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Sample records for choline reverses lead-induced

  1. Choline acetyltransferase: further studies on the reverse reaction

    International Nuclear Information System (INIS)

    Hsu, L.L.; Chao, L.P.

    1982-01-01

    In order to further characterize the reaction mechanism of brain ChAc in its purified form, we have investigated the reverse reaction of ChAc in terms of pH optimum, salt effects, and substrate kinetics using a radiochemical assay. We directly measured the reaction product acetylcoenzyme A which was separated from the substrate ACh by a cation exchange column. Dowex 50W-X8 (Na+ form). The reverse reaction of ChAc was linear with incubation time up to 40 minutes, and with enzyme protein concentration up to 5 micrograms. It had a pH optimum at 7.0. At 0.22 M the monovalent chloride and bromide salts activated the reverse ChAc activity by 23-47% but the fluoride and iodide salts inhibited the reverse enzyme activity by 10-30%. Kinetic studies in the absence of salt showed that KACh was 0.62 +/- 0.06 mM, KCoA . SH was 12.68 +/- 1.21 microM, and Vmax was 11.6 +/- 1.0 nmol AcCoA/mg protein/min. These data are in disagreement with the values reported on partially purified ChAc from bovine brain by Glover and Potter [1971] and Hersh [1980]. This indicates that further investigations are necessary to clarify or resolve these differences

  2. A Reversible, Charge-Induced Intramolecular C4a-S-Cysteinyl-Flavin in Choline Oxidase Variant S101C.

    Science.gov (United States)

    Su, Dan; Yuan, Hongling; Gadda, Giovanni

    2017-12-26

    Choline oxidase serves as a paradigm for alcohol oxidation catalyzed by flavin-dependent enzymes. In its active site, S101 is 4 Å from the flavin C4a atom on an extended loop. Enzyme variants substituted at S101 were generated in a previous study and investigated mechanistically [Yuan, H., and Gadda, G. (2011) Biochemistry 50, 770-779]. In this study, the typical ultraviolet-visible (UV-vis) absorption spectrum of oxidized flavin was observed for the S101C enzyme in HEPES, TES, or sodium phosphate, whereas an absorption spectrum suggesting the presence of a C4a-flavin adduct with cysteine was obtained in Tris-HCl at pH 8.0. pH titrations of the UV-vis absorption spectrum of the wild-type, S101A, S101C, and H99N enzymes in the presence and absence of Tris allowed for the determination of two pK a values that define a pH range in which the C4a-S-cysteinyl flavin is stabilized. Inhibition studies and stopped-flow kinetics demonstrated that binding of protonated Tris in the active site of the S101C enzyme is required to form the C4a-S-cysteinyl flavin. Deuterium kinetic isotope effects and proton inventories of the S101C enzyme mixed in a stopped-flow spectrophotometer with Tris established a mechanism for the reversible formation of the C4a-S-cysteinyl flavin. This study provides a detailed mechanistic analysis of the reversible formation of a bicovalent C4a-S-cysteinyl-8α-N 3 -histidyl flavin in choline oxidase, identifying an optimal pH range and a mechanistic rationale for the stabilization of de novo C4a-S-cysteinyl-flavins. Moreover, it presents an example of an intramolecular reaction of an enzyme-bound flavin without a substrate.

  3. Choline reverses scopolamine-induced memory impairment by improving memory reconsolidation.

    Science.gov (United States)

    Blake, M G; Boccia, M M; Krawczyk, M C; Delorenzi, A; Baratti, C M

    2012-09-01

    It is widely known that pre-training systemic administration of the muscarinic antagonist scopolamine (SCP) (0.5mg/kg, i.p.) leads to anterograde memory impairment in retention tests. The administration of the α(7)-nicotinic receptor agonist choline (Ch) in the dorsal hippocampus (0.8μg/hippocampus) immediately after memory reactivation allowed recovery from scopolamine-induced memory impairment. This effect of Ch was time-dependent, and retention performance was not affected in drug-treated mice that were not subjected to memory reactivation, suggesting that the performance effects are not due to non-specific effects of the drug. The effects of Ch also depended on the age of the reactivated memory. Altogether, our results suggest that Ch exerts its effects by modulating memory reconsolidation, and that the memory impairment induced by low doses of SCP is a memory expression failure and not a storage deficit. Therefore, reconsolidation, among other functions, might serve to change memory expression in later tests. Summarizing, our results open new avenues about the behavioral significance and the physiological functions of memory reconsolidation, providing new strategies for recovering memories from some types of amnesia. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. 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- ...

  5. 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...

  6. 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.

  7. 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......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...

  8. 21 CFR 182.8252 - Choline chloride.

    Science.gov (United States)

    2010-04-01

    ... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8252 Choline chloride. (a) Product. Choline chloride. (b) Conditions of use. This substance is generally recognized as...

  9. 21 CFR 182.8250 - Choline bitartrate.

    Science.gov (United States)

    2010-04-01

    ... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8250 Choline bitartrate. (a) Product. Choline bitartrate. (b) Conditions of use. This substance is generally recognized as...

  10. 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.

  11. 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.

  12. 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.

  13. Glioprotective Effects of Ashwagandha Leaf Extract against Lead Induced Toxicity

    Directory of Open Access Journals (Sweden)

    Praveen Kumar

    2014-01-01

    Full Text Available Withania somnifera (Ashwagandha, also known as Indian Ginseng, is a well-known Indian medicinal plant due to its antioxidative, antistress, antigenotoxic, and immunomodulatory properties. The present study was designed to assess and establish the cytoprotective potential of Ashwagandha leaf aqueous extract against lead induced toxicity. Pretreatment of C6 cells with 0.1% Ashwagandha extract showed cytoprotection against 25 μM to 400 μM concentration of lead nitrate. Further pretreatment with Ashwagandha extract to lead nitrate exposed cells (200 μM resulted in normalization of glial fibrillary acidic protein (GFAP expression as well as heat shock protein (HSP70, mortalin, and neural cell adhesion molecule (NCAM expression. Further, the cytoprotective efficacy of Ashwagandha extract was studied in vivo. Administration of Ashwagandha extract provided significant protection to lead induced altered antioxidant defense that may significantly compromise normal cellular function. Ashwagandha also provided a significant protection to lipid peroxidation (LPx levels, catalase, and superoxide dismutase (SOD but not reduced glutathione (GSH contents in brain tissue as well as peripheral organs, liver and kidney, suggesting its ability to act as a free radical scavenger protecting cells against toxic insult. These results, thus, suggest that Ashwagandha water extract may have the potential therapeutic implication against lead poisoning.

  14. Lead induced oxidative stress: beneficial effects of Kombucha tea.

    Science.gov (United States)

    Dipti, P; Yogesh, B; Kain, A K; Pauline, T; Anju, B; Sairam, M; Singh, B; Mongia, S S; Kumar, G Ilavazhagan Devendra; Selvamurthy, W

    2003-09-01

    To evaluate the effect of oral administration of Kombucha tea (K-tea) on lead induced oxidative stress. Sprague Dawley rats were administered 1 mL of 3.8% lead acetate solution daily alone or in combination with K-tea orally for 45 d, and the antioxidant status and lipid peroxidation were evaluated. Oral administration of lead acetate to rats enhanced lipid peroxidation and release of creatine phosphokinase and decreased levels of reduced glutathione (GSH) and antioxidant enzymes (superoxide dismutase, SOD and glutathione peroxidase, GPx). Lead treatment did not alter humoral immunity, but inhibited DTH response when compared to the control. Lead administration also increased DNA fragmentation in liver. Oral administration of Kombucha tea to rats exposed to lead decreased lipid peroxidation and DNA damage with a concomitant increase in the reduced glutathione level and GPx activity. Kombucha tea supplementation relieved the lead induced immunosuppression to appreciable levels. The results suggest that K-tea has potent antioxidant and immunomodulating properties.

  15. 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

  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-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.)

  18. Pre- and postnatal health: evidence of increased choline needs.

    Science.gov (United States)

    Caudill, Marie A

    2010-08-01

    Choline, a micronutrient found in food, serves as the starting material for several important metabolites that play key roles in fetal development, particularly the brain. Although human beings' requirement for choline is unknown, an Adequate Intake level of 425 mg/day was established for women with upward adjustments to 450 and 550 mg/day during pregnancy and lactation, respectively. The importance of choline in human development is supported by observations that a human fetus receives a large supply of choline during gestation; pregnancy causes depletion of hepatic choline pools in rats consuming a normal diet; human neonates are born with blood levels that are three times higher than maternal blood concentrations; and large amounts of choline are present in human milk. The development of the central nervous system is particularly sensitive to choline availability with evidence of effects on neural tube closure and cognition. Existing data show that the majority of pregnant (and presumably lactating) women are not achieving the target intake levels and that certain common genetic variants may increase requirements for choline beyond current recommendations. Because choline is not found in most varieties of prenatal vitamins (or regular multivitamins), increased consumption of choline-rich foods may be needed to meet the high pre- and postnatal demands for choline. 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

  19. 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.

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

    Science.gov (United States)

    Waddell, Jaylyn; Mooney, Sandra M

    2017-09-29

    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.

  1. Exercise and neuromodulators: choline and acetylcholine in marathon runners

    Science.gov (United States)

    Conlay, L. A.; Sabounjian, L. A.; Wurtman, R. J.

    1992-01-01

    Certain neurotransmitters (i.e., acetylcholine, catecholamines, and serotonin) are formed from dietary constituents (i.e., choline, tyrosine and tryptophan). Changing the consumption of these precursors alters release of their respective neurotransmitter products. The neurotransmitter acetylcholine is released from the neuromuscular junction and from brain. It is formed from choline, a common constituent in fish, liver, and eggs. Choline is also incorporated into cell membranes; membranes may likewise serve as an alternative choline source for acetylcholine synthesis. In trained athletes, running a 26 km marathon reduced plasma choline by approximately 40%, from 14.1 to 8.4 uM. Changes of similar magnitude have been shown to reduce acetylcholine release from the neuromuscular junction in vivo. Thus, the reductions in plasma choline associated with strenuous exercise may reduce acetylcholine release, and could thereby affect endurance or performance.

  2. 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.

  3. 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.

  4. Absolute Quantification of Choline-Related Biomarkers in Breast Cancer Biopsies by Liquid Chromatography Electrospray Ionization Mass Spectrometry

    Science.gov (United States)

    Mimmi, Maria Chiara; Finato, Nicoletta; Pizzolato, Gloria; Beltrami, Carlo Alberto; Fogolari, Federico; Corazza, Alessandra; Esposito, Gennaro

    2013-01-01

    It has been repeatedly demonstrated that choline metabolism is altered in a wide variety of cancers. In breast tumours, the choline metabolite profile is characterized by an elevation of phosphocholine and total choline-compounds. This pattern is increasingly being exploited as biomarker in cancer diagnosis. The majority of in vitro metabolomics studies, for biomarkers quantification in cell cultures or tissues, entail proton NMR spectroscopy. Although many “targeted” approaches have been proposed to quantify metabolites from standard one-dimensional (1D) NMR experiments, the task is often made difficult by the high degree of overlap characterizing 1H NMR spectra of biological samples. Here we present an optimized protocol for tissue extraction and absolute quantification of choline, phosphocholine and glycerophosphocholine by means of liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). The selected chromatographic separation system with a HILIC (hydrophilic interaction chromatography) amide column effectively separates free choline and its phopshorylated derivatives, contrary to failure observed using standard reversed-phase chromatography. The metabolite absolute quantification is based on external calibration with commercial standards, and is validated by a parallel 1D proton NMR analysis. The LC-MS/NMR analysis is applied to three breast carcinoma specimens obtained by surgical excision, each one accompanied by a control tissue sample taken outside the tumor margin. The metabolite concentrations measured are in good agreement with previous results on metabolic profile changes of breast cancer. Each of the three cancerous biopsies, when compared with the control tissue, exhibit a highly increased levels phosphocholine, total choline and phosphocholine/glycerophosphocholine ratio. PMID:24036926

  5. A Review on Electrochemical Properties of Choline Chloride Based ...

    African Journals Online (AJOL)

    ADOWIE PERE

    quaternary ammonium halide and a hydrogen bond donor such as alcohol have advantage for metal extraction and ... organic salts, amino acids, or choline derivatives. (Dai, 2013). It's evident that these DESs fully fulfil ... such as choline chloride, urea, and organic acids, have been reported especially considering their low.

  6. Uptake and kinetic properties of choline and ethanolamine in ...

    African Journals Online (AJOL)

    Poracom

    to investigate the respective shape of the uptake of choline and ethanolamine by Plasmodium falciparum. Method: ..... composition in the erythrocyte membrane and ... 7. Fossati T, Colombo M, Castiglioni C, Abbiati G. Determination of plasma choline by high- performance liquid chromatography with a postcolumn enzyme.

  7. Choline associated hypersexuality in a 79-year-old man.

    Science.gov (United States)

    Calabrò, Rocco Salvatore; Cordici, Francesco; Genovese, Carmelo; Bramanti, Placido

    2014-01-01

    Hypersexuality, also referred to as sexually inappropriate behavior and sexual disinhibition, involves persistent, uninhibited sexual behaviors directed at oneself or at others, sometimes associated with neurodegenerative disorders. Choline is a water-soluble essential nutrient, used as a dietary supplement in different diseases. This report was aimed at considering choline intake as a possible cause of iatrogenic hypersexuality. After an evaluation, a 79-year-old man affected by memory loss was diagnosed with mild cognitive impairment and treated with oral choline. After 6 weeks of regular choline assumption, the patient showed a pathological increase in libido with sexual urges. As choline was withdrawn, the hypersexuality disappeared within 5 days. Since hypersexuality may be an underreported and overlooked adverse effect of drugs and dietary supplements acting on the cholinergic pathway, this should be considered when treating and counselling patients with inappropriate sexual behavior.

  8. GRIN2A polymorphisms and expression levels are associated with lead-induced neurotoxicity.

    Science.gov (United States)

    Wu, Yu; Wang, Yiqing; Wang, Miaomiao; Sun, Na; Li, Chunping

    2017-04-01

    Lead acts as an antagonist of the N-methyl-d-aspartate receptor (NMDAR). GRIN2A encodes an important subunit of NMDARs and may be a critical factor in the mechanism of lead neurotoxicity. Changes in GRIN2A expression levels or gene variants may be mechanisms of lead-induced neurotoxicity. In this study, we hypothesized that GRIN2A might contribute to lead-induced neurotoxicity. A preliminary HEK293 cell experiment was performed to analyze the association between GRIN2A expression and lead exposure. In addition, in a population-based study, serum GRIN2A levels were measured in both lead-exposed and control populations. To detect further the influence of GRIN2A gene single nucleotide polymorphisms (SNPs) in lead-induced neurotoxicity, 3 tag SNPs (rs2650429, rs6497540, and rs9302415) were genotyped in a case-control study that included 399 lead-exposed subjects and 398 controls. Lead exposure decreased GRIN2A expression levels in HEK293 cells ( p lead-free cells. Lead-exposed individuals had lower serum GRIN2A levels compared with controls ( p lead level ( p lead poisoning compared with the rs2650429 CC genotype (adjusted odds ratio = 1.42, 95% confidence interval = 1.01-2.00]. Therefore, changes in GRIN2A expression levels and variants may be important mechanisms in the development of lead-induced neurotoxicity.

  9. 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

  10. 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

  11. Mechanisms of acetylcholine synthesis: Coupling with choline transport

    International Nuclear Information System (INIS)

    Rylett, R.J.

    1986-01-01

    Comparative studies were performed to assess the utilization of choline transported by synaptosomal sodium-dependent, high-affinity choline carriers for the synthesis of ACh; it was determined that a significantly higher percentage of tritium-choline transported into rat forebrain synaptosomes was acetylated immediately compared to that of guinea-pig. Studies were performed to determine whether inhibition of synaptosomal ChAT was produced by incubating guinea-pig brain synaptosomes with ChMAz, comparable to that observed with rat brain synaptosomes. Very little ChAT activity was measured in guinea-pig brain; that this difference could reflect differing subcellular localizations of ChAT and different relativities with respect to coupling with choline carriers is speculative and currtly being investigated

  12. Choline nutrition programs brain development via DNA and histone methylation.

    Science.gov (United States)

    Blusztajn, Jan Krzysztof; Mellott, Tiffany J

    2012-06-01

    Choline is an essential nutrient for humans. Metabolically choline is used for the synthesis of membrane phospholipids (e.g. phosphatidylcholine), as a precursor of the neurotransmitter acetylcholine, and, following oxidation to betaine, choline functions as a methyl group donor in a pathway that produces S-adenosylmethionine. As a methyl donor choline influences DNA and histone methylation--two central epigenomic processes that regulate gene expression. Because the fetus and neonate have high demands for choline, its dietary intake during pregnancy and lactation is particularly important for normal development of the offspring. Studies in rodents have shown that high choline intake during gestation improves cognitive function in adulthood and prevents memory decline associated with old age. These behavioral changes are accompanied by electrophysiological, neuroanatomical, and neurochemical changes and by altered patterns of expression of multiple cortical and hippocampal genes including those encoding key proteins that contribute to the biochemical mechanisms of learning and memory. These actions of choline are observed long after the exposure to the nutrient ended (months) and correlate with fetal hepatic and cerebral cortical choline-evoked changes in global- and gene-specific DNA cytosine methylation and with dramatic changes of the methylation pattern of lysine residues 4, 9 and 27 of histone H3. Moreover, gestational choline modulates the expression of DNA (Dnmt1, Dnmt3a) and histone (G9a/Ehmt2/Kmt1c, Suv39h1/Kmt1a) methyltransferases. In addition to the central role of DNA and histone methylation in brain development, these processes are highly dynamic in adult brain, modulate the expression of genes critical for synaptic plasticity, and are involved in mechanisms of learning and memory. A recent study documented that in a cohort of normal elderly people, verbal and visual memory function correlated positively with the amount of dietary choline consumption

  13. Characterization of choline transporters in the human placenta over gestation.

    Science.gov (United States)

    Baumgartner, Heidi K; Trinder, Kinsey M; Galimanis, Carly E; Post, Annalisa; Phang, Tzu; Ross, Randal G; Winn, Virginia D

    2015-12-01

    The developing fetus relies on the maternal blood supply to provide the choline it requires for making membrane lipids, synthesizing acetylcholine, and performing important methylation reactions. It is vital, therefore, that the placenta is efficient at transporting choline from the maternal to the fetal circulation. Although choline transporters have been found in term placenta samples, little is known about what cell types express specific choline transporters and how expression of the transporters may change over gestation. The objective of this study was to characterize choline transporter expression levels and localization in the human placenta throughout placental development. We analyzed CTL1 and -2 expression over gestation in human placental biopsies from 6 to 40 weeks gestation (n = 6-10 per gestational window) by immunoblot analysis. To determine the cellular expression pattern of the choline transporters throughout gestation, immunofluorescence analysis was then performed. Both CTL1 and CTL2 were expressed in the chorionic villi from 6 weeks gestation to term. Labor did not alter expression levels of either transporter. CTL1 localized to the syncytial trophoblasts and the endothelium of the fetal vasculature within the chorionic villous structure. CTL2 localized mainly to the stroma early in gestation and by the second trimester co-localized with CTL1 at the fetal vasculature. The differential expression pattern of CTL1 and CTL2 suggests that CTL1 is the key transporter involved in choline transport from maternal circulation and both transporters are likely involved in stromal and endothelial cell choline transport. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Parallel Colorimetric Quantification of Choline and Phosphocholine as a Method for Studying Choline Kinase Activity in Complex Mixtures

    Directory of Open Access Journals (Sweden)

    Tahl Zimmerman

    2018-03-01

    Full Text Available Choline kinase (Chok is an enzyme found in eukaryotes and Gram-positive bacteria. Chok catalyzes the production of phosphocholine from choline and ATP. This enzyme has been validated as a drug target in Streptococcus pneumonia, but the role Chok enzymatic activity plays in bacterial cell growth and division is not well understood. Phosphocholine production by Chok and its attenuation by inhibitors in the context of complex samples such as cell extracts can currently be quantified by several methods. These include choline depletion measurements, radioactive methods, mass-spectrometry, and nuclear magnetic resonance. The first does not measure phosphocholine directly, the second requires elaborate safety procedures, and the third and fourth require significant capital investments and technical expertise. For these reasons, a less expensive, higher throughput, more easily accessible assay is needed to facilitate further study in Gram-positive Choks. Here, we present the development of a triiodide/activated charcoal/molybdenum blue system for detecting and quantifying choline and phosphocholine in parallel. We demonstrate that this system can reliably quantify changes in choline and phosphocholine concentrations over time in Chok enzymatic assays using cell extracts as the source of the enzyme. This is an easily accessible, convenient, robust, and economical method for studying Chok activity in complex samples. The triiodide/activated charcoal/molybdenum blue system opens new doors into the study choline kinase in Gram-positive pathogens.

