dinkelborg, Ludger; Wester, Hans-Jürgen; Krause, Bernd Joachim

    2016-06-01

    Carbon-11- and fluorine-18-labeled choline derivatives are commonly used in prostate cancer imaging in the clinical setting for staging and re-staging of prostate cancer. Due to a limited detection rate of established positron emission tomography (PET) tracers, there is a clinical need for innovative tumor-specific PET compounds addressing new imaging targets. The aim of this study was to compare the properties of [(18)F]Bombesin (BAY 86-4367) as an innovative biomarker for prostate cancer imaging targeting the gastrin-releasing peptide receptor and [(11)C]Choline ([(11)C]CHO) in a human prostate tumor mouse xenograft model by small animal PET/X-ray computed tomography (CT). We carried out a dual-tracer small animal PET/CT study comparing [(18)F]Bombesin and [(11)C]CHO. The androgen-independent human prostate tumor cell line PC-3 was implanted subcutaneously in the flanks of nu/nu NMRI mice (n = 10) (PET/CT measurements of two [(11)C]Choline mice could not be analyzed due to technical reasons). [(18)F]Bombesin and [(11)C]CHO PET/CT imaging was performed about 3-4 weeks after the implantation of PC-3 cells on two separate days. After the intravenous tail vein injection of 14 MBq [(18)F]Bombesin and 37 MBq [(11)C]CHO, respectively, a dynamic study over 60 min was acquired in list mode using an Inveon animal PET/CT scanner (Siemens Medical Solutions). The sequence of [(18)F]Bombesin and [(11)C]CHO was randomized. Image analysis was performed using summed images as well as dynamic data. To calculate static and dynamic tumor-to-muscle (T/M), tumor-to-blood (T/B), liver-to-blood (L/B), and kidney-to-blood (K/B) ratios, 4 × 4 × 4 mm(3) volumes of interest (VOIs) of tumor, muscle (thigh), liver, kidney, and blood derived from transversal slices were used. The mean T/M ratio of [(18)F]Bombesin and [(11)C]CHO was 6.54 ± 2.49 and 1.35 ± 0.30, respectively. The mean T/B ratio was 1.83 ± 0.79 for [(18)F]Bombesin and 0.55 ± 0.10 for [(11)C

  11. Interaction between repressor Opi1p and ER membrane protein Scs2p facilitates transit of phosphatidic acid from the ER to mitochondria and is essential for INO1 gene expression in the presence of choline.

    Science.gov (United States)

    Gaspar, Maria L; Chang, Yu-Fang; Jesch, Stephen A; Aregullin, Manuel; Henry, Susan A

    2017-11-10

    In the yeast Saccharomyces cerevisiae , the Opi1p repressor controls the expression of INO1 via the Opi1p/Ino2p-Ino4p regulatory circuit. Inositol depletion favors Opi1p interaction with both Scs2p and phosphatidic acid at the endoplasmic reticulum (ER) membrane. Inositol supplementation, however, favors the translocation of Opi1p from the ER into the nucleus, where it interacts with the Ino2p-Ino4p complex, attenuating transcription of INO1 A strain devoid of Scs2p ( scs2 Δ) and a mutant, OPI1FFAT , lacking the ability to interact with Scs2p were utilized to examine the specific role(s) of the Opi1p-Scs2p interaction in the regulation of INO1 expression and overall lipid metabolism. Loss of the Opi1p-Scs2p interaction reduced INO1 expression and conferred inositol auxotrophy. Moreover, inositol depletion in strains lacking this interaction resulted in Opi1p being localized to sites of lipid droplet formation, coincident with increased synthesis of triacylglycerol. Supplementation of choline to inositol-depleted growth medium led to decreased TAG synthesis in all three strains. However, in strains lacking the Opi1p-Scs2p interaction, Opi1p remained in the nucleus, preventing expression of INO1 These data support the conclusion that a specific pool of phosphatidic acid, associated with lipid droplet formation in the perinuclear ER, is responsible for the initial rapid exit of Opi1p from the nucleus to the ER and is required for INO1 expression in the presence of choline. Moreover, the mitochondria-specific phospholipid, cardiolipin, was significantly reduced in both strains compromised for Opi1p-Scs2p interaction, indicating that this interaction is required for the transfer of phosphatidic acid from the ER to the mitochondria for cardiolipin synthesis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Plasma microRNAs are sensitive indicators of inter-strain differences in the severity of liver injury induced in mice by a choline- and folate-deficient diet

    International Nuclear Information System (INIS)

    Tryndyak, Volodymyr P.; Latendresse, John R.; Montgomery, Beverly; Ross, Sharon A.; Beland, Frederick A.; Rusyn, Ivan; Pogribny, Igor P.

    2012-01-01

    MicroRNAs (miRNAs) are a class of small, conserved, tissue-specific regulatory non-coding RNAs that modulate a variety of biological processes and play a fundamental role in the pathogenesis of major human diseases, including nonalcoholic fatty liver disease (NAFLD). However, the association between inter-individual differences in susceptibility to NAFLD and altered miRNA expression is largely unknown. In view of this, the goals of the present study were (i) to determine whether or not individual differences in the extent of NAFLD-induced liver injury are associated with altered miRNA expression, and (ii) assess if circulating blood miRNAs may be used as potential biomarkers for the noninvasive evaluation of the severity of NAFLD. A panel of seven genetically diverse strains of inbred male mice (A/J, C57BL/6J, C3H/HeJ, 129S/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ) were fed a choline- and folate-deficient (CFD) diet for 12 weeks. This diet induced liver injury in all mouse strains; however, the extent of NAFLD-associated pathomorphological changes in the livers was strain-specific, with A/J, C57BL/6J, and C3H/HeJ mice being the least sensitive and WSB/EiJ mice being the most sensitive. The morphological changes in the livers were accompanied by differences in the levels of hepatic and plasma miRNAs. The levels of circulating miR-34a, miR-122, miR-181a, miR-192, and miR-200b miRNAs were significantly correlated with a severity of NAFLD-specific liver pathomorphological features, with the strongest correlation occurring with miR-34a. These observations suggest that the plasma levels of miRNAs may be used as biomarkers for noninvasive monitoring the extent of NAFLD-associated liver injury and susceptibility to NAFLD. -- Highlights: ► Choline- and folate-deficiency induces a strain-specific fatty liver injury in mice. ► The extent of liver pathology was accompanied by the changes in microRNA expression. ► The levels of circulating microRNAs mirror the magnitude of

  13. Desempenho produtivo de tilápia do Nilo alimentada com níveis de colina na dieta - doi: 10.4025/actascianimsci.v32i2.8862 Growth performance of Nile tilapia fed graded choline levels in the diet - doi: 10.4025/actascianimsci.v32i2.8862

    Directory of Open Access Journals (Sweden)

    Igo Gomes Guimarães

    2010-07-01

    Full Text Available Este estudo foi realizado com o objetivo de avaliar o desempenho produtivo da tilápia do Nilo (Oreochromis niloticus alimentada com níveis de colina na dieta pelo período de 109 dias. Foram utilizados 192 alevinos com 4,0 ± 0,15 g de peso médio, distribuídos em 32 tanques-rede de 200 L, na densidade de seis peixes por tanque-rede, dispostos em aquários de 1.000 L. O delineamento experimental foi inteiramente casualizado com oito tratamentos e quatro repetições. As rações foram suplementadas com 0, 100, 200, 400, 600, 800, 1.000 e 1.200 mg de colina kg-1 de ração. Não foram observadas diferenças para ganho de peso, taxa de sobrevivência, conversão alimentar aparente, porcentagem de extrato etéreo do filé e do fígado, índice hepatossomático e concentração de lipídeos no plasma. Concluiu-se que os diferentes níveis de colina não melhoraram o desempenho produtivo dos peixes nestas condições, pois a dieta basal supostamente supriu a exigência do peixe para colina.A 109-day feeding trial was undertaken aiming to evaluate the growth performance of Nile tilapia fed graded choline levels. One hundred and ninety-two (initial weight 4.0 ± 0.15 g fingerlings were distributed into 32 net cages (200 L each, four cages per treatment and six fish per cage, placed in eight 1000L aquaria in a closed recirculation system. The treatments were assigned to the tanks comprising eight treatments and four replications arranged in a completely randomized experimental design. Diets were supplemented with choline chloride to provide 100, 200, 400, 600, 800, 1000, 1200 mg of choline per kg of feed and an unsupplemented diet. No significant differences were observed in growth performance, survival, apparent feed conversion, liver and fillet ether extract, hepatosomatic index and plasma lipid concentration, among treatments. Choline levels did not improve growth performance, possibly because the amount of choline in the diet had already met fish