  15. Synthesis, isolation and purification of [11C]-choline

    Directory of Open Access Journals (Sweden)

    Marcin Szydło

    2016-08-01

    Full Text Available [11C]-choline is an effective PET tracer used for imaging of neoplastic lesions and metastases of the prostate cancer. However, its production can be a challenge for manufacturers, as it has not yet been described in Polish or European pharmacopoeia. In this study the technical aspects of [11C]-choline production are described and detailed process parameters are provided. The quality control procedures for releasing [11C]-choline as solutio iniectabilis are also presented. The purity and quality of the radiopharmaceutical obtained according to the proposed method were find to be high enough to safely administrate the radiopharmaceutical to patients. Application of an automated synthesizer makes it possible to carry out the entire process of [11C]-choline production, isolation and purification within 20 minutes. It is crucial to maintain all aspects of the process as short as possible, since the decay half-time of carbon-11 is 20.4 minutes. The resulting radiopharmaceutical is sterile and pyrogen-free and of a high chemical, radiochemical, and radionuclide purity proved by chromatographic techniques. The yield of the process is up to 20%. [11C]-choline PET scanning can be used as accurate and effective diagnostic tool in all centers equipped with [11C]-target containing cyclotron.

  16. 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)

  17. 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

  18. Ethanolamine and Choline Promote Expression of Putative and Characterized Fimbriae in Enterohemorrhagic Escherichia coli O157:H7

    Science.gov (United States)

    Gonyar, Laura A.

    2014-01-01

    Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important food-borne pathogen responsible for disease outbreaks worldwide. In order to colonize the human gastrointestinal (GI) tract and cause disease, EHEC must be able to sense the host environment and promote expression of virulence genes essential for adherence. Ethanolamine (EA) is an important metabolite for EHEC in the GI tract, and EA is also a signal that EHEC uses to activate virulence traits. Here, we report that EA influenced EHEC adherence to epithelial cells and fimbrial gene expression. Quantitative reverse transcriptase PCR indicated that EA promoted the transcription of the genes in characterized and putative fimbrial operons. Moreover, putative fimbrial structures were produced by EHEC cells grown with EA but not in medium lacking EA. Additionally, we defined two previously uncharacterized EA-regulated fimbrial operons, loc10 and loc11. We also tested whether choline or serine, both of which are also components of cell membranes, activated fimbrial gene expression. In addition to EA, choline activated fimbrial gene expression in EHEC. These findings describe for the first time the transcription of several putative fimbrial loci in EHEC. Importantly, the biologically relevant molecules EA and choline, which are abundant in the GI tract, promoted expression of these fimbriae. PMID:24126525

  19. The association of serum choline with linear growth failure in young children from rural Malawi.

    Science.gov (United States)

    Semba, Richard D; Zhang, Pingbo; Gonzalez-Freire, Marta; Moaddel, Ruin; Trehan, Indi; Maleta, Kenneth M; Ordiz, M Isabel; Ferrucci, Luigi; Manary, Mark J

    2016-07-01

    Choline is an essential nutrient for cell structure, cell signaling, neurotransmission, lipid transport, and bone formation. Choline can be irreversibly converted to betaine, a major source of methyl groups. Trimethylene N-oxide (TMAO), a proatherogenic molecule, is produced from the metabolism of dietary choline by the gut microbiome. The relation between serum choline and its closely related metabolites with linear growth in children is unknown. The aim was to characterize the relation between serum choline and its closely related metabolites, betaine and TMAO, with linear growth and stunting in young children. We measured serum choline, betaine, and TMAO concentrations by using liquid chromatography isotopic dilution tandem mass spectrometry in a cross-sectional study in 325 Malawian children, aged 12-59 mo, of whom 62% were stunted. Median (25th, 75th percentile) serum choline, betaine, and TMAO concentrations were 6.4 (4.8, 8.3), 12.4 (9.1, 16.3), and 1.2 (0.7, 1.8) μmol/L, respectively. Spearman correlation coefficients of age with serum choline, betaine, and TMAO were -0.57 (P Children with and without stunting had median (25th, 75th percentile) serum choline concentrations of 5.6 (4.4, 7.4) and 7.3 (5.9, 9.1) μmol/L (P growth failure in young children is associated with low serum choline and elevated betaine-to-choline and TMAO-to-choline ratios. Further work is needed to understand whether low dietary choline intake explains low circulating choline among stunted children living in low-income countries and whether increasing choline intake may correct choline deficiency and improve growth and development. This trial was registered in the ISRCTN registry (www.isrctn.com) as ISRCTN14597012. © 2016 American Society for Nutrition.

  20. Preventive efficacy of bulk and nanocurcumin against lead-induced oxidative stress in mice.

    Science.gov (United States)

    Flora, Gagan; Gupta, Deepesh; Tiwari, Archana

    2013-04-01

    Chronic lead exposure is associated with several health disorders in humans and animals. Lead exposure leads to the generation of reactive oxygen species and depletes body antioxidant enzymes causing damage to various macromolecules and ultimately cell death. Curcumin has been widely recognized to protect against metal toxicity but has major limitations of reduced bioavailability. Nanoencapsulation of curcumin could be an effective strategy to combat lead induced toxic manifestations. The present study investigates the protective efficacy of bulk and nanocurcumin against lead-induced toxicity. Swiss albino mice were daily exposed to lead acetate (25 mg/kg, i.p.) alone and after 1 h treated either with curcumin (15 mg/kg, orally) or nanocurcumin (15 mg/kg, orally) for two consecutive weeks. The preventive efficacy of nanocurcumin was evaluated against various altered biochemical variables suggestive of oxidative stress and lead accumulation in blood and soft tissues. Coadministration of nanocurcumin with lead restored the altered δ-aminolevulinic acid dehydratase activity, glutathione (reduced and oxidized) levels, and also decreased reactive oxygen species, and thiobarbituric acid reactive substances levels. Nanocurcumin due to its possible chelating property and enhanced bioavailability efficiently removed lead from blood and soft tissues compared to bulk curcumin. Results demonstrate the enhanced preventive efficacy of nanocurcumin and suggest an interesting and novel approach for better treatment of lead toxicity.

  1. 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

  2. Choline Derivatives Involved in Osmotolerance of Penicillium fellutanum†

    Science.gov (United States)

    Park, Yong-Il; Gander, John E.

    1998-01-01

    Penicillium fellutanum is osmotolerant and xerotolerant when cultured in a low-phosphate medium containing 3 M NaCl. Glycerol and erythritol accumulated in cultures with NaCl concentrations up to 2 M; glycerol was the only detectable polyol in cultures containing 3 M NaCl. In cultures with 3 M NaCl, the intracellular levels of glycine betaine and choline-O-sulfate were 22- and 2.6-fold greater (70 and 46 mM), respectively, than those of cultures without added NaCl. The levels of glycine betaine and glycerol decreased in mycelia transferred from a medium containing 3 M NaCl into a fresh medium without added NaCl. NaCl at 3 M inhibited mycelial mass accumulation; this inhibition was partially corrected by supplementation of cultures with glycine betaine (2 mM) or choline-O-sulfate (10 mM). The presence of exogenous choline chloride (2 mM) in plate cultures protected the cells from stress from 3 M NaCl. The data suggest that glycine betaine and choline-O-sulfate are secondary osmoprotectants which are effective at the point that the cell is incapable of synthesizing more glycerol. PMID:16349488

  3. Lead-induced SCC of alloy 600 in plausible steam generator crevice environments

    Energy Technology Data Exchange (ETDEWEB)

    Wright, M.D. [Atomic Energy of Canada Limited, Chalk River, Ontario (Canada); Manolescu, A. [Ontario Hydro Technologies, Toronto, Ontario (Canada); Mirzai, M. [Ontario Hydro, Toronto, Ontario (Canada)

    1998-07-01

    Laboratory stress corrosion cracking (SCC) test environments developed to simulate representative BNGS-A steam generator (SG) crevice chemistries have been used to determine the susceptibility of Alloy 600 to lead-induced SCC under plausible SG conditions. Test environments were based on plant SG hideout return data and analysis of removed tubes and deposits. Deviations from the normal near neutral crevice pH environment were considered to simulate possible faulted excursion crevice chemistry and to bound the postulated crevice pH range of 3-9 (at temperature). The effect of lead contamination up to 1000 ppm, but with an emphasis on the 100 to 500 ppm range, was determined. SCC susceptibility was investigated using constant extension rate tensile (CERT) tests and encapsulated C-ring tests. CERT tests were performed at 305 degrees C on tubing representative of BNGS-A SG U-bends. The C-ring test method allowed a wider test matrix covering three temperatures (280, 304 and 315 degrees C), three strain levels (0.2%, 2% and 4%) and tubing representative of U-bends plus tubing given a simulated stress relief to represent material at the tubesheet. The results of this test program confirmed that in the absence of lead contamination, cracking does not occur in these concentrated, 3.3 to 8.9 pH range, crevice environments. Also, it appears that the concentrated crevice environments suppress lead-induced cracking relative to that seen in all-volatile-treatment (AVT) water. For the (static) C-ring tests, lead-induced SCC was only produced in the near-neutral crevice environment and was more severe at 500 ppm than 100 ppm PbO. This trend was also observed in CERT tests but some cracking/grain boundary attack occurred in acidic (pH 3.3) and alkaline (pH 8.9) environments. The C-ring tests indicated that a certain amount of resistance to cracking was imparted by simulated stress relief of the tubing. This heat treatment, confirmed to have resulted in sensitization, promoted

  4. Lead-induced stress-corrosion cracking of alloy 600 in plausible steam generator crevice environments

    Energy Technology Data Exchange (ETDEWEB)

    Wright, M.D. [Atomic Energy of Canada Limited, Chalk River, Ontario (Canada); Manolescu, A. [Ontario Hydro Technologies, Toronto, Ontario (Canada); Mirzai, M. [Ontario Hydro, Toronto, Ontario (Canada)

    1999-03-01

    Laboratory stress-corrosion cracking (SCC) test environments were developed to simulate crevice chemistries representative of Bruce Nuclear Generating Station A (BNPD A) steam generators (SGs); these test environments were used to determine the susceptibility of Alloy 600 to lead-induced SCC under plausible SG conditions. Test environments were based on plant SG hideout return data and analysis of removed tubes and deposits. Deviations from the normal near-neutral crevice pH environment were considered to simulate possible faulted excursion crevice chemistry and to bound the postulated crevice pH range of 3 to 9 (at temperature). The effect of lead contamination up to 1000 ppm, but with an emphasis on the 100- to 500-ppm range, was determined. SCC susceptibility was investigated using constant extension rate tensile (CERT) tests and encapsulated C-ring tests. CERT tests were performed at 305 degrees C on tubing representative of BNPD A SG U-bends. The C-ring test method allowed a wider test matrix, covering 3 temperatures (280 degrees C, 304 degrees C and 315 degrees C), 3 strain levels (0.2%, 2% and 4%), and tubing representative of U-bends plus tubing given a simulated stress relief to represent material at the tube sheet. The results of this test program confirmed that in the absence of lead contamination, cracking does not occur in these concentrated, 3.3 to 8.9 pH range, crevice environments. Also, it appears that the concentrated crevice environments suppress lead-induced cracking relative to that seen in all-volatile-treatment (AVT) water. For the (static) C-ring tests, lead-induced SCC was only produced in the near-neutral crevice environment and was more severe at 500 ppm than at 100 ppm PbO. This trend was also observed in CERT tests, but some cracking-grain boundary attack occurred in acidic (pH 3.3) and alkaline (pH 8.9) environments. The C-ring tests indicated that a certain amount of resistance to cracking was imparted by simulated stress relief of

  5. 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.

  6. 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.

  7. Characterization of kidney sulfotransferases during lead-induced nephrotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Templer, L.A.; Kong, J.; Ronis, M.J.J.; Ringer, D.P. [Univ. Arkansas Medical School, Little Rock, AR (United States)

    1996-03-08

    Kidney sulfotransferases (ST) have been shown to be involved in the biotransformation of steroid and thyroid hormones as well as xenobiotics varying from carcinogenic heterocyclic amines to drugs such as acetaminophen. In order to examine the impact of lead-induced nephrotoxicity on kidney aryl, estrogen and DHEA STs during growth and development, time-impregnated female Sprague-Dawley rats were exposed ad libitum to lead acetate (0.6%) in drinking water from gestational day 5 and continuing in male and female pups until they were sacrificed at day 85. Cytosols from male rat kidneys showed levels of estrogen ST activity (59% of females) that were significantly lowered (P{le}0.05) after lead exposure (6-20% of male). Aryl ST activity was relatively unchanged in male rats after rat kidney cytosol. Immunochemical analysis of cytosols from normal males and females with the antiserums to the three STs substantiated the presence of only the aryl and estrogen STs. Immunohistochemical techniques localized the aryl and estrogen STs primarily to the S3 section of the proximal tubules. These findings indicate that kidney STs may be differently modulated during lead exposure.

  8. 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.

  9. Proanthocyanidins Attenuation of Chronic Lead-Induced Liver Oxidative Damage in Kunming Mice via the Nrf2/ARE Pathway

    Directory of Open Access Journals (Sweden)

    Miao Long

    2016-10-01

    Full Text Available Lead is harmful for human health and animals. Proanthocyanidins (PCs, a natural antioxidant, possess a broad spectrum of pharmacological and medicinal properties. However, its protective effects against lead-induced liver damage have not been clarified. This study was aimed to evaluate the protective effect of PCs on the hepatotoxicity of male Kunming mice induced by chronic lead exposure. A total of 70 healthy male Kunming mice were averagely divided into four groups: control group, i.e., the group exposed to lead, the group treated with PCs, and the group co-treated with lead and PCs. The mice exposed to lead were given water containing 0.2% lead acetate. Mice treated in the PCs and PCs lead co-treated groups were given PC (100 mg/kg in 0.9% saline by oral gavage. Lead exposure caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, and inhibition of antioxidant enzyme activities. The induction of oxidative stress and histological alterations in the liver were minimized by co-treatment with PCs. Meanwhile, the number of Transferase-Mediated Deoxyuridine Triphosphate-Biotin Nick End Labeling (TUNEL-positive cells was significantly reduced in the PCs/lead co-treated group compared to the lead group. In addition, the lead group showed an increase in the expression level of Bax, while the expression of Bcl-2 was decreased. Furthermore, the lead group showed an increase in the expression level of endoplasmic reticulum (ER stress-related genes and protein (GRP78 and CHOP. Co-treated with PCs significantly reversed these expressions in the liver. PCs were, therefore, demonstrated to have protective, antioxidant, and anti-ER stress and anti-apoptotic activities in liver damage caused by chronic lead exposure in the Kunming mouse. This may be due to the ability of PCs to enhance the ability of liver tissue to protect against oxidative stress via the Nrf2/ARE signaling pathway, resulting in decreasing ER stress

  10. Proanthocyanidins Attenuation of Chronic Lead-Induced Liver Oxidative Damage in Kunming Mice via the Nrf2/ARE Pathway.

    Science.gov (United States)

    Long, Miao; Liu, Yi; Cao, Yu; Wang, Nan; Dang, Meng; He, Jianbin

    2016-10-21

    Lead is harmful for human health and animals. Proanthocyanidins (PCs), a natural antioxidant, possess a broad spectrum of pharmacological and medicinal properties. However, its protective effects against lead-induced liver damage have not been clarified. This study was aimed to evaluate the protective effect of PCs on the hepatotoxicity of male Kunming mice induced by chronic lead exposure. A total of 70 healthy male Kunming mice were averagely divided into four groups: control group, i.e., the group exposed to lead, the group treated with PCs, and the group co-treated with lead and PCs. The mice exposed to lead were given water containing 0.2% lead acetate. Mice treated in the PCs and PCs lead co-treated groups were given PC (100 mg/kg) in 0.9% saline by oral gavage. Lead exposure caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, and inhibition of antioxidant enzyme activities. The induction of oxidative stress and histological alterations in the liver were minimized by co-treatment with PCs. Meanwhile, the number of Transferase-Mediated Deoxyuridine Triphosphate-Biotin Nick End Labeling (TUNEL)-positive cells was significantly reduced in the PCs/lead co-treated group compared to the lead group. In addition, the lead group showed an increase in the expression level of Bax, while the expression of Bcl-2 was decreased. Furthermore, the lead group showed an increase in the expression level of endoplasmic reticulum (ER) stress-related genes and protein (GRP78 and CHOP). Co-treated with PCs significantly reversed these expressions in the liver. PCs were, therefore, demonstrated to have protective, antioxidant, and anti-ER stress and anti-apoptotic activities in liver damage caused by chronic lead exposure in the Kunming mouse. This may be due to the ability of PCs to enhance the ability of liver tissue to protect against oxidative stress via the Nrf2/ARE signaling pathway, resulting in decreasing ER stress and apoptosis of

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

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    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

  12. Central injection of captopril inhibits the blood pressure response to intracerebroventricular choline

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    N. Isbil-Buyukcoskun

    2001-06-01

    Full Text Available In the present study, we investigated the involvement of the brain renin-angiotensin system in the effects of central cholinergic stimulation on blood pressure in conscious, freely moving normotensive rats. In the first step, we determined the effects of intracerebroventricular (icv choline (50, 100 and 150 µg on blood pressure. Choline increased blood pressure in a dose-dependent manner. In order to investigate the effects of brain renin-angiotensin system blockade on blood pressure increase induced by choline (150 µg, icv, an angiotensin-converting enzyme inhibitor, captopril (25 and 50 µg, icv, was administered 3 min before choline. Twenty-five µg captopril did not block the pressor effect of choline, while 50 µg captopril blocked it significantly. Our results suggest that the central renin-angiotensin system may participate in the increase in blood pressure induced by icv choline in normotensive rats.

  13. 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.

  14. 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

  15. Concentrations of Water-Soluble Forms of Choline in Human Milk from Lactating Women in Canada and Cambodia

    Directory of Open Access Journals (Sweden)

    Alejandra M. Wiedeman

    2018-03-01

    Full Text Available Choline has critical roles during periods of rapid growth and development, such as infancy. In human milk, choline is mostly present in water-soluble forms (free choline, phosphocholine, and glycerophosphocholine. It is thought that milk choline concentration is influenced by maternal choline intake, and the richest food sources for choline are of animal origin. Scarce information exists on milk choline from countries differing in animal-source food availability. In this secondary analysis of samples from previous trials, the concentrations of the water-soluble forms of choline were quantified by liquid chromatography-tandem mass spectrometry in mature milk samples collected from lactating women in Canada (n = 301 and in Cambodia (n = 67. None of the water-soluble forms of choline concentrations in milk differed between Canada and Cambodia. For all milk samples (n = 368, free choline, phosphocholine, glycerophosphocholine, and the sum of water-soluble forms of choline concentrations in milk were (mean (95%CI 151 (141, 160, 540 (519, 562, 411 (396, 427, and 1102 (1072, 1133 µmol/L, respectively. Theoretically, only 19% of infants would meet the current Adequate Intake (AI for choline. Our findings suggest that the concentrations in milk of water-soluble forms of choline are similar in Canada and Cambodia, and that the concentration used to set the infant AI might be inaccurate.

  16. Concentrations of Water-Soluble Forms of Choline in Human Milk from Lactating Women in Canada and Cambodia.

    Science.gov (United States)

    Wiedeman, Alejandra M; Whitfield, Kyly C; March, Kaitlin M; Chen, Nancy N; Kroeun, Hou; Sokhoing, Ly; Sophonneary, Prak; Dyer, Roger A; Xu, Zhaoming; Kitts, David D; Green, Timothy J; Innis, Sheila M; Barr, Susan I

    2018-03-20

    Choline has critical roles during periods of rapid growth and development, such as infancy. In human milk, choline is mostly present in water-soluble forms (free choline, phosphocholine, and glycerophosphocholine). It is thought that milk choline concentration is influenced by maternal choline intake, and the richest food sources for choline are of animal origin. Scarce information exists on milk choline from countries differing in animal-source food availability. In this secondary analysis of samples from previous trials, the concentrations of the water-soluble forms of choline were quantified by liquid chromatography-tandem mass spectrometry in mature milk samples collected from lactating women in Canada ( n = 301) and in Cambodia ( n = 67). None of the water-soluble forms of choline concentrations in milk differed between Canada and Cambodia. For all milk samples ( n = 368), free choline, phosphocholine, glycerophosphocholine, and the sum of water-soluble forms of choline concentrations in milk were (mean (95%CI)) 151 (141, 160, 540 (519, 562), 411 (396, 427), and 1102 (1072, 1133) µmol/L, respectively. Theoretically, only 19% of infants would meet the current Adequate Intake (AI) for choline. Our findings suggest that the concentrations in milk of water-soluble forms of choline are similar in Canada and Cambodia, and that the concentration used to set the infant AI might be inaccurate.

  17. Choline Autoradiography of Human Prostate Cancer Xenograft: Effect of Castration

    Directory of Open Access Journals (Sweden)

    Hossein Jadvar

    2008-05-01

    Full Text Available The purpose of this study was to investigate the effects of castration and tracer uptake time interval on the level of radiolabeled choline accumulation in murine-implanted human prostate tumor xenografts using quantitative autoradiography. We implanted androgen-dependent (CWR22 and androgen-independent (PC3 human prostate cancer cells in castrated (n = 9 and noncastrated (n = 9 athymic male mice and allowed tumors to grow to 1 cm3. The mice were euthanized at 5, 10, and 20 minutes after injection of 5 µCi [14C]-choline. Mice were prepared for quantitative autoradiography with density light units of viable tumor sections converted to units of radioactivity (nCi/mm2 using calibration. Two-group comparisons were performed using a two-tailed Student t-test with unequal variance and with a significance probability level of less than .05. Two-group comparisons between the means of the tracer uptake level for each tumor type at each of three time points for each of two host types showed that (1 the level of tracer localization in the two tumor types was affected little in relation to the host type and (2 PC3 tumor uptake level tended to increase slowly with time only in the noncastrated host, whereas this was not observed in the castrated host or with CWR22 tumor in either host type. The uptake time interval and castration do not appear to significantly affect the level of radiolabeled choline uptake by the human prostate cancer xenograft.

  18. Blood pressure regulation by CD4+ lymphocytes expressing choline acetyltransferase

    OpenAIRE

    Olofsson, Peder S.; Steinberg, Benjamin E.; Sobbi, Roozbeh; Cox, Maureen A.; Ahmed, Mohamed N.; Oswald, Michaela; Szekeres, Ferenc; Hanes, William M.; Introini, Andrea; Liu, Shu Fang; Holodick, Nichol E.; Rothstein, Thomas L.; L?vdahl, Cecilia; Chavan, Sangeeta S.; Yang, Huan

    2016-01-01

    Blood pressure regulation is known to be maintained by a neuro-endocrine circuit, but whether immune cells contribute to blood pressure homeostasis has not been defined. We previously described that CD4+ T lymphocytes that express choline acetyltransferase (ChAT), which catalyzes the synthesis of the vasorelaxant acetylcholine, relay neural signals 1 . Here we show that these CD4+ CD44high CD62Llow T helper cells by gene expression are a distinct T cell population defined by ChAT (CD4 TChAT)....

  19. Choline Uptake in Agrobacterium tumefaciens by the High-Affinity ChoXWV Transporter▿

    Science.gov (United States)

    Aktas, Meriyem; Jost, Kathinka A.; Fritz, Christiane; Narberhaus, Franz

    2011-01-01

    Agrobacterium tumefaciens is a facultative phytopathogen that causes crown gall disease. For successful plant transformation A. tumefaciens requires the membrane lipid phosphatidylcholine (PC), which is produced via the methylation and the PC synthase (Pcs) pathways. The latter route is dependent on choline. Although choline uptake has been demonstrated in A. tumefaciens, the responsible transporter(s) remained elusive. In this study, we identified the first choline transport system in A. tumefaciens. The ABC-type choline transporter is encoded by the chromosomally located choXWV operon (ChoX, binding protein; ChoW, permease; and ChoV, ATPase). The Cho system is not critical for growth and PC synthesis. However, [14C]choline uptake is severely reduced in A. tumefaciens choX mutants. Recombinant ChoX is able to bind choline with high affinity (equilibrium dissociation constant [KD] of ≈2 μM). Since other quaternary amines are bound by ChoX with much lower affinities (acetylcholine, KD of ≈80 μM; betaine, KD of ≈470 μM), the ChoXWV system functions as a high-affinity transporter with a preference for choline. Two tryptophan residues (W40 and W87) located in the predicted ligand-binding pocket are essential for choline binding. The structural model of ChoX built on Sinorhizobium meliloti ChoX resembles the typical structure of substrate binding proteins with a so-called “Venus flytrap mechanism” of substrate binding. PMID:21803998

  20. 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.

  1. Choline concentrations in human maternal and cord blood and intelligence at 5 y of age.

    Science.gov (United States)

    Signore, Caroline; Ueland, Per Magne; Troendle, James; Mills, James L

    2008-04-01

    Animal studies indicate that maternal prenatal choline supplementation leads to permanent enhancement of attention and spatial memory abilities in offspring, whereas dietary choline restriction during pregnancy impairs cognitive function in offspring. The association between gestational choline concentrations and neurodevelopmental outcome in humans has not been studied. Our objective was to assess the relation between maternal and cord blood choline concentrations and child intelligence quotient (IQ) scores at 5 y of age. With data and samples from a prospective study (n = 404 maternal-child pairs), serum concentrations of free and total choline were measured in maternal serum at 4 gestational age intervals (16-18 wk, 24-26 wk, 30-32 wk, and 36-38 wk) and in cord blood. Child IQ at 5 y of age was assessed with the Wechsler Preschool and Primary Scale of Intelligence-Revised. Multiple regression techniques were used to estimate the relation between choline concentrations and Full Scale IQ, Verbal and Performance IQ, and subscales that assess spatial relation and memory ability while adjusting for other factors that affect IQ. There was no effect at gestational ages 16-18 wk, 24-26 wk, 30-32 wk, and 36-38 wk or in cord blood of serum concentrations of free or total choline on Full Scale child IQ or on selected scales related to visuospatial processing and memory. Gestational and newborn choline concentrations in the physiologic range showed no correlation with childhood intelligence.

  2. Choline Essentiality and Its Requirement in Diets for Juvenile Parrot Fish (

    Directory of Open Access Journals (Sweden)

    Sanaz Khosravi

    2015-05-01

    Full Text Available A 12-wk feeding trial was conducted to evaluate the essentiality of choline supplementation in diets for parrot fish. Five isonitrogenous and isocaloric diets were supplemented with 0 (as control, 500, 1,000, and 2,000 mg choline per kg diet, and a positive control diet without choline contained 0.3% of 2-amino-2-methyl-1-propanol as choline biosynthesis inhibitor (designated as Con, C500, C1000, C2000 and Con+, respectively. Triplicate groups of fish (body weight, 8.8±0.01 g were fed one of the experimental diets at a rate of 4% body weight twice daily. The fish fed Con+ diet revealed significantly lower growth performance and feed utilization efficiency than other fish groups. Supplementation of choline to the basal diet did not significantly influence fish growth. The highest liver lipid content was observed in fish fed the Con+ diet and inversely correlated with liver choline concentration although the differences were not significant. Also, significantly higher liver linoleic, eicosapentaenoic and docosahexaenoic acid contents were found in fish fed the Con+ diet. Innate immune parameters including respiratory burst and myeloperoxidase activities were not significantly affected by dietary choline levels. The findings in this study conclude that choline concentration of approximately 230 mg kg−1 diet meets the requirement of parrot fish.

  3. 75 FR 53577 - Choline hydroxide; Exemption from the Requirement of a Tolerance

    Science.gov (United States)

    2010-09-01

    ... nervous system and memory. Choline is necessary to promote proper development in the fetus and infant and... nervous system and memory. Choline is necessary to promote proper development in the fetus and infant and... infants and children to the pesticide chemical residue in establishing a tolerance and to ``ensure that...

  4. 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...

  5. 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

  6. Enzymatic methods for choline-containing water soluble phospholipids based on fluorescence of choline oxidase: Application to lyso-PAF.

    Science.gov (United States)

    Sanz-Vicente, Isabel; Domínguez, Andrés; Ferrández, Carlos; Galbán, Javier

    2017-02-15

    In this paper we present methods to determine water soluble phospholipids containing choline (wCh-PL). The analytes were hydrolyzed by the enzyme phospholipase D and the choline formed was oxidized by the enzyme Choline Oxidase (ChOx); the fluorescence changes of the ChOx are followed during the enzymatic reaction, avoiding the necessity of an indicating step. Both reactions (hydrolysis and oxidation) can be combined in two different ways: 1) a two-step process (TSP) in which the hydrolysis reaction takes place during an incubation time and then the oxidation reaction is carried out, the analytical signal being provided by the intrinsic fluorescence of ChOx due to tryptophan; 2) a one-step process (OSP) in which both enzymatic reactions are carried out simultaneously in the same test; in this case the analytical signal is provided by the ChOx extrinsic fluorescence due to a fluorescent probe (Ru (II) chelate) linked to the enzyme (ChOx-RuC). The analytical capabilities of these methods were studied using 1,2-dioctanoyl-sn-glycero-3-phosphocholine (C 8 PC), a water soluble short alkyl chain Ch-PL as a substrate, and 1-O-hexadecyl-sn-glyceryl-3-phosphorylcholine (lyso-PAF). The analytical features of merit for both analytes using both methods were obtained. The TSP gave a 10-fold sensitivity and lower quantification limit (1.0*10 -5  M for lyso-PAF), but OSP reduced the determination time and permitted to use the same enzyme aliquot for several measurements. Both methods gave similar precision (RSD 7%, n = 5). The TSP was applied to the determination of C 8 PC and lyso-PAF in spiked synthetic serum matrix using the standard addition method. The application of this methodology to PLD activity determination is also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Moderate Perinatal Choline Deficiency Elicits Altered Physiology and Metabolomic Profiles in the Piglet.

    Directory of Open Access Journals (Sweden)

    Caitlyn M Getty

    Full Text Available Few studies have evaluated the impact of dietary choline on the health and well-being of swine, and those pivotal papers were aimed at determining dietary requirements for sows and growing pigs. This is of importance as the piglet is becoming a widely accepted model for human infant nutrition, but little is known about the impacts of perinatal choline status on overall health and metabolism of the growing piglet. In the present study, sows were provided either a choline deficient (CD, 625 mg choline/kg dry matter or choline sufficient (CS, 1306 mg choline/kg dry matter diet for the last 65 d of gestation (prenatal intervention. Piglets were weaned from the sow 48 h after farrowing and provided either a CD (477 mg choline/kg dry matter or CS (1528 mg choline/kg dry matter milk replacer (postnatal intervention for 29 ± 2 d, resulting in a factorial arrangement of 4 treatment (prenatal/postnatal groups: CS/CS, CS/CD, CD/CS, and CD/CD. Piglet growth was normal for artificially-reared piglets, and was not impacted by perinatal choline status. Piglets receiving the postnatal CD treatment had lower (P < 0.01 plasma choline and choline-containing phospholipid concentrations and higher (P < 0.05 liver enzyme (alkaline phosphatase and gamma-glutamyl transferase values compared with piglets receiving the postnatal CS treatment. Hepatic lipid content of piglets receiving the postnatal CD treatment was higher (P < 0.01 compared with piglets receiving the postnatal CS treatment. Additionally, postnatally CD piglets had lower (P = 0.01 plasma cholesterol than postnatally CS piglets. Brain development was also impacted by perinatal choline status, with brains of piglets exposed to prenatal CD being smaller (P = 0.01 than those of prenatally CS piglets. These findings support the hypothesis that the piglet is a sensitive model for choline deficiency during the perinatal period. In the present study, piglets exhibited similarities in health markers and

  8. Purification of biodiesel by choline chloride based deep eutectic solvent

    Science.gov (United States)

    Niawanti, Helda; Zullaikah, Siti; Rachimoellah, M.

    2017-05-01

    Purification is a crucial step in biodiesel production to meet the biodiesel standard. This study purified biodiesel using choline chloride based deep eutectic solvent (DES). DES was used to reduce unreacted oil and unsaponifiable matter in rice bran oil based biodiesel. The objective of this work was to study the effect of extraction time using DES on the content and yield of fatty acid methyl ester (FAME). Rice bran used in this work contains 16.49 % of oil with initial free fatty acids (FFA) of 44.75 %. Acid catalyzed methanolysis was employed to convert rice bran oil (RBO) into biodiesel under following operation conditions: T = 60 °C, t = 8 h, molar ratio of oil to methanol = 1/10, H2SO4 = 1% w/w of oil. Rice bran oil based biodiesel obtained contain 89.05 % of FAME with very low FFA content (0.05 %). DES was made from a mixture of choline chloride and ethylene glycol with molar ratio of 1/2. Molar ratio of crude biodiesel to DES were 1/2 and 1/4. Extraction time was varied from 15 minutes to 240 minutes at 30 °C. The highest FAME content was obtained after purification for 240 min. at molar ratio crude biodiesel to DES 1/4 was 96.60 %. This work shows that DES has potential to purify biodiesel from non-edible raw material, such as RBO.

  9. Perinatal Choline Supplementation Reduces Amyloidosis and Increases Choline Acetyltransferase Expression in the Hippocampus of the APPswePS1dE9 Alzheimer's Disease Model Mice.

    Directory of Open Access Journals (Sweden)

    Tiffany J Mellott

    Full Text Available Prevention of Alzheimer's disease (AD is a major goal of biomedical sciences. In previous studies we showed that high intake of the essential nutrient, choline, during gestation prevented age-related memory decline in a rat model. In this study we investigated the effects of a similar treatment on AD-related phenotypes in a mouse model of AD. We crossed wild type (WT female mice with hemizygous APPswe/PS1dE9 (APP.PS1 AD model male mice and maintained the pregnant and lactating dams on a control AIN76A diet containing 1.1 g/kg of choline or a choline-supplemented (5 g/kg diet. After weaning all offspring consumed the control diet. As compared to APP.PS1 mice reared on the control diet, the hippocampus of the perinatally choline-supplemented APP.PS1 mice exhibited: 1 altered levels of amyloid precursor protein (APP metabolites-specifically elevated amounts of β-C-terminal fragment (β-CTF and reduced levels of solubilized amyloid Aβ40 and Aβ42 peptides; 2 reduced number and total area of amyloid plaques; 3 preserved levels of choline acetyltransferase protein (CHAT and insulin-like growth factor II (IGF2 and 4 absence of astrogliosis. The data suggest that dietary supplementation of choline during fetal development and early postnatal life may constitute a preventive strategy for AD.

  10. Absolute Quantification of Choline-Related Biomarkers in Breast Cancer Biopsies by Liquid Chromatography Electrospray Ionization Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Maria Chiara Mimmi

    2013-01-01

    Full Text Available It has been repeatedly demonstrated that choline metabolism is altered in a wide variety of cancers. In breast tumours, the choline metabolite profile is characterized by an elevation of phosphocholine and total choline-compounds. This pattern is increasingly being exploited as biomarker in cancer diagnosis.

  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. Protective role of Centella asiatica on lead-induced oxidative stress and suppressed reproductive health in male rats.

    Science.gov (United States)

    Sainath, S B; Meena, R; Supriya, Ch; Reddy, K Pratap; Reddy, P Sreenivasula

    2011-09-01

    Centella asiatica has been mentioned in ancient ayurvedic text of the Indian system of medicine for its properties to promote intelligence. The objective of the present study was to investigate the beneficial effects of C. asiatica on lead-induced oxidative stress and suppressed reproductive performance in male rats. Significant decrease in the weights of testes and epididymis were observed in lead treated animals. Exposure to lead acetate significantly increased malondialdehyde levels with a significant decrease in the superoxide dismutase and catalase activities in the liver, brain, kidneys and testes of rats. Epididymal sperm count, viable sperms, motile sperms and HOS-tail coiled sperms decreased significantly in lead-exposed rats. Testicular steroidogenic enzyme activities also decreased significantly in lead-exposed rats. No significant changes in the selected reproductive variables were observed in the plant extract alone treated rats. Whereas, co-administration of aqueous extracts of C. asiatica to lead exposed rats showed a significant increase in the weights of reproductive organs, reduction in lead-induced oxidative stress in the tissues and improvement in selected reproductive parameters over lead-exposed rats indicating the beneficial role of C. asiatica to counteract lead-induced oxidative stress and to restore the suppressed reproduction in male rats. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Zn2+Induced Irreversible Aggregation, Stacking, and Leakage of Choline Phosphate Liposomes.

    Science.gov (United States)

    Liu, Yibo; Liu, Juewen

    2017-12-19

    The interaction between lipids and metal ions is important for metal sensing, cellular signal transduction, and oxidative lipid damage. While most previous work overlooked the phosphate group of lipids for metal binding, we herein highlight its importance. Phosphocholine (PC) and its headgroup inversed choline phosphate (CP) lipids were used to prepare liposomes. From dynamic light scattering (DLS), Zn 2+ causes significant aggregation or fusion of the CP liposomes, but not PC liposomes. The size change induced by Zn 2+ is not fully reversed by adding EDTA, implying liposome fusion induced by Zn 2+ . Isothermal titration calorimetry (ITC) shows that binding between Zn 2+ and CP liposomes is endothermic with a K d of 110 μM Zn 2+ , suggesting an entropy driven reaction likely due to the release of bound water. In comparison, no heat was detected by titrating Zn 2+ into PC liposomes or Ca 2+ into CP liposomes. Furthermore, Zn 2+ causes a transient leakage of the CP liposomes, and further leakage is observed upon removing Zn 2+ by EDTA. Transmission electron microscopy (TEM) with negative stained samples showed multilamellar CP lipid structures attributable to Zn 2+ sandwiched between lipid bilayers, leading to a proposed reaction mechanism. This work provides an interesting system for studying metal interacting with terminal phosphate groups in liposomes, affecting the size, charge, and membrane integrity of the liposomes.