  14. Choline acetyltransferase and TrkA expression, as well as the improvement in cognition produced by E2 and P4 in ovariectomized rats, are blocked by ICI 182 780 and RU486.

    Science.gov (United States)

    Espinosa-Raya, Judith; Cruz-Raya, Ulises; López-Martínez, Margarita; Picazo, Ofir

    2018-01-09

    Treatment with 17-β estradiol and progesterone improves the performance of ovariectomized rats in an autoshaping learning task, representing cognitive improvement. To test whether this is attributable to genomic mechanisms, the antiestrogen ICI 182 780 or antiprogesterone RU486 was injected into ovariectomized animals primed previously with estrogen or progesterone, respectively. Compared with the vehicle control, each hormone administered alone produced an elevated expression of choline acetyltransferase and TrkA, along with an improvement in performance on the behavioral test. E2+ICI reverted the increase in these two proteins. However, RU alone elicited higher ChAT expression. With this exception, there was a clear linear regression between the number of conditioned responses and the level of ChAT and TrkA in the basal forebrain. The results suggest that TrkA may be more important than ChAT for regulating autoshaping learning tasks, and that genomic mechanisms in the basal forebrain could possibly underlie hormonal improvement of cognition.

  15. Electrochemical study and recovery of Pb using 1:2 choline chloride/urea deep eutectic solvent: A variety of Pb species PbSO4, PbO2, and PbO exhibits the analogous thermodynamic behavior

    International Nuclear Information System (INIS)

    Liao, Yu-Shun; Chen, Po-Yu; Sun, I-Wen

    2016-01-01

    Water-insoluble PbSO 4 , PbO 2 , and PbO are fairly soluble in choline chloride/urea deep eutectic solvent (ChCl/urea DES) in 1:2 molar ratio. Very interestingly, solution prepared from PbO 2 exhibits the almost identical electrochemical behavior as those from PbSO 4 and PbO, indicating that Pb(II) is formed in the DES regardless of what Pb compound is introduced. The electrochemical reduction of the Pb(II) species is determined as an irreversible process, and involves the three-dimensional (3D) instantaneous nucleation with diffusion-controlled growth. From the dependence of the diffusion coefficient on temperature, the activation energy for diffusion of PbSO 4 and PbO 2 is determined to be 33.7 and 34.1 kJ mol −1 , respectively. Electrodeposition of Pb was achieved potentiostatically and galvanostatically. The surface morphology of Pb deposits significantly depends on the applied potential and current. The coulombic efficiency of Pb electrodeposition is higher than 90%. Electrodeposition of Pb from a wet DES containing a mixture of three different Pb sources is also investigated. The XRD analysis confirmed that the electrodeposits consisted of metallic Pb.

  16. Determination of As, Cr, Mo, Sb, Se and V in agricultural soil samples by inductively coupled plasma optical emission spectrometry after simple and rapid solvent extraction using choline chloride-oxalic acid deep eutectic solvent.

    Science.gov (United States)