  14. Protective Effect of Vitamin E Against Lead-induced Memory and Learning Impairment in Male Rats

    Directory of Open Access Journals (Sweden)

    Salehi

    2015-02-01

    Full Text Available Background Lead (Pb2+ is a neurotoxin substance that has been known for its adverse effects on central nervous system and memory. Previous studies reported the potential effect of vitamin E as a memory enhancer. Objectives The purpose of the present study was to assess the protective effects of vitamin E against Pb-induced amnesia. Materials and Methods Forty-eight male Wistar rats (200-250 g were divided equally into the saline, Pb, Pb + vitamin E, and vitamin E alone groups. To induce Pb toxicity, rats received water that contained 0.2% Pb instead of regular water for 1 month. Rats pretreated, treated or post treated with vitamin E (150 mg/kg for 2 months. Passive avoidance learning was assessed using Shuttle-Box after two months. Retention was tested 24 and 48 hours after training. Results The results showed that Pb caused impairment in acquisition and retrieval processes in passive avoidance learning. Vitamin E reversed learning and memory deficits in pre, post or co- exposure with Pb (P < 0.001. Conclusions According to the results of this study, administration of vitamin E to rats counteracts the negative effects of Pb on learning and memory. To more precisely extrapolate these findings to humans, future clinical studies are warranted.

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

    Directory of Open Access Journals (Sweden)

    D P Lippelt

    Full Text Available 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.

  16. 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.

  17. Prenatal-choline supplementation differentially modulates timing of auditory and visual stimuli in aged rats.

    Science.gov (United States)

    Cheng, Ruey-Kuang; Scott, Allison C; Penney, Trevor B; Williams, Christina L; Meck, Warren H

    2008-10-27

    Choline supplementation of the maternal diet has a long-term facilitative effect on the interval-timing ability and temporal memory of the offspring. Here, we examined whether prenatal-choline supplementation has modality-specific effects on duration discrimination in aged (20 mo) male rats. Adult offspring of rats that were given sufficient choline in their chow (CON: 1.1 g/kg) or supplemental choline added to their drinking water (SUP: 3.5 g/kg) during embryonic days (ED) 12-17 were trained and tested on a two-modality (auditory and visual signals) duration bisection procedure (2 s vs. 8 s). Intensity (high vs. low) of the auditory and visual timing signals was systematically manipulated across test sessions such that all combinations of signal intensity by modality were tested. Psychometric response functions indicated that prenatal-choline supplementation systematically increased sensitivity to auditory signals relative to visual signals, thereby magnifying the modality effect that sounds are judged to be longer than lights of equivalent duration. In addition, sensitivity to signal duration was greater in rats given prenatal-choline supplementation, particularly at low intensities of both the auditory and visual signals. Overall, these results suggest that prenatal-choline supplementation impacts interval timing by enhancing the differences in temporal integration between auditory and visual stimuli in aged subjects.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. High dietary choline and betaine intake is associated with low insulin resistance in the Newfoundland population.

    Science.gov (United States)

    Gao, Xiang; Wang, Yongbo; Sun, Guang

    2017-01-01

    Dietary betaine supplement could ameliorate insulin resistance (IR) in animals, but no data are available for choline. Reports on humans are rare. The aim of this study was to investigate the association between dietary choline and betaine intake and IR in humans. We assessed 2394 adults from the CODING (Complex Diseases in the Newfoundland population: Environment and Genetics) study. Intake of dietary choline and betaine was evaluated from the Willett Food Frequency Questionnaire. IR was estimated by homeostatic model assessment (HOMA-IR) and the quantitative insulin-sensitivity check index (QUICKI). Partial correlation analysis was used to determine the correlations of dietary choline and betaine intake with IR adjusted for major confounding factors. Dietary choline and betaine intake was inversely correlated with levels of fasting glucose and insulin, HOMA-IR, HOMA-β (r = -0.08 to -0.27 for choline and r = -0.06 to -0.16 for betaine; P intake, and physical activity level. The significant associations disappeared in men after percent trunk fat was added as a confounding factor. Furthermore, individuals with the highest tertile of dietary choline and betaine intake had the lowest IR severity. Dietary choline and betaine intake, however, was the lowest in the high IR group, intermediate in the medium group, and the highest in the low IR group. This study demonstrated that higher intake of dietary choline and betaine is associated with lower IR in the general population. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Effects of Dietary Methionine Levels on Choline Requirements of Starter White Pekin Ducks

    Directory of Open Access Journals (Sweden)

    Z. G. Wen

    2016-12-01

    Full Text Available A 2×5 factorial experiment, using 2 dietary methionine levels (0.28% and 0.48% and 5 dietary choline levels (0, 394, 823, 1,239, and 1,743 mg/kg, was conducted to study the effects of dietary methionine status on choline requirements of starter white Pekin ducks from 7 to 28 days of age. Four hundred eighty 7-d-old male White Pekin ducks were randomly allotted to ten dietary treatments, each containing 6 replicate pens with 8 birds per pen. At 28 d of age, weight gain, feed intake, and feed/gain were measured and the legs of all ducks from each pen were examined for incidence of perosis. Perosis and growth depression were observed in choline-deficient ducks and supplementation of choline reduced perosis and significantly increased weight gain and feed intake regardless of dietary methionine levels (p<0.05. In addition, significant positive effects of dietary methionine supplementation on weight gain, feed intake, and feed/gain were observed at any choline level (p<0.05. Supplementation of 1,743 mg/kg choline in diets alleviated the depression of weight gain and feed intake caused by methionine deficiency at 0.28% methionine level. The interaction between choline and methionine influenced weight gain and feed intake of ducks (p<0.05. At 0.28% methionine level, 1,743 mg/kg choline group caused 4.92% and 3.23% amount of improvement in weight gain and feed intake compared with 1,239 mg/kg choline group, respectively. According to the broken-line regression, the choline requirements of starter Pekin ducks for weight gain and feed intake were 1,472 and 1,424 mg/kg at 0.28% methionine level and 946 and 907 mg/kg at 0.48% methionine level, respectively. It suggested the choline recommendations of starter Pekin ducks on a semi-purified diet were 1448 mg/kg at 0.28% methionine level and 927 mg/kg at 0.48% methionine level, respectively. Compared with the adequate methionine level, menthionine deficiency markedly increased the choline requirements of

  6. 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

  7. Reverse Osmosis

    Indian Academy of Sciences (India)

    ment of Civil Engineering and is presently the. Chairman of Center for. Sustainable Technologies,. Indian Institute of Science,. Bangalore. His research areas include, unsaturated soil behaviour, hazardous waste management, water quality and remediation of contaminated water. Keywords. Osmosis, reverse osmosis,.

  8. Reversible Sterilization

    Science.gov (United States)

    Largey, Gale

    1977-01-01

    Notes that difficult questions arise concerning the use of sterilization for alleged eugenic and euthenic purposes. Thus, how reversible sterilization will be used with relation to the poor, mentally ill, mentally retarded, criminals, and minors, is questioned. (Author/AM)

  9. No acute effects of choline bitartrate food supplements on memory in healthy, young, human adults

    OpenAIRE

    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 declar...

  10. 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.

  11. 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.

  12. Choline acetyltransferase, acetylcholinesterase, and nicotinic acetylcholine receptors of human gingival and esophageal epithelia.

    Science.gov (United States)

    Nguyen, V T; Hall, L L; Gallacher, G; Ndoye, A; Jolkovsky, D L; Webber, R J; Buchli, R; Grando, S A

    2000-04-01

    A non-neuronal cholinergic system that includes neuronal-like nicotinic acetylcholine receptors (nAChRs) has recently been described in epithelial cells that line the skin and the upper respiratory tract. Since the use of nicotine-containing products is associated with morbidity in the upper digestive tract, and since nicotine may alter cellular functions directly via nAChRs, we sought to identify and characterize a non-neuronal cholinergic system in the gingival and esophageal epithelia. mRNA transcripts for alpha3, alpha5, alpha7, and beta2 nAChR subunits, choline acetyltransferase, and the asymmetric and globular forms of acetylcholinesterase were amplified from gingival keratinocytes (KC) by means of polymerase chain-reactions. These proteins were visualized in the gingival and esophageal epithelia by means of specific antibodies. Variations in distribution and intensity of immunostaining were found, indicating that the repertoire of cholinergic enzymes and receptors expressed by the cells changes during epithelial maturation, and that an upward concentration gradient of free acetylcholine exists. Blocking of the nAChRs with mecamylamine resulted in reversible loss of cell-to-cell adhesion, and shrinking and rounding of cultured gingival KC. Activation of the receptors with acetylcholine or carbachol caused stretching and peripheral ruffling of the cytoplasmic aprons, and formation of new intercellular contacts. These results demonstrate that both the keratinizing epithelium of attached gingiva and the non-keratinizing epithelium lining the upper two-thirds of the esophageal mucosa possess a non-neuronal cholinergic system. The nAChRs expressed by these epithelia are coupled to regulation of cell adhesion and motility, and may provide a target for the deleterious effects of nicotine.

  13. Puerarin protects rat kidney from lead-induced apoptosis by modulating the PI3K/Akt/eNOS pathway

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chan-Min, E-mail: lcm9009@126.com [School of Life Science, Xuzhou Normal University, No.101, Shanghai Road, Tangshan New Area, Xuzhou City 221116, Xuzhou City, Jiangsu Province (China); Ma, Jie-Qiong [School of Chemical Engineering, China University of Mining and Technology, Xuzhou 221008, Xuzhou City, Jiangsu Province (China); Sun, Yun-Zhi [School of Life Science, Xuzhou Normal University, No.101, Shanghai Road, Tangshan New Area, Xuzhou City 221116, Xuzhou City, Jiangsu Province (China)

    2012-02-01

    Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. However, its protective effects against lead (Pb) induced injury in kidney have not been clarified. The aim of the present study was to investigate the effects of puerarin on renal oxidative stress and apoptosis in rats exposed to Pb. Wistar rats were exposed to lead acetate in the drinking water (500 mg Pb/l) with or without puerarin co-administration (100, 200, 300 and 400 mg PU/kg intragastrically once daily) for 75 days. Our data showed that puerarin significantly prevented Pb-induced nephrotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of kidney damage (serum urea, uric acid and creatinine) and histopathological analysis. Moreover, Pb-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of intracellular reduced glutathione (GSH) level in kidney, were suppressed by treatment with puerarin. Furthermore, TUNEL assay showed that Pb-induced apoptosis in rat kidney was significantly inhibited by puerarin. In exploring the underlying mechanisms of puerarin action, we found that activities of caspase-3 were markedly inhibited by the treatment of puerarin in the kidney of Pb-treated rats. Puerarin increased phosphorylated Akt, phosphorylated eNOS and NO levels in kidney, which in turn inactivated pro-apoptotic signaling events including inhibition of mitochondria cytochrome c release and restoration of the balance between pro- and anti-apoptotic Bcl-2 proteins in kidney of Pb-treated rats. In conclusion, these results suggested that the inhibition of Pb-induced apoptosis by puerarin is due at least in part to its antioxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway. Highlights: ► Puerarin prevented lead-induced nephrototoxicity. ► Puerarin reduced lead-induced increase in ROS and TBARS production

  14. 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

  15. Kinetics of [{sup 11}C]choline uptake in prostate cancer: a PET stydy

    Energy Technology Data Exchange (ETDEWEB)

    Sutinen, Eija; Minn, Heikki [Turku PET Centre, Turku University Central Hospital, Turku (Finland); Department of Oncology and Radiotherapy, Turku University Central Hospital, PO Box 52, 20521, Turku (Finland); Nurmi, Martti [Department of Surgery, Turku University Central Hospital, Turku (Finland); Roivainen, Anne; Tolvanen, Tuula; Lehikoinen, Pertti [Turku PET Centre, Turku University Central Hospital, Turku (Finland); Varpula, Matti [Department of Radiology, Turku University Central Hospital, Turku (Finland)

    2004-03-01

    Carbon-11 choline has recently been introduced as a potential tracer for tumour imaging with positron emission tomography (PET). We evaluated the kinetics of the uptake of [{sup 11}C]choline in prostate cancer and benign prostatic hyperplasia. We also evaluated the association between the uptake of [{sup 11}C]choline and the histological grade of malignancy, Gleason score, volume of the prostate and prostate-specific antigen (PSA). Fourteen patients with histologically confirmed prostate cancer and five patients with benign prostatic hyperplasia were studied with [{sup 11}C]choline PET. A mean dose of 430{+-}31 MBq of [{sup 11}C]choline was injected intravenously and a dynamic emission acquisition of prostate was performed for 30 min. The uptake of [{sup 11}C]choline was measured as a standardised uptake value (SUV) and as a kinetic influx constant (K{sub i}) obtained from graphical analysis. Both cancerous and hyperplastic prostate were well visualised with [{sup 11}C]choline against low or moderate tracer accumulation in the bladder and rectal wall. The measured radioactivity in urine was invariably low. In the graphical analysis, linear plots were achieved. The mean K{sub i} of the untreated tumour was 0.205{+-}0.089 min{sup -1} (range 0.128-0.351; n=7) and the mean SUV was 5.6{+-}3.2 (range 1.9-15.5; n=15). K{sub i} values and SUVs correlated closely (r=0.964, P=0.0005), whereas no correlation could be demonstrated between the tumour uptake of [{sup 11}C]choline and the histological grade, Gleason score, volume of the prostate or PSA. The mean SUV and the mean K{sub i} of benign hyperplastic prostate were 3.5{+-}1.0 (range 2.0-4.5; n=4) and 0.119{+-}0.076 min{sup -1} (range 0.065-0.173; n=2). In conclusion, a high uptake of [{sup 11}C]choline characterises not only carcinomatous but also hyperplastic prostatic tissue. Dynamic imaging of the uptake of [{sup 11}C]choline in the prostate shows a good applicability of the graphical analysis model with an

  16. CDP-choline reduces severity of intestinal injury in a neonatal rat model of necrotizing enterocolitis.

    Science.gov (United States)

    Cetinkaya, Merih; Cansev, Mehmet; Cekmez, Ferhat; Tayman, Cuneyt; Canpolat, Fuat Emre; Kafa, Ilker M; Uysal, Sema; Tunc, Turan; Sarici, S Umit

    2013-07-01

    Cytidine 5'-diphosphocholine (CDP-choline) is an endogenous intermediate in the biosynthesis of phosphatidylcholine, a contributor to the mucosal defense of the intestine. The aim of this study was to evaluate the possible cytoprotective effect of CDP-choline treatment on intestinal cell damage, membrane phospholipid content, inflammation, and apoptosis in a neonatal rat model of necrotizing enterocolitis (NEC). We divided a total of 30 newborn pups into three groups: control, NEC, and NEC + CDP-choline. We induced NEC by enteral formula feeding, exposure to hypoxia-hyperoxia, and cold stress. We administered CDP-choline intraperitoneally at 300 mg/kg/d for 3 d starting from the first day of life. We evaluated apoptosis macroscopically and histopathologically in combination with proinflammatory cytokines in the gut samples. Moreover, we determined membrane phospholipid levels as well as activities of xanthine oxidase, superoxide dismutase, glutathione peroxidase, and myeloperoxidase enzymes and the malondialdehyde content of intestinal tissue. Mean clinical sickness score, macroscopic gut assessment score, and intestinal injury score were significantly improved, whereas mean apoptosis score and caspase-3 levels were significantly reduced in pups in the NEC + CDP-choline group compared with the NEC group. Tissue proinflammatory cytokine (interleukin-1β, interleukin-6, and tumor necrosis factor-α) levels as well as tissue malondialdehyde content and myeloperoxidase activities were reduced, whereas glutathione peroxidase and superoxide dismutase activities were preserved in the NEC + CDP-choline group. In addition, NEC damage reduced intestinal tissue membrane phospholipids, whereas CDP-choline significantly enhanced total phospholipid and phosphatidylcholine levels. Long-term follow-up in additional experiments revealed increased body weight, decreased clinical sickness scores, and enhanced survival in CDP-choline-receiving versus saline-receiving pups with NEC

  17. 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

  18. 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

  19. 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.)

  20. Comparison of radiolabeled choline and ethanolamine as probe for cancer detection.

    Science.gov (United States)

    Mintz, Akiva; Wang, Limin; Ponde, Datta E

    2008-05-01

    Recently [11C] or [18F] labeled choline has been developed as a promising tracer for cancer detection. However choline may not be best agent, as the development of in vivo 1H-decoupled, NOE-enhanced 31P- MRS enabled the resolution of the resonances of phosphorylethanolamine (PEt) and phosphorylcholine (PCho) peaks that normally overlap under the broad phosphomonoester peak (PME). In human non-Hodgkin's lymphoma in vivo, the PEt/PCho ratio was reported as 2.9 +/- 1.0 (n = 11). The objective of this work was to compare radiolabeled choline with ethanolamine as an agent for cancer detection using various cancer cell lines. Cell uptake of [14C] ethanolamine and [14C] N, N'-dimethyl ethanolamine was compared to [14C] choline uptake in a wide variety of different cancer cell lines. Our data clearly demonstrates that, ethanolamine and N, N'-dimethyl ethanolamine showed 2-7 fold more uptake than choline. We showed that proliferating fibroblasts have significantly higher uptake of ethanolamine and N, N'-dimethyl-ethanolamine, than does growth arrested fibroblasts. Time course studies in A172 cells indicate continuous linear uptake of ethanolamine after four hours of tracer exposure, which was halted if tracer containing, media was replaced with regular media after one hour. The androgen stimulated and depleted study with prostate cancer cell lines showed that increased trapping of radiotracers in cells is well correlated with their proliferation status. We carried out comparison of radiolabeled choline and ethanolamine by cell uptake study using 8 different cancer cell lines. To evaluate the response of radiotracers towards proliferation we also carried out their cell uptake study of androgen dependent and androgen independent cells in androgen stipulated and deprived media. Our data demonstrate that ethanolamine and N, N'-dimethyl ethanolamine are taken up by a wide variety of tumor cells significantly better (2-7 fold) than the clinically utilized radiolabeled choline

  1. The effect of centrally injected CDP-choline on respiratory system; involvement of phospholipase to thromboxane signaling pathway.

    Science.gov (United States)

    Topuz, Bora B; Altinbas, Burcin; Yilmaz, Mustafa S; Saha, Sikha; Batten, Trevor F; Savci, Vahide; Yalcin, Murat

    2014-05-01

    CDP-choline is an endogenous metabolite in phosphatidylcholine biosynthesis. Exogenous administration of CDP-choline has been shown to affect brain metabolism and to exhibit cardiovascular, neuroendocrine neuroprotective actions. On the other hand, little is known regarding its respiratory actions and/or central mechanism of its respiratory effect. Therefore the current study was designed to investigate the possible effects of centrally injected CDP-choline on respiratory system and the mediation of the central cholinergic receptors and phospholipase to thromboxane signaling pathway on CDP-choline-induced respiratory effects in anaesthetized rats. Intracerebroventricularly (i.c.v.) administration of CDP-choline induced dose- and time-dependent increased respiratory rates, tidal volume and minute ventilation of male anaesthetized Spraque Dawley rats. İ.c.v. pretreatment with atropine failed to alter the hyperventilation responses to CDP-choline whereas mecamylamine, cholinergic nicotinic receptor antagonist, mepacrine, phospholipase A2 inhibitor, and neomycin phospholipase C inhibitor, blocked completely the hyperventilation induced by CDP-choline. In addition, central pretreatment with furegrelate, thromboxane A2 synthesis inhibitor, also partially blocked CDP-choline-evoked hyperventilation effects. These data show that centrally administered CDP-choline induces hyperventilation which is mediated by activation of central nicotinic receptors and phospholipase to thromboxane signaling pathway. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Reverse Osmosis

    Indian Academy of Sciences (India)

    or the water reaches the tip of every leaf of a plant is due to osmotic pressure. ... concentration and temperature of the solution by a law that is similar to the gas law. ... waste management, water quality and remediation of contaminated water. Keywords. Osmosis, reverse osmosis, desalinatiion, seawater, water purification.

  3. 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

  4. 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

  5. Intravenous CDP-choline activates neurons in supraoptic and paraventricular nuclei and induces hormone secretion.

    Science.gov (United States)

    Eyigor, Ozhan; Coskun, Cenk; Cavun, Sinan; Savci, Vahide

    2012-02-10

    The aim of the present study was to assess the effects of intravenous (i.v.) cytidine-5'-diphosphate (CDP)-choline administration on the activation of oxytocin and vasopressin neurons in the supraoptic (SON) and paraventricular nuclei (PVN), using the immunohistochemical identification of c-Fos expression as a marker of neuronal activation and to correlate this with the plasma hormone levels. Rats were catheterized under sevofluorane anesthesia and experiments were conducted 24h later. Blood samples were withdrawn from arterial catheter at 2, 5, 10, 20, 40 and 60 min after CDP-choline (0.5, 1.0 and 2.0 g/kg; i.v.) or saline (1.0 ml/kg; i.v.) for the measurement of plasma oxytocin and vasopressin levels by radioimmunoassay. Animals were sacrificed 90 min after CDP-choline administration for dual immunohistochemistry which was performed on paraformaldehyde-fixed vibratome sections. Dual immunohistochemistry for c-Fos and oxytocin or vasopressin revealed that CDP-choline activates these neurons in a dose-dependent manner. Light microscopic analyses showed that, about 41%, 75% or 87% of the oxytocin neurons and about 18%, 46% or 82% of the vasopressin neurons in SON express c-Fos, thus activated, by the dosages of 0.5, 1.0 or 2.0 g/kg CDP-choline, respectively. Increases in c-Fos expression were about 29%, 62% or 81% for the oxytocin neurons and about 38%, 70% or 78% for the vasopressin neurons in PVN with the dosages of 0.5, 1.0 or 2.0 g/kg CDP-choline, respectively. When compared to the control groups (8% and 7% oxytocin or 2% and 5% vasopressin neuronal activation in SON or PVN, respectively), these increases were found to be statistically significant (p<0.05). In the PVN most of the magnocellular neurons were activated while less number of parvocellular neurons expressed c-Fos in response to CDP-choline challenge. In correlation with c-Fos data, CDP-choline increased plasma oxytocin and vasopressin levels both dose- and time-dependently. Results of the present

  6. Choline Intake and Its Food Sources in the Diet of Romanian Kindergarten Children.

    Science.gov (United States)

    Reinhard Prelicz, Cristian; Lotrean, Lucia Maria

    2017-08-18

    The objective of this study is to assess the usual intake and food sources of choline in a group of Romanian kindergarten children. A cross-sectional study was performed among 71 children aged 4-6 years from four kindergartens from Cluj-Napoca, Romania. Dietary intake data were collected by means of three-day food records. The mean (SD) daily intake of choline was 215 (32) mg/day, 22.5% of the participants fulfilling the adequate intake (AI) for children 4-6 years of age of 250 mg of choline per day. The main food sources were meat (mainly poultry), eggs, grains, cereals, and baked products (mainly bread), and dairy products (mainly milk). The results of the logistic regression analyses show that an appropriate consumption of choline/day was statistically significantly associated with the consumption of at least one egg per three days (OR = 7.5, p cheese/day) (OR = 4.4, p < 0.05), and at least one portion of meat/day (90 g/day) (OR = 14.4, p < 0.05). The results underline the need for future surveys in this field, as well as actions to encourage an appropriate diet for children, including an appropriate content of choline.

  7. 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.

  8. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit...... by accounting for the significance of the materials and the equipment that enters into the production of statistics. Key words: Reversible statistics, diverse materials, constructivism, economics, science, and technology....

  9. 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.

  10. 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

  11. Influence of minerals on lead-induced alterations in liver function in rats exposed to long-term lead exposure

    International Nuclear Information System (INIS)

    Herman, D'souza Sunil; Geraldine, Menezes; T, Venkatesh

    2009-01-01

    The objective of this study was to evaluate the role of minerals on lead-induced effect on the liver. Differentiation of minerals and heavy metals pose an inherent problem due to certain common properties shared by them. With this approach to the problem of heavy metal toxicity, in the present study two groups of male Wistar albino rats, one group (well-nourished) fed on mineral rich diet and other group (undernourished) fed on diet without mineral supplements were used. Both the groups of rats were subjected to long-term lead exposure. The diet of well-nourished group was supplemented with calcium (Ca); 1.2%, phosphorous (P); 0.6%, iron (Fe); 90 mg/kg, zinc (Zn); 50 mg/kg, magnesium (Mg); 0.08%, manganese (Mn); 70 mg/kg, selenium (Se); 0.2 mg/kg, copper (Cu); 5 mg/kg, molybdenum (Mo); 0.8 mg/kg, iodine (I); 0.6 mg/kg, cobalt (Co); 3.0 mg/kg. Their blood lead and parameters of liver function were monitored periodically. Results of the study showed a very high statistically significant increase (p < 0.001) in the blood lead (PbB) levels and liver function test parameters in the undernourished subjects compared to the well-nourished subjects. Nutritional management of lead poisoning is of importance since essential elements and toxic heavy metals may interact to minimize the absorption of lead.

  12. Prostate cancer: concordance between 18F-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

  13. 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.

  14. HDAC inhibition induces increased choline uptake and elevated phosphocholine levels in MCF7 breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Christopher S Ward

    Full Text Available Histone deacetylase (HDAC inhibitors have emerged as effective antineoplastic agents in the clinic. Studies from our lab and others have reported that magnetic resonance spectroscopy (MRS-detectable phosphocholine (PC is elevated following SAHA treatment, providing a potential noninvasive biomarker of response. Typically, elevated PC is associated with cancer while a decrease in PC accompanies response to antineoplastic treatment. The goal of this study was therefore to elucidate the underlying biochemical mechanism by which HDAC inhibition leads to elevated PC. We investigated the effect of SAHA on MCF-7 breast cancer cells using (13C MRS to monitor [1,2-(13C] choline uptake and phosphorylation to PC. We found that PC synthesis was significantly higher in treated cells, representing 154±19% of control. This was within standard deviation of the increase in total PC levels detected by (31P MRS (129±7% of control. Furthermore, cellular choline kinase activity was elevated (177±31%, while cytidylyltransferase activity was unchanged. Expression of the intermediate-affinity choline transporter SLC44A1 and choline kinase α increased (144% and 161%, respectively relative to control, as determined by mRNA microarray analysis with protein-level confirmation by Western blotting. Taken together, our findings indicate that the increase in PC levels following SAHA treatment results from its elevated synthesis. Additionally, the concentration of glycerophosphocholine (GPC increased significantly with treatment to 210±45%. This is likely due to the upregulated expression of several phospholipase A2 (PLA2 isoforms, resulting in increased PLA2 activity (162±18% in SAHA-treated cells. Importantly, the levels of total choline (tCho-containing metabolites, comprised of choline, PC and GPC, are readily detectable clinically using (1H MRS. Our findings thus provide an important step in validating clinically translatable non-invasive imaging methods for follow

  15. Human TMEM30a promotes uptake of antitumor and bioactive choline phospholipids into mammalian cells.

    Science.gov (United States)

    Chen, Rui; Brady, Erin; McIntyre, Thomas M

    2011-03-01

    Antitumor alkylphospholipids initiate apoptosis in transformed HL-60 and Jurkat cells while sparing their progenitors. 1-O-Alkyl-2-carboxymethyl-sn-glycero-3-phosphocholine (Edelfosine) like other short-chained phospholipids--inflammatory platelet-activating factor (PAF) and apoptotic oxidatively truncated phospholipids--are proposed to have intracellular sites of action, yet a conduit for these choline phospholipids into mammalian cells is undefined. Edelfosine is also accumulated by Saccharomyces cerevisiae in a process requiring the membrane protein Lem3p, and the human genome contains a Lem3p homolog TMEM30a. We show that import of choline phospholipids into S. cerevisiae ΔLem3 is partially reconstituted by human TMEM30a and by Lem3p-TMEM30a chimeras, showing the proteins are orthologous. TMEM30a-GFP chimeras expressed in mammalian cells localized in plasma membranes, as well as internal organelles, and ectopic TMEM30a expression promoted uptake of exogenous choline and ethanolamine phospholipids. Short hairpin RNA knockdown of TMEM30a reduced fluorescent choline phospholipid and [(3)H]PAF import. This knockdown also reduced mitochondrial depolarization from exogenous Edelfosine or the mitotoxic oxidatively truncated phospholipid azelaoyl phosphatidylcholine, and the knockdown reduced apoptosis in response to these two phospholipids. These results show that extracellular choline phospholipids with short sn-2 residues can have intracellular roles and sites of metabolism because they are transport substrates for a TMEM30a phospholipid import system. Variation in this mechanism could limit sensitivity to short chain choline phospholipids such as Edelfosine, PAF, and proapoptotic phospholipids.

  16. 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...

  17. 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...

  18. Improved human visuomotor performance and pupil constriction after choline supplementation in a placebo-controlled double-blind study

    NARCIS (Netherlands)

    Naber, M.; Hommel, Bernhard; Colzato, Lorenza

    2015-01-01

    Only few nutrients are known to enhance cognition. Here we explore whether visuomotor performance can be improved through the intake of the nutrient choline, an essential chemical compound in a vertebrate’s diet. Choline is abundant in for example eggs and shrimps and many animal studies suggest

  19. 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...

  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 molecular imaging with small-animal PET for monitoring tumor cellular response to photodynamic therapy of cancer

    Science.gov (United States)

    Fei, Baowei; Wang, Hesheng; Wu, Chunying; Meyers, Joseph; Xue, Liang-Yan; MacLennan, Gregory; Schluchter, Mark

    2009-02-01

    We are developing and evaluating choline molecular imaging with positron emission tomography (PET) for monitoring tumor response to photodynamic therapy (PDT) in animal models. Human prostate cancer (PC-3) was studied in athymic nude mice. A second-generation photosensitizer Pc 4 was used for PDT in tumor-bearing mice. MicroPET images with 11C-choline were acquired before PDT and 48 h after PDT. Time-activity curves of 11C-choline uptake were analyzed before and after PDT. For treated tumors, normalized choline uptake decreased significantly 48 h after PDT, compared to the same tumors pre-PDT (p PET imaging with 11C-choline is sensitive to detect early tumor response to PDT in the animal model of human prostate cancer.

  2. 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...

  3. Neural restrictive silencer factor and choline acetyltransferase expression in cerebral tissue of Alzheimer’s Disease patients: A pilot study

    Science.gov (United States)

    González-Castañeda, Rocío E.; Sánchez-González, Víctor J.; Flores-Soto, Mario; Vázquez-Camacho, Gonzalo; Macías-Islas, Miguel A.; Ortiz, Genaro G.

    2013-01-01

    Decreased Choline Acetyltransferase (ChAT) brain level is one of the main biochemical disorders in Alzheimer’s Disease (AD). In rodents, recent data show that the CHAT gene can be regulated by a neural restrictive silencer factor (NRSF). The aim of the present work was to evaluate the gene and protein expression of CHAT and NRSF in frontal, temporal, entorhinal and parietal cortices of AD patient brains. Four brains from patients with AD and four brains from subjects without dementia were studied. Cerebral tissues were obtained and processed by the guanidine isothiocyanate method for RNA extraction. CHAT and NRSF gene and protein expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. CHAT gene expression levels were 39% lower in AD patients as compared to the control group (p 0.05, U test) than in the control subjects. These findings suggest for the first time that in the brain of AD patients high NRSF protein levels are related to low CHAT gene expression levels. PMID:23569405

  4. Partial prevention of long-term femoral bone loss in aged ovariectomized rats supplemented with choline-stabilized orthosilicic acid.

    Science.gov (United States)

    Calomme, M; Geusens, P; Demeester, N; Behets, G J; D'Haese, P; Sindambiwe, J B; Van Hoof, V; Vanden Berghe, D

    2006-04-01

    Silicon (Si) deficiency in animals results in bone defects. Choline-stabilized orthosilicic acid (ch-OSA) was found to have a high bioavailability compared to other Si supplements. The effect of ch-OSA supplementation was investigated on bone loss in aged ovariectomized (OVX) rats. Female Wistar rats (n = 58, age 9 months) were randomized in three groups. One group was sham-operated (sham, n = 21), and bilateral OVX was performed in the other two groups. OVX rats were supplemented orally with ch-OSA over 30 weeks (OVX1, n = 20; 1 mg Si/kg body weight daily) or used as controls (OVX0, n = 17). The serum Si concentration and the 24-hour urinary Si excretion of supplemented OVX rats was significantly higher compared to sham and OVX controls. Supplementation with ch-OSA significantly but partially reversed the decrease in Ca excretion, which was observed after OVX. The increase in bone turnover in OVX rats tended to be reduced by ch-OSA supplementation. ch-OSA supplementation increased significantly the femoral bone mineral content (BMC) in the distal region and total femoral BMC in OVX rats, whereas lumbar BMC was marginally increased. Femoral BMD was significantly increased at two sites in the distal region in OVX rats supplemented with ch-OSA compared to OVX controls. Total lumbar bone mineral density was marginally increased by ch-OSA supplementation. In conclusion, ch-OSA supplementation partially prevents femoral bone loss in the aged OVX rat model.

  5. Hydroalcoholic seed extract of Coriandrum sativum (Coriander) alleviates lead-induced oxidative stress in different regions of rat brain.

    Science.gov (United States)

    Velaga, Manoj Kumar; Yallapragada, Prabhakara Rao; Williams, Dale; Rajanna, Sharada; Bettaiya, Rajanna

    2014-06-01

    Lead exposure is known to cause apoptotic neurodegeneration and neurobehavioral abnormalities in developing and adult brain by impairing cognition and memory. Coriandrum sativum is an herb belonging to Umbelliferae and is reported to have a protective effect against lead toxicity. In the present investigation, an attempt has been made to evaluate the protective activity of the hydroalcoholic extract of C. sativum seed against lead-induced oxidative stress. Male Wistar strain rats (100-120 g) were divided into four groups: control group: 1,000 mg/L of sodium acetate; exposed group: 1,000 mg/L lead acetate for 4 weeks; C. sativum treated 1 (CST1) group: 250 mg/kg body weight/day for seven consecutive days after 4 weeks of lead exposure; C. sativum treated 2 (CST2) group: 500 mg/kg body weight/day for seven consecutive days after 4 weeks of lead exposure. After the exposure and treatment periods, rats were sacrificed by cervical dislocation, and the whole brain was immediately isolated and separated into four regions: cerebellum, hippocampus, frontal cortex, and brain stem along with the control group. After sacrifice, blood was immediately collected into heparinized vials and stored at 4 °C. In all the tissues, reactive oxygen species (ROS), lipid peroxidation products (LPP), and total protein carbonyl content (TPCC) were estimated following standard protocols. An indicator enzyme for lead toxicity namely delta-amino levulinic acid dehydratase (δ-ALAD) activity was determined in the blood. A significant (psativum resulted in a tissue-specific amelioration of oxidative stress produced by lead.

  6. A study of chemopreventive effects of Emblica officinalis Linn. against radiation and lead induced haematological changes in Swiss albino mice

    International Nuclear Information System (INIS)

    Halduniya, Hanish K.; Singariya, Seema; Bhatnagar, Shruti; Srivasrava, Deepti; Agarwal, Manisha

    2012-01-01

    The vast potential of radiant energy opens vistas of new horizons as its use in various fields of science, technology, therapeutics and diagnosis. However its also exposes the global population to the hazards of nuclear accidents and radiation injury. In this era of nuclear science it has become a prerequisite to know the effects of radiation on mankind and to develop effective countermeasures for minimizing the damages of radiation exposure. Heavy metals like lead can cause deleterious effects when its concentration goes beyond the limit in ecosystem. The combined effects of radiation and lead further increases the causation of damages to organs and tissues. Amla is found to be a non toxic, inexpensive, easily available herbal drug. Therefore present study was pertain to evaluate the chemo preventive role of Amla against radiation and lead induced changes in blood of Swiss albino mice. The animals were exposed to 6.0 Gy of gamma rays and with or without lead acetate which was given to them adlibitum. The Emblica was administered seven days prior to irradiation or lead acetate treatment. Three animals were sacrificed from all the experimental group at each post treatment intervals of 1, 2, 4, 7, 14 and 28 days by cervical dislocation . The blood was collected in heparinised tube for estimating various haematological parameters. The value of RBC, WBC, PCV, Hemoglobin, and MCV decreased up to day-14 in non drug treated groups and day-7 in drug treated groups, thereafter the value increased. When the animals treated with radiation and lead simultaneously synergistic effects were observed. The Amla treated groups showed early and fast recovery thus, it may deduce from above observation that Amla has potential to check the alteration produced by radiation and lead in the blood of Swiss albino mice. (author)

  7. Protective efficacy of Emblica against radiation and lead induced changes in the Jejunum of Swiss Albino mice

    International Nuclear Information System (INIS)

    Purohit, R.K.; Meena, Dinesh; Issran, Rakesh; Pyarelal; Jangir, Ashok Kumar

    2014-01-01

    Recently, increased interest has developed on search for potential drugs of plant origin which can quench the radiation induced free radicals and eliminate oxygen with minimum side effects. In view of the fact, present study was planned to evaluate the protective efficacy of Emblica against radiation and lead induced changes in jejunum of mice. For the purpose, six to eight weeks old male Swiss albino mice were selected and divided into seven groups on the basis of radiation, lead, combined treatment and drug treated. The values of total proteins, cholesterol, acid phosphatase activity, alkaline phosphatase activity, DNA and RNA were estimated. The values of total proteins, cholesterol, DNA and RNA decreased whereas acid phosphatase and alkaline phosphatase activity increased. After irradiation with various doses of gamma rays, histological changes depend upon the dose of radiation delivered. The important radio-lesions were looseness of musculatrue, hydropic degeneration in submucosa and lamina propria, hyperaemia and haemorrhage in submucosa, pyknotic cells, cytoplasmic degranulation and vacuolation, abnormal mitotic figures. Karyolysis, karyorrhexis and chromatolysis were also observed in crypt cells. Shortening and breaking of villus tips, leucocytic infiltration in lamina propria and cell debris in intestinal lumen were also noted. The number of goblet cells per crypt section also decreased in all the experimental groups. The value of the experimental groups was significantly lower than that of the control group. The biochemical finding indicated the drug treated section of living tissue showed slightly/no degenerative changes. The drug treated groups demonstrating the ability of Aloe vera to inhibit oxidative stress thus preventing tissue injury. (author)

  8. Melatonin Protects Cultured Tobacco Cells against Lead-Induced Cell Death via Inhibition of Cytochrome c Translocation

    Directory of Open Access Journals (Sweden)

    Agnieszka Kobylińska

    2017-09-01

    Full Text Available Melatonin was discovered in plants more than two decades ago and, especially in the last decade, it has captured the interests of plant biologists. Beyond its possible participation in photoperiod processes and its role as a direct free radical scavenger as well as an indirect antioxidant, melatonin is also involved in plant defense strategies/reactions. However, the mechanisms that this indoleamine activates to improve plant stress tolerance still require identification and clarification. In the present report, the ability of exogenous melatonin to protect Nicotiana tabacum L. line Bright Yellow 2 (BY-2 suspension cells against the toxic exposure to lead was examined. Studies related to cell proliferation and viability, DNA fragmentation, possible translocation of cytochrome c from mitochondria to cytosol, cell morphology after fluorescence staining and also the in situ accumulation of superoxide radicals measured via the nitro blue tetrazolium reducing test, were conducted. This work establishes a novel finding by correcting the inhibition of release of mitochondrial ctytocrome c in to the cytoplasm with the high accumulation of superoxide radicals. The results show that pretreatment with 200 nm of melatonin protected tobacco cells from DNA damage caused by lead. Melatonin, as an efficacious antioxidant, limited superoxide radical accumulation as well as cytochrome c release thereby, it likely prevents the activation of the cascade of processes leading to cell death. Fluorescence staining with acridine orange and ethidium bromide documented that lead-stressed cells additionally treated with melatonin displayed intact nuclei. The results revealed that melatonin at proper dosage could significantly increase BY-2 cell proliferation and protected them against death. It was proved that melatonin could function as an effective priming agent to promote survival of tobacco cells under harmful lead-induced stress conditions.