    Matong, Joseph M; Nyaba, Luthando; Nomngongo, Philiswa N

    2017-01-01

    A rapid, simple and green ultrasound-assisted extraction method using deep eutectic solvents (DES) for extraction of As, Cr, Mo, Sb, Se and V in soil samples, has been developed. Choline chloride-oxalic acid based DES was used as a solvent. The target analytes were subsequently quantified using inductively coupled plasma optical emission spectrometer (ICP OES). The parameters that affect the extraction of the target analytes was optimized using standard reference material of San Joaquin soil (SRM 2709a). In the optimization step, a two-level full factorial experimental design was used. The factors under investigation include extraction time, sample mass and acid concentration. Under optimized conditions, limits of detection (LOD) and limits of quantification (LOQ) ranged from 0.009 to 0.1 and 0.03-0.3µgg -1 , respectively. The repeatability (n=20) estimated in terms of relative standard deviation (%RSD) ranged from 0.9% to 3.7%. The accuracy of the proposed method was carried out using SRM 2709a. The obtained and certified/ indicative values were statistically in good agreement at 95% confidence level. The proposed method applied for quantification of As, Cr, Mo, Sb, Se and V in real soil samples. For comparison, the analytes of interest were also determined using a conventional acid digestion method. According to the paired t-test, the analytical results were not significant differences at 95% confidence level. The method was found to be accurate, precise and environmentally friendly. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Lower Choline-Containing Metabolites/Creatine (Cr) Rise and Failure to Sustain NAA/Cr Levels in the Dorsolateral Prefrontal Cortex Are Associated with Depressive Episode Recurrence under Maintenance Therapy: A Proton Magnetic Resonance Spectroscopy Retrospective Cohort Study.

    Science.gov (United States)

    Henigsberg, Neven; Šarac, Helena; Radoš, Marko; Radoš, Milan; Ozretić, David; Foro, Tamara; Erdeljić Turk, Viktorija; Hrabač, Pero; Bajs Janović, Maja; Rak, Benedict; Kalember, Petra

    2017-01-01

    The aim of this study was to evaluate the relationship between changes in proton magnetic resonance spectroscopy (1H-MRS) parameters at the start of the index episode recovery phase and at recurrence in patients with recurrent depression who were treated with prolonged maintenance therapy. 1H-MRS parameters were analyzed in 48 patients with recurrent depression who required maintenance therapy with antidepressant medication prescribed by a psychiatrist and who continued with the same antidepressant during the maintenance phase, either to recurrence of depression, completion of the 10-year observation period, or the start of the withdrawal phase (tapering-off antidepressant). N-acetylaspartate (NAA), choline-containing metabolites (Cho), creatine (Cr), and glutamine/glutamate were measured at the start of the recovery phase and 6 months later. Recurrent depressive episodes occurred in 20 patients. These individuals had a smaller increase in Cho/Cr after the beginning of the recovery phase compared to the non-recurrent patient group and also exhibited a decreased NAA/Cr ratio. Sustainable NAA and increased Cho levels at the onset of the recovery phase of the index episode are early markers of antidepressant effectiveness associated with a lower risk of major depressive disorder recurrence. The NAA and Cho changes in the non-recurrent group may be attributable to increased brain resilience, contrary to the transient temporal effect observed in subjects who experienced a depressive episode.

  18. Methionine and Choline Supply during the Periparturient Period Alter Plasma Amino Acid and One-Carbon Metabolism Profiles to Various Extents: Potential Role in Hepatic Metabolism and Antioxidant Status

    Directory of Open Access Journals (Sweden)

    Zheng Zhou

    2016-12-01

    Full Text Available The objective of this study was to profile plasma amino acids (AA and derivatives of their metabolism during the periparturient period in response to supplemental rumen-protected methionine (MET or rumen-protected choline (CHOL. Forty cows were fed from −21 through 30 days around parturition in a 2 × 2 factorial design a diet containing MET or CHOL. MET supply led to greater circulating methionine and proportion of methionine in the essential AA pool, total AA, and total sulfur-containing compounds. Lysine in total AA also was greater in these cows, indicating a better overall AA profile. Sulfur-containing compounds (cystathionine, cystine, homocystine, and taurine were greater in MET-fed cows, indicating an enriched sulfur-containing compound pool due to enhanced transsulfuration activity. Circulating essential AA and total AA concentrations were greater in cows supplied MET due to greater lysine, arginine, tryptophan, threonine, proline, asparagine, alanine, and citrulline. In contrast, CHOL supply had no effect on essential AA or total AA, and only tryptophan and cystine were greater. Plasma 3-methylhistidine concentration was lower in response to CHOL supply, suggesting less tissue protein mobilization in these cows. Overall, the data revealed that enhanced periparturient supply of MET has positive effects on plasma AA profiles and overall antioxidant status.