  9. Protective efficacy of Emblica against radiation and lead induced biochemical changes in the kidney of Swiss albino mice

    International Nuclear Information System (INIS)

    Chakrawarti, Aruna; Dev, Rahul; Rathore, Narendra Singh; Khatri, Anand

    2012-01-01

    Ionizing radiation kills cells in the area being treated (the target tissue) as well as other surrounding healthy cells. The damaging effects of ionizing radiation on healthy tissue create a major barrier in effective treatment of common human cancers. Thus there is a need to find a safe and highly effective avenue to reduce normal cell damage during cancer therapy, plants have been used in the traditional healthcare system from time immemorial, and phyto products continue to play an essential role in medicine. Emblica, is reported to have an excellent radio protective activity, antioxidant and a free radical scavenger. In light of above, the present study was aimed to evaluate the protective effect of Emblica against radiation and lead induced biochemical alterations in the kidney of Swiss albino mice. The animals were exposed to 6.0 Gy of gamma rays with or without Lead acetate treatment. The Emblica was administered seven days prior to irradiation or Lead Acetate treatment. The animals from all experimental groups were sacrificed by cervical dislocation at each post treatment intervals of 1, 2, 4, 7, 14 and 28 days. After sacrificing the animals, pieces of the kidney were taken out and kept at - 20 deg C for different biochemical parameters. For the study the animals were exposed to 6.0 Gy of gamma rays with or without Lead acetate treatments. In the experimental groups the Emblica juice was given seven days prior to the radiation or lead acetate treatment. The various biochemical parameters viz, total proteins, glycogen, cholesterol, acid phosphatase and alkaline phosphatase activities, DNA and RNA were estimated. The values were observed in the form of increase or decrease. After combined treatment of radiation and lead acetate the changes were more severe showing synergistic effect of both the agent. An early and fast recovery was also noticed in Emblica pre-treated animals. Thus it appears that Emblica is potent enough to check Lead and Radiation induced

  10. Hepatoprotective efficacy of Spirulina platensis against lead-induced oxidative stress and genotoxicity in catfish; Clarias gariepinus.

    Science.gov (United States)

    Sayed, Alaa El-Din H; El-Sayed, Yasser S; El-Far, Ali H

    2017-09-01

    Lead (Pb) is a toxic environmental pollutant that induces a broad range of biochemical and physiological hazards in living organisms. We investigated the possible hepatoprotective effects of Spirulina platensis (SP) in counteracting the Pb-induced oxidative damage. Ninety-six adult African catfish were allocated into four equal groups. The 1st group (control) fed basal diet while the 2nd group (Pb-treated) fed on basal diet and exposed to 1mg Pb(NO 3 ) 2 /L. The 3rd and 4th groups fed SP-supplemented basal diets at levels of 0.25% and 0.5%, respectively and exposed to Pb. Serum samples were used to analyze hepatic function biomarkers, electrolytes, and oxidant and antioxidant status. Lipid peroxidation and DNA fragmentation were determined in the liver tissues. Pb exposure induced hepatic dysfunction, electrolytes (Na + , K + , Ca +2 , and Cl - ) imbalance, as well a significant decrease in GSH content, and LDH, AChE, SOD, CAT and GST enzymes activity. SP supplementation reverted these biochemical and genetic alterations close to control levels. This amelioration was higher with 0.5% SP and at the 4th week of exposure, showing concentration- and time-dependency. Thus, the current study suggests that SP could protect the catfish liver against lead-induced injury by scavenging ROS, sustaining the antioxidant status and diminishing DNA oxidative damage. The dietary inclusion of SP can be used as a promising protective agent to counteract oxidative stress-mediated diseases and toxicities. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit...... in different ways. The presence and absence of diverse materials, both natural and political, is what distinguishes them from each other. Arguments are presented for a more symmetric relation between the scientific statistical text and the reader. I will argue that a more symmetric relation can be achieved...

  12. Lewis acidic (choline chloride. 3ZnCl 2) ionic liquid: A green and ...

    Indian Academy of Sciences (India)

    Abstract. A green and convenient procedure for the one-pot multicomponent synthesis of 4-((3-indolyl)(aryl)methyl)-N,N-dimethylanilines using (choline chloride.3ZnCl2) ionic liquid as catalyst, at 100°C and under solvent-free condition is described. Utilizing environmentally benign reagents, elimination of organic solvents, ...

  13. Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease

    NARCIS (Netherlands)

    Bertoia, Monica L.; Pai, Jennifer K.; Cooke, John P.; Joosten, Michel M.; Mittleman, Murray A.; Rimm, Eric B.; Mukamal, Kenneth J.

    Objective: Few studies have examined the roles of homocysteine and related nutrients in the development of peripheral artery disease (PAD). We examined the associations between plasma homocysteine, dietary B vitamins, betaine, choline, and supplemental folic acid use and incidence of PAD. Methods:

  14. 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.

  15. 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.

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

    Indian Academy of Sciences (India)

    M P PADMA PRIYA

    2018-03-21

    Mar 21, 2018 ... This Bronsted acidic choline chloride-butane sultone-based ionic liquid was highly selective towards the conversion of cumene hydroperoxide to phenol. Ease of use and recovery, low environmental impact, and effective reduction of activation energy make it a potential candidate for industrial production of ...

  17. 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.

  18. 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.

  19. 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 ... Effect of herbal choline and rumen-protected methionine on lamb performance and ... successful, presumably because the diets were based on low-quality forage with inadequate lysine (Lys) and ... experiments with dairy cows showed that dietary supplementation with RPM and RPC alleviated negative ...

  20. 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

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

    Science.gov (United States)

    Lee, Jung Eun; Jacques, Paul F; Dougherty, Lauren; Selhub, Jacob; Giovannucci, Edward; Zeisel, Steven H; Cho, Eunyoung

    2010-05-01

    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, assessed from food-frequency questionnaires, are associated with total plasma homocysteine concentrations under both fasting and post-methionine-load conditions in both pre- and post-folic acid fortification periods in the United States. We assessed the association between choline and betaine intakes and fasting and post-methionine-load homocysteine concentrations using the US Department of Agriculture revised food-composition tables and evaluated whether the associations varied by folic acid fortification periods in 1325 male and 1407 female participants in the sixth examination (1995-1998) of the Framingham Offspring Study. A higher choline-plus-betaine intake was associated with lower concentrations of post-methionine-load homocysteine; the multivariate geometric means were 24.1 micromol/L (95% CI: 23.4, 24.9 micromol/L) in the top quintile of intake and 25.0 micromol/L (95% CI: 24.2, 25.7 micromol/L) in the bottom quintile (P for trend = 0.01). We found an inverse association between choline-plus-betaine intake and fasting homocysteine concentrations; the multivariate geometric mean fasting homocysteine concentrations were 9.6 micromol/L (95% CI: 9.3, 9.9 micromol/L) in the top quintile and 10.1 micromol/L (95% CI: 9.8, 10.4 micromol/L) in the bottom quintile (P for trend intake and either fasting or post-methionine-load homocysteine was no longer present. Choline and betaine intakes were associated with both fasting and post-methionine-load total homocysteine concentrations, especially in participants with low folate and vitamin B-12 status. The inverse association between choline and betaine intakes and homocysteine concentrations was no longer present in the

  2. Are dietary choline and betaine intakes determinants of total homocysteine concentration?1234

    Science.gov (United States)

    Lee, Jung Eun; Jacques, Paul F; Dougherty, Lauren; Selhub, Jacob; Giovannucci, Edward; Zeisel, Steven H

    2010-01-01

    Background: 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. Objective: The objective was to examine whether choline and betaine intakes, assessed from food-frequency questionnaires, are associated with total plasma homocysteine concentrations under both fasting and post–methionine-load conditions in both pre– and post–folic acid fortification periods in the United States. Design: We assessed the association between choline and betaine intakes and fasting and post–methionine-load homocysteine concentrations using the US Department of Agriculture revised food-composition tables and evaluated whether the associations varied by folic acid fortification periods in 1325 male and 1407 female participants in the sixth examination (1995–1998) of the Framingham Offspring Study. Results: A higher choline-plus-betaine intake was associated with lower concentrations of post–methionine-load homocysteine; the multivariate geometric means were 24.1 μmol/L (95% CI: 23.4, 24.9 μmol/L) in the top quintile of intake and 25.0 μmol/L (95% CI: 24.2, 25.7 μmol/L) in the bottom quintile (P for trend = 0.01). We found an inverse association between choline-plus-betaine intake and fasting homocysteine concentrations; the multivariate geometric mean fasting homocysteine concentrations were 9.6 μmol/L (95% CI: 9.3, 9.9 μmol/L) in the top quintile and 10.1 μmol/L (95% CI: 9.8, 10.4 μmol/L) in the bottom quintile (P for trend intake and either fasting or post–methionine-load homocysteine was no longer present. Conclusions: Choline and betaine intakes were associated with both fasting and post–methionine-load total homocysteine concentrations, especially in participants with low folate and vitamin B-12 status. The inverse association between choline and betaine intakes and homocysteine

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

    Science.gov (United States)

    Supriyati; Budiarsana, I Gusti Made; Praharani, Lisa; Krisnan, Rantan; Sutama, I Ktut

    2016-01-01

    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. 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. 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 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 composition percentage and milk constituent yields improved significantly (p conversion ratio and

  4. 1,2-Diacylglycerol choline phosphotransferase catalyzes the final step in the unique Treponema denticola phosphatidylcholine biosynthesis pathway.

    Science.gov (United States)

    Vences-Guzmán, Miguel Ángel; Paula Goetting-Minesky, M; Guan, Ziqiang; Castillo-Ramirez, Santiago; Córdoba-Castro, Luz América; López-Lara, Isabel M; Geiger, Otto; Sohlenkamp, Christian; Christopher Fenno, J

    2017-03-01

    Treponema denticola synthesizes phosphatidylcholine through a licCA-dependent CDP-choline pathway identified only in the genus Treponema. However, the mechanism of conversion of CDP-choline to phosphatidylcholine remained unclear. We report here characterization of TDE0021 (herein designated cpt) encoding a 1,2-diacylglycerol choline phosphotransferase homologous to choline phosphotransferases that catalyze the final step of the highly conserved Kennedy pathway for phosphatidylcholine synthesis in eukaryotes. T. denticola Cpt catalyzed in vitro phosphatidylcholine formation from CDP-choline and diacylglycerol, and full activity required divalent manganese. Allelic replacement mutagenesis of cpt in T. denticola resulted in abrogation of phosphatidylcholine synthesis. T. denticola Cpt complemented a Saccharomyces cerevisiae CPT1 mutant, and expression of the entire T. denticola LicCA-Cpt pathway in E. coli resulted in phosphatidylcholine biosynthesis. Our findings show that T. denticola possesses a unique phosphatidylcholine synthesis pathway combining conserved prokaryotic choline kinase and CTP:phosphocholine cytidylyltransferase activities with a 1,2-diacylglycerol choline phosphotransferase that is common in eukaryotes. Other than in a subset of mammalian host-associated Treponema that includes T. pallidum, this pathway is found in neither bacteria nor Archaea. Molecular dating analysis of the Cpt gene family suggests that a horizontal gene transfer event introduced this gene into an ancestral Treponema well after its divergence from other spirochetes. © 2016 John Wiley & Sons Ltd.

  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. 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

  7. Methionine- and choline-deficient diet induces hepatic changes characteristic of non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Éder Marcolin

    2011-03-01

    Full Text Available CONTEXT: Non-alcoholic steatohepatitis is a disease with a high incidence, difficult diagnosis, and as yet no effective treatment. So, the use of experimental models for non-alcoholic steatohepatitis induction and the study of its routes of development have been studied. OBJECTIVES: This study was designed to develop an experimental model of non-alcoholic steatohepatitis based on a methionine- and choline-deficient diet that is manufactured in Brazil so as to evaluate the liver alterations resulting from the disorder. METHODS: Thirty male C57BL6 mice divided in two groups (n = 15 were used: the experimental group fed a methionine- and choline-deficient diet manufactured by Brazilian company PragSoluções®, and the control group fed a normal diet, for a period of 2 weeks. The animals were then killed by exsanguination to sample blood for systemic biochemical analyses, and subsequently submitted to laparotomy with total hepatectomy and preparation of the material for histological analysis. The statistical analysis was done using the Student's t-test for independent samples, with significance level of 5%. RESULTS: The mice that received the methionine- and choline-deficient diet showed weight loss and significant increase in hepatic damage enzymes, as well as decreased systemic levels of glycemia, triglycerides, total cholesterol, HDL and VLDL. The diagnosis of non-alcoholic steatohepatitis was performed in 100% of the mice that were fed the methionine- and choline-deficient diet. All non-alcoholic steatohepatitis animals showed some degree of macrovesicular steatosis, ballooning, and inflammatory process. None of the animals which were fed the control diet presented histological alterations. All non-alcoholic steatohepatitis animals showed significantly increased lipoperoxidation and antioxidant enzyme GSH activity. CONCLUSION: The low cost and easily accessible methionine- and choline-deficient diet explored in this study is highly effective in

  8. Heterologous expression and characterization of choline oxidase from the soil bacterium Arthrobacter nicotianae.

    Science.gov (United States)

    Ribitsch, D; Karl, W; Wehrschütz-Sigl, E; Tutz, S; Remler, P; Weber, H J; Gruber, K; Stehr, R; Bessler, C; Hoven, N; Sauter, K; Maurer, K H; Schwab, H

    2009-01-01

    In the course of a microbial screening of soil samples for new oxidases, different enrichment strategies were carried out. With choline as the only carbon source, a microorganism was isolated and identified as Arthrobacter nicotianae. From this strain, a gene coding for a choline oxidase was isolated from chromosomal DNA. This gene named codA was cloned in Escherichia coli BL21-Gold and the protein (An_CodA) heterologously overexpressed as a soluble intracellular protein of 59.1 kDa. Basic biochemical characterization of purified protein revealed a pH optimum of 7.4 and activity over a broad temperature range (15-70 degrees C). Specific activities were determined toward choline chloride (4.70 +/- 0.12 U/mg) and the synthetic analogs bis(2-hydroxyethyl)-dimethylammonium chloride (0.05 +/- 0.45 x 10(-2) U/mg) and tris-(2-hydroxyethyl)-methylammonium methylsulfate (0.01 +/- 0.12 x 10(-2) U/mg). With increasing number of oxidizable groups, a significant decrease in activity was noted. Determination of kinetic parameters in atmorspheric oxygen resulted in K (M) = 1.51 +/- 0.09 mM and V (max) = 42.73 +/- 0.42 mU/min for choline chloride and K (M) = 4.77 +/- 0.76 mM and V (max) = 48.40 +/- 2.88 mU/min for the reaction intermediate betaine aldehyde respectively. Nuclear magnetic resonance spectroscopic analysis of the products formed during the enzyme reaction with choline chloride showed that in vitro the intermediate betaine aldehyde exists also free in solution.

  9. Choline intake during pregnancy and child cognition at age 7 years.

    Science.gov (United States)

    Boeke, Caroline E; Gillman, Matthew W; Hughes, Michael D; Rifas-Shiman, Sheryl L; Villamor, Eduardo; Oken, Emily

    2013-06-15

    Animal models indicate that exposure to choline in utero improves visual memory through cholinergic transmission and/or epigenetic mechanisms. Among 895 mothers in Project Viva (eastern Massachusetts, 1999-2002 to 2008-2011), we estimated the associations between intakes of choline, vitamin B12, betaine, and folate during the first and second trimesters of pregnancy and offspring visual memory (measured by the Wide Range Assessment of Memory and Learning, Second Edition (WRAML2), Design and Picture Memory subtests) and intelligence (measured using the Kaufman Brief Intelligence Test, Second Edition (KBIT-2)) at age 7 years. Mean second-trimester intakes were 328 (standard deviation (SD), 63) mg/day for choline, 10.5 (SD, 5.1) µg/day for vitamin B12, 240 (SD, 104) mg/day for betaine, and 1,268 (SD, 381) µg/day for folate. Mean age 7 test scores were 17.2 (SD, 4.4) points on the WRAML 2 Design and Picture Memory subtests, 114.3 (SD, 13.9) points on the verbal KBIT-2, and 107.8 (SD, 16.5) points on the nonverbal KBIT-2. In a model adjusting for maternal characteristics, the other nutrients, and child's age and sex, the top quartile of second-trimester choline intake was associated with a child WRAML2 score 1.4 points higher (95% confidence interval: 0.5, 2.4) than the bottom quartile (P-trend = 0.003). Results for first-trimester intake were in the same direction but weaker. Intake of the other nutrients was not associated with the cognitive tests administered. Higher gestational choline intake was associated with modestly better child visual memory at age 7 years.

  10. Protective potential of Emblica Officinalis Linn. against radiation and lead induced hepatic lesion in Swiss albino mice

    International Nuclear Information System (INIS)

    Purohit, R.K.; Bhartiya, K.M.; Isran, Rakesh; Bhati, Sharwan; Pyarelal; Basu, Arindam

    2013-01-01

    Exposure of living systems to ionizing radiation causes a variety of damages to DNA and membranes due to generation of free radicals and reactive oxygen species. So there is a need of hour is to search for an ideal radioprotector which could minimize the deleterious and damaging effects caused by ionizing radiation. Radioprotectors are agents which reduce the radiation effects on cell when applied prior to exposure of radiation. The aim of this study was to access the efficacy of Emblica officinalis in reducing radiation and lead induced changes in mice liver. For the present experiment, healthy male Swiss albino mice (6-8 weeks) were selected and maintained under standard conditions of temperature and light. Fruit extract of Emblica was fed orally at the dose of 0.01 ml/animal/day.The animal were divided into seven groups according to the treatment i.e. lead acetate solution as drinking water (group-II) or exposed to 3.5 or 7.0 Gy gamma radiation (group-III) or combined treatment of radiation and lead acetate (group-IV). The animals of experimental groups were administered Emblica extract seven days prior to radiation or lead acetate treatment (group V, VI and VII) respectively. The animals from all the groups were sacrificed by cervical dislocation at each post-treatment intervals of 1, 2, 4, 7, 14 and 28 days. After sacrificing the animals pieces of liver were taken out and some of them were kept at -20℃ for different biochemical parameters. The histopathological changes included cytoplasmic degranulation, vacuolation, hyperaemia, pycnotic and crenated nuclei. The changes observed in the control groups were compared with the respective experimental groups. An increase in the value of total proteins, glycogen, acid phosphatase, alkaline phosphatase activity and RNA was observed up to day - 14 in the non drug treated group and day 7 in the Emblica treated groups, thereafter value declined up to day - 28 without reaching to normal. Whereas the value of

  11. Protective and ameliorative effect of sea buckthorn leaf extract supplementation on lead induced hemato-biochemical alterations in Wistar rats

    Directory of Open Access Journals (Sweden)

    Rizwana Zargar

    2016-09-01

    ameliorative group in comparison to lead intoxicated groups. Conclusion: SLE administration at 100 mg/kg b.wt. to lead intoxicated Wistar rats may be used to protect/ameliorate lead induced biochemical alterations in Wistar rats.