  19. Enhancing hepatic fibrosis in spontaneously hypertensive rats fed a choline-deficient diet: a follow-up report on long-term effects of oxidative stress in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Yamamoto, Hiroya; Kanno, Keishi; Ikuta, Takuya; Arihiro, Koji; Sugiyama, Akiko; Kishikawa, Nobusuke; Tazuma, Susumu

    2016-05-01

    We previously reported a model of non-alcoholic fatty liver disease (NAFLD) using spontaneously hypertensive rats (SHRs), fed a choline-deficient (CD) diet for 5 weeks, that hepatic steatosis but not fibrosis is developed through oxidative stress. To determine the relationship between hypertension and hepatic fibrosis in NAFLD, we examined whether long-term CD diet leads to hepatic fibrosis through oxidative stress. Eight-week-old male SHR and normotensive Wistar Kyoto rats (WKYs) were fed a CD diet for 5 or 20 weeks, then liver histology and hepatic expression of genes related to lipid metabolism, fibrosis, and oxidative stress were assessed. Oxidative stress was assessed by hepatic thiobarbituric acid reactive substance (TBARS) levels. After 5 weeks on CD diet, prominent hepatic steatosis and decrease in expression of genes for lipid metabolism were observed in SHRs as compared with WKYs. SHRs on a CD diet demonstrated a downregulated expression of genes for antioxidants, along with significant increases in hepatic TBARS. After 20 weeks on CD diet, SHRs demonstrated severe liver fibrosis and upregulated expressions of genes for fibrosis when compared with WKY. Hypertension precipitated hepatic steatosis, and further, acts as an enhancer in NAFLD progression to liver fibrosis through oxidative stress. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  20. Influence of a combination of two tetrachlorobiphenyl congeners (PCB 47; PCB 77) on thyroid status, choline acetyltransferase (ChAT) activity, and short- and long-term memory in 30-day-old Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Donahue, Douglas A.; Dougherty, Edward J.; Meserve, Lee A.

    2004-01-01

    The important role of thyroid hormones in growth and development, maintenance of body temperature, digestion, cardiac function, and normal brain development can be disrupted by environmental contaminants like polychlorinated biphenyls (PCB). Polychlorinated biphenyls are environmental contaminants that are widespread, persistent, lipophilic, and bioaccumulate through food webs, concentrating in adipose tissue. Placental and lactational PCB exposure of offspring causes metabolic and endocrine disruptions including hypothyroxinemia, spatial learning and memory deficits, neurochemical and neurobehavioral alterations, and reproductive problems. Previous studies in our lab using the individual congeners PCB 47 (2,2',4,4'-tetrachlorobiphenyl, ortho-substituted) and PCB 77 (3,3',4,4'-tetrachlorobiphenyl, non-ortho-substituted) have demonstrated alterations in thyroid hormone levels, alterations in brain choline acetyltransferase (ChAT) activity, and spatial learning deficits. In the present study, pregnant Sprague-Dawley rats were fed a diet with or without a mixture of PCB 47/77 at 1.25 ppm, 12.5 ppm or 25.0 ppm (w/w). Rat pups were swum in the Morris water maze four times a day on days 21-29 in order for the animals to learn the position of a submerged fixed platform. A probe test was run on day 24 (30 min after last swim) for short-term memory, and on day 29 (24 h after the last swim) for long-term memory after removal of the platform. Time spent in the quadrant previously containing the platform was recorded. Rats were decapitated on day 30, serum collected and frozen at -20 deg. ChAT activity was measured radiometrically in basal forebrain and hippocampus. All PCB-treated animals experienced a depression in both triiodothyronine (T 3 ) and thyroxine (T 4 ). The present study found that all doses of PCB depressed ChAT activity in hippocampus with no significant alteration in the basal forebrain. In PCB-treated animals, short-term memory showed a trend toward

  1. Gastrin-releasing peptide receptor-based targeting using bombesin analogues is superior to metabolism-based targeting using choline for in vivo imaging of human prostate cancer xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Rogier P.J. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus MC, Department of Urology, Rotterdam (Netherlands); Weerden, W.M. van; Bangma, C.H