  12. 15. Sensitivity in visualizing vegetations in cardiac lead-induced endocarditis: A comparative study between transesophageal vs. transthoracic echocardiography

    Directory of Open Access Journals (Sweden)

    A. AlFagih

    2016-07-01

    Full Text Available Despite advancement in sterile cardiac device implantation techniques, wound infections and/or bacteremia remain a significant problem. The presence of a vegetation in lead-induced endocarditis (LIE is a critical factor that determines the management. Transthoracic (TTE and Transesophageal (TEE Echocardiography are two different cardiac modalities that are used for the detection of lead vegetation. However, it is not yet clear which of the two has the highest diagnostic accuracy. We aim to identify which of the two has the highest sensitivity. In addition, we aim to correlate the existence of a vegetation with blood and wound culture results. We conducted a chart review in 113 patients whom underwent lead extraction at Prince Sultan Cardiac Center in Saudi Arabia during the period of Jan, 2002 to Jul, 2015. Six patients underwent lead extraction twice, increasing the number to be a total of 119 cases. Out of the study cohort, we include 38 patients who had both TTE and TEE done prior to lead extraction. Data regarding TTE, TEE, as well as blood and wound cultures were collected from echocardiography and microbiology lab reports using a well-structured case report form.Of the study population, 21 patients (55.3% had lead vegetations visualized either by TTE or TEE. Nineteen patients had vegetations detected by TEE, compared to 6 patients only when TTE was used. The sensitivity of TEE and TTE were 90.5% (CI: 69.6–98.8% and 28.5% (95% CI: 11.3–52.1%, respectively. Blood and wound culture results showed that in the presence of a vegetation, blood cultures were positive in 55% of the cases (P = 0.036 while only 44.4% of those with vegetations had a positive wound culture (P = 0.347. TEE has higher sensitivity in detecting vegetations compared to TTE in LIE. The presence of a vegetation is more likely to be associated with a positive blood culture than a positive wound culture. Further studies ought to measure the accuracy of different

  13. 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.

  14. The utility of 11C-choline PET/CT for imaging prostate cancer: a pictorial guide.

    Science.gov (United States)

    Murphy, Robert C; Kawashima, Akira; Peller, Patrick J

    2011-06-01

    The objective of this article is to provide an illustrative tutorial showing the utility of (11)C-choline PET/CT for imaging prostate cancer. Carbon-11-labeled choline PET/CT is a powerful adjunct to the currently available imaging modalities for evaluating prostate cancer. As with any diagnostic method, false-positives and false-negatives occur. However, these diagnostic errors can be reduced if readers are familiar with the normal and abnormal patterns of (11)C-choline distribution in the body.

  15. 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

  16. Prenatal choline supplementation increases NGF levels in the hippocampus and frontal cortex of young and adult rats.

    Science.gov (United States)

    Sandstrom, Noah J; Loy, Rebekah; Williams, Christina L

    2002-08-23

    Female Sprague-Dawley rats received approximately 300 mg/kg per day of choline chloride through their drinking water on days 11 of pregnancy through birth and the level of nerve growth factor (NGF) in the hippocampus and frontal cortex of their male offspring was measured at 20 and 90 days of age. Prenatal choline supplementation caused significant increases in hippocampal NGF levels at 20 and 90 days of age, while levels of NGF in the frontal cortex were elevated in choline-supplemented rats at 20 days of age, but not 90 days of age. These results suggest that increases in NGF levels during development or adulthood may be one mechanism underlying improvements in spatial and temporal memory of adult rats exposed to elevated levels of choline chloride perinatally.

  17. 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.

  18. Early second trimester maternal plasma choline and betaine are related to measures of early cognitive development in term infants.

    Directory of Open Access Journals (Sweden)

    Brian T F Wu

    Full Text Available The importance of maternal dietary choline for fetal neural development and later cognitive function has been well-documented in experimental studies. Although choline is an essential dietary nutrient for humans, evidence that low maternal choline in pregnancy impacts neurodevelopment in human infants is lacking. We determined potential associations between maternal plasma free choline and its metabolites betaine and dimethylglycine in pregnancy and infant neurodevelopment at 18 months of age.This was a prospective study of healthy pregnant women and their full-term, single birth infants. Maternal blood was collected at 16 and 36 weeks of gestation and infant neurodevelopment was assessed at 18 months of age for 154 mother-infant pairs. Maternal plasma choline, betaine, dimethylglycine, methionine, homocysteine, cysteine, total B12, holotranscobalamin and folate were quantified. Infant neurodevelopment was evaluated using the Bayley Scales of Infant Development-III. Multivariate regression, adjusting for covariates that impact development, was used to determine the associations between maternal plasma choline, betaine and dimethylglycine and infant neurodevelopment.The maternal plasma free choline at 16 and 36 weeks gestation was median (interquartile range 6.70 (5.78-8.03 and 9.40 (8.10-11.3 µmol/L, respectively. Estimated choline intakes were (mean ± SD 383 ± 98.6 mg/day, and lower than the recommended 450 mg/day. Betaine intakes were 142 ± 70.2 mg/day. Significant positive associations were found between infant cognitive test scores and maternal plasma free choline (B=6.054, SE=2.283, p=0.009 and betaine (B=7.350, SE=1.933, p=0.0002 at 16 weeks of gestation. Maternal folate, total B12, or holotranscobalamin were not related to infant development.We show that choline status in the first half of pregnancy is associated with cognitive development among healthy term gestation infants. More work is needed on the potential limitation of choline

  19. Stress-induced stimulation of choline transport in cultured choroid plexus epithelium exposed to low concentrations of cadmium

    Science.gov (United States)

    Young, Robin K.

    2013-01-01

    The choroid plexus epithelium forms the blood-cerebrospinal fluid barrier and accumulates essential minerals and heavy metals. Choroid plexus is cited as being a “sink” for heavy metals and excess minerals, serving to minimize accumulation of these potentially toxic agents in the brain. An understanding of how low doses of contaminant metals might alter transport of other solutes in the choroid plexus is limited. Using primary cultures of epithelial cells isolated from neonatal rat choroid plexus, our objective was to characterize modulation of apical uptake of the model organic cation choline elicited by low concentrations of the contaminant metal cadmium (CdCl2). At 50–1,000 nM, cadmium did not directly decrease or increase 30-min apical uptake of 10 μM [3H]choline. However, extended exposure to 250–500 nM cadmium increased [3H]choline uptake by as much as 75% without marked cytotoxicity. In addition, cadmium induced heat shock protein 70 and heme oxygenase-1 protein expression and markedly induced metallothionein gene expression. The antioxidant N-acetylcysteine attenuated stimulation of choline uptake and induction of stress proteins. Conversely, an inhibitor of glutathione synthesis l-buthionine-sulfoximine (BSO) enhanced stimulation of choline uptake and induction of stress proteins. Cadmium also activated ERK1/2 MAP kinase. The MEK1 inhibitor PD98059 diminished ERK1/2 activation and attenuated stimulation of choline uptake. Furthermore, inhibition of ERK1/2 activation abated stimulation of choline uptake in cells exposed to cadmium with BSO. These data indicate that in the choroid plexus, exposure to low concentrations of cadmium may induce oxidative stress and consequently stimulate apical choline transport through activation of ERK1/2 MAP kinase. PMID:24401988

  20. Potentiation of lead-induced cell death in PC12 cells by glutamate: Protection by N-acetylcysteine amide (NACA), a novel thiol antioxidant

    International Nuclear Information System (INIS)

    Penugonda, Suman; Mare, Suneetha; Lutz, P.; Banks, William A.; Ercal, Nuran

    2006-01-01

    Oxidative stress has been implicated as an important factor in many neurological diseases. Oxidative toxicity in a number of these conditions is induced by excessive glutamate release and subsequent glutamatergic neuronal stimulation. This, in turn, causes increased generation of reactive oxygen species (ROS), oxidative stress, excitotoxicity, and neuronal damage. Recent studies indicate that the glutamatergic neurotransmitter system is involved in lead-induced neurotoxicity. Therefore, this study aimed to (1) investigate the potential effects of glutamate on lead-induced PC12 cell death and (2) elucidate whether the novel thiol antioxidant N-acetylcysteine amide (NACA) had any protective abilities against such cytotoxicity. Our results suggest that glutamate (1 mM) potentiates lead-induced cytotoxicity by increased generation of ROS, decreased proliferation (MTS), decreased glutathione (GSH) levels, and depletion of cellular adenosine-triphosphate (ATP). Consistent with its ability to decrease ATP levels and induce cell death, lead also increased caspase-3 activity, an effect potentiated by glutamate. Exposure to glutamate and lead elevated the cellular malondialdehyde (MDA) levels and phospholipase-A 2 (PLA 2 ) activity and diminished the glutamine synthetase (GS) activity. NACA protected PC12 cells from the cytotoxic effects of glutamate plus lead, as evaluated by MTS assay. NACA reduced the decrease in the cellular ATP levels and restored the intracellular GSH levels. The increased levels of ROS and MDA in glutamate-lead treated cells were significantly decreased by NACA. In conclusion, our data showed that glutamate potentiated the effects of lead-induced PC12 cell death by a mechanism involving mitochondrial dysfunction (ATP depletion) and oxidative stress. NACA had a protective role against the combined toxic effects of glutamate and lead by inhibiting lipid peroxidation and scavenging ROS, thus preserving intracellular GSH

  1. 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.

  2. 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

  3. Daunorubicin and doxorubicin inhibit the [{sup 11}C]choline accumulation in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Mikecz, Pal [Department of Nuclear Medicine, University of Debrecen, Medical and Health Science Centre, 4012 Debrecen, Nagyerdei krt. 98 (Hungary)], E-mail: pal@pet.dote.hu; Marian, Terez; Miklovicz, Tuende; Galuska, Laszlo [Department of Nuclear Medicine, University of Debrecen, Medical and Health Science Centre, 4012 Debrecen, Nagyerdei krt. 98 (Hungary); Krasznai, Zoltan; Toth, Agnes; Goda, Katalin [Department of Biophysics and Cell Biology, University of Debrecen, Medical and Health Science Centre, 4012 Debrecen, Nagyerdei krt. 98 (Hungary); Tron, Lajos [Department of Nuclear Medicine, University of Debrecen, Medical and Health Science Centre, 4012 Debrecen, Nagyerdei krt. 98 (Hungary); Hernadi, Zoltan; Krasznai, Zoard T. [Department of Obstetrics and Gynecology, University of Debrecen, Medical and Health Science Centre, 4012 Debrecen, Nagyerdei krt. 98 (Hungary)

    2009-10-15

    We studied how very short (10-40 min) incubation with anthracycline derivatives modifies the accumulation of PET tumor-diagnostic radiotracers in cancer cells. The human ovarian A2780 and A2780AD, human B lymphoid JY, human epidermoid KB-3-1 and KB-V-1, and smooth muscle DDT1 MF-2 cells were pre-incubated with daunorubicin and doxorubicin, and the uptake of [{sup 18}F]FDG and [{sup 11}C]choline was measured. Anthracycline treatment decreased remarkably the [{sup 11}C]choline accumulation in a concentration dependent manner, while it did not modify significantly the [{sup 18}F]FDG uptake of the cells.

  4. Bacterial use of choline to tolerate salinity shifts in sea-ice brines

    DEFF Research Database (Denmark)

    Firth, E.; Carpenter, S. D.; Sørensen, H. L.

    2016-01-01

    Bacteria within the brine network of sea ice experience temperature-driven fluctuations in salinity on both short and long temporal scales, yet their means of osmoprotection against such fluctuations is poorly understood. One mechanism used to withstand the ion fluxes caused by salinity shifts...... brines drained from sea ice in Kanajorsuit Bay (2013) and Kobbefjord (2014), Greenland, we measured the utilization of 14C-choline (precursor to glycine betaine, a common compatible solute) at -1°C upon salinity shifts to double and to half the starting salinity. In all cases and across a range...... that an abrupt downshift in salinity prompted rapid (subsecond) expulsion of retained 14C-solute, but that uptake of 14C-choline and solute retention resumed when salinity was returned to starting value. Overall, the results indicate that bacteria in sea-ice brines use compatible solutes for osmoprotection...

  5. A selective 15N-to- 1H polarization transfer sequence for more sensitive detection of 15N-choline

    Science.gov (United States)

    Pfeilsticker, Jessica A.; Ollerenshaw, Jason E.; Norton, Valerie A.; Weitekamp, Daniel P.

    2010-07-01

    The sensitivity and information content of heteronuclear nuclear magnetic resonance is frequently optimized by transferring spin order of spectroscopic interest to the isotope of highest detection sensitivity prior to observation. This strategy is extended to 15N-choline using the scalar couplings to transfer polarization from 15N to choline's nine methyl 1H spins in high field. A theoretical analysis of a sequence using nonselective pulses shows that the optimal efficiency of this transfer is decreased by 62% as the result of competing 15N- 1H couplings involving choline's four methylene protons. We have therefore incorporated a frequency-selective pulse to support evolution of only the 15N-methyl 1H coupling during the transfer period. This sequence provides a 52% sensitivity enhancement over the nonselective version in in vitro experiments on a sample of thermally polarized 15N-choline in D 2O. Further, the 15N T1 of choline in D 2O was measured to be 217 ± 38 s, the 15N-methyl 1H coupling constant was found to be 0.817 ± 0.001 Hz, and the larger of choline's two 15N-methylene 1H coupling constants was found to be 3.64 ± 0.01 Hz. Possible improvements and applications to in vivo experiments using long-lived hyperpolarized heteronuclear spin order are discussed.

  6. 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.

  7. Choline supplementation alters some amino acid concentrations with no change in homocysteine in children with cystic fibrosis and pancreatic insufficiency.

    Science.gov (United States)

    Alshaikh, Belal; Schall, Joan I; Maqbool, Asim; Mascarenhas, Maria; Bennett, Michael J; Stallings, Virginia A

    2016-05-01

    The present study determined the plasma amino acid status in children with cystic fibrosis (CF) and pancreatic insufficiency (PI) in the modern medical and nutritional care setting and investigated the effect of choline supplementation on amino acid status. A total of 110 children aged 5 to 18 years with CF and PI were randomized to receive choline-enriched structured lipid (LYM-X-SORB) or placebo with similar energy and fat content. Plasma amino acids were measured at baseline and 3 and 12 months. We hypothesized that choline supplementation would result in lower plasma homocysteine concentrations in children with CF. At baseline, dietary protein intake was high and the amino acid profile was within laboratory reference ranges in most participants. Alanine and cysteine were elevated in 24% and 36% of participants, respectively. Children with baseline alanine above reference range had improved weight, body mass index, and fat-free mass. Low homocysteine was found in 62% of children 11 years and older. After 3 and 12 months, there was no effect of choline supplementation on methionine or homocysteine status. Compared with placebo, choline supplementation resulted in increased glycine and decreased threonine, histidine, valine, and total branch chained amino acids at 12 months. In conclusion, daily choline supplementation with LYM-X-SORB did not alter methionine-homocysteine metabolism but did result in alterations in other amino acids in children with CF and PI. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Choline Supplementation Normalizes Fetal Adiposity and Reduces Lipogenic Gene Expression in a Mouse Model of Maternal Obesity.

    Science.gov (United States)

    Jack-Roberts, Chauntelle; Joselit, Yaelle; Nanobashvili, Khatia; Bretter, Rachel; Malysheva, Olga V; Caudill, Marie A; Saxena, Anjana; Axen, Kathleen; Gomaa, Ahmed; Jiang, Xinyin

    2017-08-18

    Maternal obesity increases fetal adiposity which may adversely affect metabolic health of the offspring. Choline regulates lipid metabolism and thus may influence adiposity. This study investigates the effect of maternal choline supplementation on fetal adiposity in a mouse model of maternal obesity. C57BL/6J mice were fed either a high-fat (HF) diet or a control (NF) diet and received either 25 mM choline supplemented (CS) or control untreated (CO) drinking water for 6 weeks before timed-mating and throughout gestation. At embryonic day 17.5, HF feeding led to higher ( p < 0.05) percent total body fat in fetuses from the HFCO group, while the choline supplemented HFCS group did not show significant difference versus the NFCO group. Similarly, HF feeding led to higher ( p < 0.05) hepatic triglyceride accumulation in the HFCO but not the HFCS fetuses. mRNA levels of lipogenic genes such as Acc1 , Fads1 , and Elovl5 , as well as the transcription factor Srebp1c that favors lipogenesis were downregulated ( p < 0.05) by maternal choline supplementation in the HFCS group, which may serve as a mechanism to reduce fat accumulation in the fetal liver during maternal HF feeding. In summary, maternal choline supplementation improves indices of fetal adiposity in obese dams at late gestation.

  9. Sex-dependent actions of amyloid beta peptides on hippocampal choline carriers of postnatal rats

    Czech Academy of Sciences Publication Activity Database

    Krištofíková, Z.; Říčný, Jan; Kozmiková, I.; Řípová, D.; Zach, P.; Klaschka, Jan

    2006-01-01

    Roč. 31, č. 3 (2006), s. 351-360 ISSN 0364-3190 R&D Projects: GA ČR(CZ) GA305/03/1547 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z10300504 Keywords : amyloid beta peptide * high affinity choline transport * rat hippocampus Subject RIV: ED - Physiology Impact factor: 2.139, year: 2006

  10. Cerebral Acetylcholine and Choline Contents and Turnover Following Low-Dose Acetylcholinesterase Inhibitor Treatment in Rats

    Science.gov (United States)

    2006-05-01

    Accounting Office 2003; McCauley et al. 2001), as well as epidemiological studies (Wolfe et al. 1998). Prophylactic administration of PGW service...Stratton JA (1979) The protection of primates against soman poisoning by pretreatment with pyridostigmine. J Pharm Pharmacol 31: 295-299 Flynn CJ, Wecker...L (1986) Elevated choline levels in brain. A non-cholinergic component of organophosphate toxicity. Biochem.Pharmacol. 35: 3115-3121 Fosbraey P

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Serum betaine but not choline is inversely associated with breast cancer risk: a case-control study in China.

    Science.gov (United States)

    Du, Yu-Feng; Lin, Fang-Yu; Long, Wei-Qing; Luo, Wei-Ping; Yan, Bo; Xu, Ming; Mo, Xiong-Fei; Zhang, Cai-Xia

    2017-04-01

    Choline and betaine are important for DNA methylation and synthesis, and may affect tumor carcinogenesis. To our knowledge, no previous study has examined the association between serum choline and betaine and breast cancer risk. This study aimed to examine whether serum choline and betaine were inversely associated with breast cancer risk among Chinese women. This hospital-based case-control study consecutively recruited 510 breast cancer cases and 518 frequency-matched (age and residence) controls, and blood samples were available for 500 cases and 500 controls. Serum choline and betaine were assayed by high-performance liquid chromatography-tandem mass spectrometry. Multiple unconditional logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs). An inverse association with breast cancer risk was observed for serum betaine (fourth vs first quartile adjusted OR 0.68, 95 % CI 0.47-0.97) and for the ratio of serum betaine to choline (fourth vs first quartile adjusted OR 0.70, 95 % CI 0.48-1.00), but not for serum choline (fourth vs first quartile adjusted OR 0.80, 95 % CI 0.56-1.15). Serum betaine was inversely associated with breast cancer risk in subjects with below-median dietary folate intake (fourth vs first quartile adjusted OR 0.48, 95 % CI 0.30-0.77). This study suggested that serum betaine but not choline was inversely associated with breast cancer risk. This result needed to be further confirmed by the prospective studies.

  16. 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.)

  17. Prenatal choline supplementation alters the timing, emotion, and memory performance (TEMP) of adult male and female rats as indexed by differential reinforcement of low-rate schedule behavior

    OpenAIRE

    Cheng, Ruey-Kuang; MacDonald, Christopher J.; Williams, Christina L.; Meck, Warren H.

    2008-01-01

    Choline availability in the maternal diet has a lasting effect on brain and behavior of the offspring. To further delineate the impact of early nutritional status, we examined effects of prenatal-choline supplementation on timing, emotion, and memory performance of adult male and female rats. Rats that were given sufficient choline (CON: 1.1 g/kg) or supplemental choline (SUP: 5.0 g/kg) during embryonic days (ED) 12–17 were trained with a differential reinforcement of low-rate (DRL) schedule ...

  18. N-Acetyl-L-Cysteine Affords Protection against Lead-Induced Cytotoxicity and Oxidative Stress in Human Liver Carcinoma (HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Paul B. Tchounwou

    2007-06-01

    Full Text Available Although lead exposure has declined in recent years as a result of change to lead-free gasoline, several epidemiological have pointed out that it represents a medical and public health emergency, especially in young children consuming high amounts of lead-contaminated flake paints. A previous study in our laboratory indicated that lead exposure induces cytotoxicity in human liver carcinoma cells. In the present study, we evaluated the role of oxidative stress in lead-induced toxicity, and the protective effect of the anti-oxidant n-acetyl-l-cysteine (NAC. We hypothesized that oxidative stress plays a role in lead-induced cytotoxicity, and that NAC affords protection against this adverse effect. To test this hypothesis, we performed the MTT [3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide] assay and the trypan blue exclusion test for cell viability. We also performed the thiobarbituric acid test for lipid peroxidation. Data obtained from the MTT assay indicated that NAC significantly increased the viability of HepG2 cells in a dosedependent manner upon 48 hours of exposure. Similar trend was obtained with the trypan blue exclusion test. Data generated from the thiobarbituric acid test showed a significant (p ≤ 0.05 increase of MDA levels in lead nitrate-treated HepG2 cells compared to control cells. Interestingly, the addition of NAC to lead nitrate-treated HepG2 cells significantly decreased cellular content of reactive oxygen species (ROS, as evidenced by the decrease in lipid peroxidation byproducts. Overall, findings from this study suggest that NAC inhibits lead nitrate-induced cytotoxicity and oxidative stress in HepG2 cells. Hence, NAC may be used as a salvage therapy for lead-induced toxicity in exposed persons.

  19. Prospective head-to-head comparison of11C-choline-PET/MR and11C-choline-PET/CT for restaging of biochemical recurrent prostate cancer.

    Science.gov (United States)

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

    2017-12-01

    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. 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

  1. Plasma Metabolites From Choline Pathway and Risk of Cardiovascular Disease in the PREDIMED (Prevention With Mediterranean Diet) Study.

    Science.gov (United States)

    Guasch-Ferré, Marta; Hu, Frank B; Ruiz-Canela, Miguel; Bulló, Mònica; Toledo, Estefanía; Wang, Dong D; Corella, Dolores; Gómez-Gracia, Enrique; Fiol, Miquel; Estruch, Ramon; Lapetra, José; Fitó, Montserrat; Arós, Fernando; Serra-Majem, Lluís; Ros, Emilio; Dennis, Courtney; Liang, Liming; Clish, Clary B; Martínez-González, Miguel A; Salas-Salvadó, Jordi

    2017-10-28

    The relationship between plasma concentrations of betaine and choline metabolism and major cardiovascular disease (CVD) end points remains unclear. We have evaluated the association between metabolites from the choline pathway and risk of incident CVD and the potential modifying effect of Mediterranean diet interventions. We designed a case-cohort study nested within the PREDIMED (Prevention With Mediterranean Diet) trial, including 229 incident CVD cases and 751 randomly selected participants at baseline, followed up for 4.8 years. We used liquid chromatography-tandem mass spectrometry to measure, at baseline and at 1 year of follow-up, plasma concentrations of 5 metabolites in the choline pathway: trimethylamine N-oxide, betaine, choline, phosphocholine, and α-glycerophosphocholine. We have calculated a choline metabolite score using a weighted sum of these 5 metabolites. We used weighted Cox regression models to estimate CVD risk. The multivariable hazard ratios (95% confidence intervals) per 1-SD increase in choline and α-glycerophosphocholine metabolites were 1.24 (1.05-1.46) and 1.24 (1.03-1.50), respectively. The baseline betaine/choline ratio was inversely associated with CVD. The baseline choline metabolite score was associated with a 2.21-fold higher risk of CVD across extreme quartiles (95% confidence interval, 1.36-3.59; P <0.001 for trend) and a 2.27-fold higher risk of stroke (95% confidence interval, 1.24-4.16; P <0.001 for trend). Participants in the higher quartiles of the score who were randomly assigned to the control group had a higher risk of CVD compared with participants in the lower quartile and assigned to the Mediterranean diet groups ( P =0.05 for interaction). No significant associations were observed for 1-year changes in individual plasma metabolites and CVD. A metabolite score combining plasma metabolites from the choline pathway was associated with an increased risk of CVD in a Mediterranean population at high cardiovascular risk

  2. Managing Reverse Logistics or Reversing Logistics Management?

    NARCIS (Netherlands)

    M.P. de Brito (Marisa)

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse

  3. Automated evaluation of protein binding affinity of anti-inflammatory choline based ionic liquids.

    Science.gov (United States)

    Ribeiro, Rosa; Pinto, Paula C A G; Azevedo, Ana M O; Bica, Katharina; Ressmann, Anna K; Reis, Salette; Saraiva, M Lúcia M F S

    2016-04-01

    In this work, an automated system for the study of the interaction of drugs with human serum albumin (HSA) was developed. The methodology was based on the quenching of the intrinsic fluorescence of HSA by binding of the drug to one of its binding sites. The fluorescence quenching assay was implemented in a sequential injection analysis (SIA) system and the optimized assay was applied to ionic liquids based on the association of non-steroidal anti-inflammatory drugs with choline (IL-API). In each cycle, 100 µL of HSA and 100 µL of IL-API (variable concentration) were aspirated at a flow rate of 1 mL min(-1) and then sent through the reaction coil to the detector where the fluorescence intensity was measured. In the optimized conditions the effect of increasing concentrations of choline ketoprofenate and choline naproxenate (and respective starting materials: ketoprofen and naproxen) on the intrinsic fluorescence of HSA was studied and the dissociation constants (Kd) were calculated by means of models of drug-protein binding in the equilibrium. The calculated Kd showed that all the compounds bind strongly to HSA (Kd<100 µmol L(-1)) and that the use of the drugs in the IL format does not affect or can even improve their HSA binding. The obtained results were compared with those provided by a conventional batch assay and the relative errors were lower than 4.5%. The developed SIA methodology showed to be robust and exhibited good repeatability in all the assay conditions (rsd<6.5%). Copyright © 2015 Elsevier B.V. All rights reserved.

  4. 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

  5. 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.

  6. HIV-1 reverse transcription.

    Science.gov (United States)

    Hu, Wei-Shau; Hughes, Stephen H

    2012-10-01

    Reverse transcription and integration are the defining features of the Retroviridae; the common name "retrovirus" derives from the fact that these viruses use a virally encoded enzyme, reverse transcriptase (RT), to convert their RNA genomes into DNA. Reverse transcription is an essential step in retroviral replication. This article presents an overview of reverse transcription, briefly describes the structure and function of RT, provides an introduction to some of the cellular and viral factors that can affect reverse transcription, and discusses fidelity and recombination, two processes in which reverse transcription plays an important role. In keeping with the theme of the collection, the emphasis is on HIV-1 and HIV-1 RT.

  7. 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.)

  8. 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.

  9. Whole-body diffusion-weighted magnetic resonance imaging (WB-DW-MRI) vs choline-positron emission tomography-computed tomography (choline-PET/CT) for selecting treatments in recurrent prostate cancer.

    Science.gov (United States)

    Conde-Moreno, A J; Herrando-Parreño, G; Muelas-Soria, R; Ferrer-Rebolleda, J; Broseta-Torres, R; Cozar-Santiago, M P; García-Piñón, F; Ferrer-Albiach, C

    2017-05-01

    To determine the effectiveness of whole-body diffusion-weighted magnetic resonance imaging (WB-DW-MRI) in detecting metastases by comparing the results with those from choline-positron emission tomography-computed tomography (choline-PET/CT) in patients with biochemical relapse after primary treatment, and no metastases in bone scintigraphy, CT and/or pelvic MRI, or metastatic/oligometastatic prostate cancer (PCa). Patients with this disease profile who could benefit from treatment with stereotactic body radiation therapy (SBRT) were selected and their responses to these techniques were rated. This was a prospective, controlled, unicentric study, involving 46 consecutive patients from our centre who presented biochemical relapse after adjuvant, salvage or radical treatment with external beam radiotherapy, or brachytherapy. After initial tests (bone scintigraphy, CT, pelvic MRI), 35 patients with oligometastases or without them were selected. 11 patients with multiple metastases were excluded from the study. WB-DW-MRI and choline-PET/CT was then performed on each patient within 1 week. The results were interpreted by specialists in nuclear medicine and MRI. If they were candidates for treatment with ablative SBRT (SABR), they were then evaluated every three months with both tests. Choline-PET/CT detected lesions in 16 patients that were not observable using WB-DW-MRI. The results were consistent in seven patients and in three cases, a lesion was observed using WB-DW-MRI that was not detected with choline-PET/CT. The Kappa value obtained was 0.133 (p = 0.089); the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of WB-DW-MRI were estimated at 44.93, 64.29, 86.11, and 19.15%, respectively. For choline-PET/CT patients, the sensitivity, specificity, PPV, and NPV were 97.10, 58.33, 93.06, and 77.78%, respectively. Choline-PET/CT has a high global sensitivity while WB-DW-MRI has a high specificity, and so they are

  10. 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.)

  11. Choline- versus imidazole-based ionic liquids as functional ingredients in topical delivery systems: cytotoxicity, solubility, and skin permeation studies.

    Science.gov (United States)

    Santos de Almeida, Tânia; Júlio, Ana; Saraiva, Nuno; Fernandes, Ana Sofia; Araújo, Maria Eduarda M; Baby, André Rolim; Rosado, Catarina; Mota, Joana Portugal

    2017-11-01

    Poor drug solubility represents a problem for the development of topical formulations. Since ionic liquids (ILs) can be placed in either lipophilic or hydrophilic solutions, they may be advantageous vehicles in such delivery systems. Nonetheless, it is vital to determine their usefulness when used at concentrations were cell viability is maintained, which was considered herein. Five different ILs were prepared-three imidazole-based ILs: [C2mim][Br], [C4mim][Br], and [C6mim][Br]; and two choline-based ILs: [Cho][Phe] and [Cho][Glu]. Their cytotoxicity in human keratinocytes (HaCat cells), their influence in drug solubility and in percutaneous permeation, using pig skin membranes, was evaluated. Caffeine and salicylic acid were used as model actives. Choline-based ILs proved to be more suitable as functional ingredients, since they showed higher impact on drug solubility and a lower cytotoxicity. The major solubility enhancement was observed for caffeine and further solubility studies were carried out with this active in several concentrations of the choline-based ILs (0.1; 0.2; 0.5; 1.0; 3.0 and 5.0%, w/w) at 25 °C and 32 °C. Solubility was greatly influenced by concentrations up to 0.5%. The choline-based ILs showed no significant impact on the skin permeation, for both actives. The size of the imidazole-based ILs alkyl chain enhances the caffeine solubility and permeation, but also the ILs cytotoxicity. Stable O/W emulsions and gels were prepared containing the less toxic choline-based ILs and caffeine. Our results indicate that the choline-based ILs were effective functional ingredients, since, when used at nontoxic concentrations, they allowed a higher drug loading, while maintaining the stability of the formulations.

  12. Reverse logistics - a framework

    OpenAIRE

    de Brito, M.P.; Dekker, R.

    2002-01-01

    textabstractIn this paper we define and compare Reverse Logistics definitions. We start by giving an understanding framework of Reverse Logistics: the why-what-how. By this means, we put in context the driving forces for Reverse Logistics, a typology of return reasons, a classification of products, processes and actors. In addition we provide a decision framework for Reverse Logistics and we present it according to long, medium and short term decisions, i.e. strategic-tactic-operational decis...

  13. HIV-1 Reverse Transcription

    OpenAIRE

    Hu, Wei-Shau; Hughes, Stephen H.

    2012-01-01

    Reverse transcription and integration are the defining features of the Retroviridae; the common name “retrovirus” derives from the fact that these viruses use a virally encoded enzyme, reverse transcriptase (RT), to convert their RNA genomes into DNA. Reverse transcription is an essential step in retroviral replication. This article presents an overview of reverse transcription, briefly describes the structure and function of RT, provides an introduction to some of the cellular and viral fact...

  14. Reverse logistics - a framework

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); R. Dekker (Rommert)

    2002-01-01

    textabstractIn this paper we define and compare Reverse Logistics definitions. We start by giving an understanding framework of Reverse Logistics: the why-what-how. By this means, we put in context the driving forces for Reverse Logistics, a typology of return reasons, a classification of

  15. Identification and determination by fast atom bombardment mass spectrometry of the compatible solute choline-O-sulfate in Limonium species and other halophytes

    International Nuclear Information System (INIS)

    Hanson, A.D.; Gage, D.A.; Michigan State Univ., East Lansing, MI

    1991-01-01

    A sensitive and specific method was developed for determining choline-0-sulfate by fast atom bombardment mass spectrometry, using a deuterium labelled choline-0-sulfate internal standard. This method was used to survey leaves or shoots of 30 native halophytic species from 14 families, collected from temperate and subtropical saline habitats. The cultivated Limonium species were also found to accumulate choline-0-sulfate when salinised with NaCl or with NaCl plus Na 2 SO 4 under controlled environmental conditions. The identity of choline-0-sulfate in Limonium species was confirmed by high resolution and tandem mass spectrometry, by 1 H nuclear magnetic resonance, and by analysis of hydrolysis products. Tests with Limonium leaf disks showed that the salt glands of this genus secrete very little sulfate. Possible roles for choline-0-sulfate in osmotic adjustment and sulfate detoxification are discussed. 30 refs., 2 tab., 4 figs

  16. 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

  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. 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.

  19. 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.

  20. Choline acetyltransferase in the hippocampus is associated with learning strategy preference in adult male rats.

    Science.gov (United States)

    Hawley, Wayne R; Witty, Christine F; Daniel, Jill M; Dohanich, Gary P

    2015-08-01

    One principle of the multiple memory systems hypothesis posits that the hippocampus-based and striatum-based memory systems compete for control over learning. Consistent with this notion, previous research indicates that the cholinergic system of the hippocampus plays a role in modulating the preference for a hippocampus-based place learning strategy over a striatum-based stimulus--response learning strategy. Interestingly, in the hippocampus, greater activity and higher protein levels of choline acetyltransferase (ChAT), the enzyme that synthesizes acetylcholine, are associated with better performance on hippocampus-based learning and memory tasks. With this in mind, the primary aim of the current study was to determine if higher levels of ChAT and the high-affinity choline uptake transporter (CHT) in the hippocampus were associated with a preference for a hippocampus-based place learning strategy on a task that also could be solved by relying on a striatum-based stimulus--response learning strategy. Results confirmed that levels of ChAT in the dorsal region of the hippocampus were associated with a preference for a place learning strategy on a water maze task that could also be solved by adopting a stimulus-response learning strategy. Consistent with previous studies, the current results support the hypothesis that the cholinergic system of the hippocampus plays a role in balancing competition between memory systems that modulate learning strategy preference. Copyright © 2015 Elsevier B.V. All rights reserved.

  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. Environmentally friendly and non-polluting solvent pretreatment of palm samples for polyphenol analysis using choline chloride deep eutectic solvents.

    Science.gov (United States)

    Fu, Najing; Lv, Runqiu; Guo, Zhixin; Guo, Yiwei; You, Xiaoyu; Tang, Baokun; Han, Dandan; Yan, Hongyuan; Row, Kyung Ho

    2017-04-07

    In this work, choline chloride (ChCl) deep eutectic solvents (DESs) were evaluated for the pretreatment of palm samples in the analysis of polyphenols, such as protocatechuic acid, catechins, epicatechin, and caffeic acid. During the enrichment step of the pretreatment, eight DESs comprising ChCl with ethylene glycol (EG), glycerol (Gly), xylitol (Xyl), phenol (Ph), formic acid (FA), citric acid (CiA), oxalic acid (OA), or malonic acid (MA), were prepared and applied to the reflux extraction of polyphenols from palm samples. All the DESs exhibited higher polyphenol extraction efficiency than methanol, and the highest extraction efficiency was obtained using ChCl-FA (1:1, mole ratio). For the purification step of the pretreatment, eight ChCl DES-modified adsorbents were prepared by hydrothermal polymerization and packed into solid-phase extraction (SPE) cartridges, and ChCl-Urea, ChCl-Gly, ChCl-FA, and water, were used as eluents. The ChCl DES-modified adsorbents were characterized by Fourier transform infrared spectroscopy, thermal gravimetric analysis, scanning electron microscopy, and Brunauer-Emmett-Teller surface analysis, and the polyphenols were analyzed by mass spectrometry and high-performance liquid chromatograph-ultraviolet detection. The highest purification efficiency was obtained using the ChCl-Ph DES-modified adsorbent as the SPE packing material and ChCl-Urea-H 2 O (1:1:5, mole ratio), ChCl-Gly (1:1, mole ratio), ChCl-FA-H 2 O (1:1:5, mole ratio), and H 2 O as the eluents. Compared to conventional purification processes that employ commercial C 18 or C 8 SPE columns with organic solvents as eluents, the ChCl DES-based SPE purification process successfully avoided the use of expensive commercial SPE columns and organic solvents. Furthermore, it isolated a larger amount of the target compounds under the same experimental conditions, and could be applied over five cycles with good reversibility. This work indicates that DESs as green solvents have great

  3. Reversible flowchart languages and the structured reversible program theorem

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2008-01-01

    operators. Reversible flowcharts are r- Turing-complete, meaning that they can simuluate reversible Turing machines without garbage data. We also demonstrate the injectivization of classical flowcharts into reversible flowcharts. The reversible flowchart computation model provides a theoretical...

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  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. 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.

  11. 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.)

  12. Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity.

    Science.gov (United States)

    Nam, Juha; Greenwald, Esther; Jack-Roberts, Chauntelle; Ajeeb, Tamara T; Malysheva, Olga V; Caudill, Marie A; Axen, Kathleen; Saxena, Anjana; Semernina, Ekaterina; Nanobashvili, Khatia; Jiang, Xinyin

    2017-11-01

    Maternal obesity increases placental transport of macronutrients, resulting in fetal overgrowth and obesity later in life. Choline participates in fatty acid metabolism, serves as a methyl donor and influences growth signaling, which may modify placental macronutrient homeostasis and affect fetal growth. Using a mouse model of maternal obesity, we assessed the effect of maternal choline supplementation on preventing fetal overgrowth and restoring placental macronutrient homeostasis. C57BL/6J mice were fed either a high-fat (HF, 60% kcal from fat) diet or a normal (NF, 10% kcal from fat) diet with a drinking supply of either 25 mM choline chloride or control purified water, respectively, beginning 4 weeks prior to mating until gestational day 12.5. Fetal and placental weight, metabolites and gene expression were measured. HF feeding significantly (P<.05) increased placental and fetal weight in the HF-control (HFCO) versus NF-control (NFCO) animals, whereas the HF choline-supplemented (HFCS) group effectively normalized placental and fetal weight to the levels of the NFCO group. Compared to HFCO, the HFCS group had lower (P<.05) glucose transporter 1 and fatty acid transport protein 1 expression as well as lower accumulation of glycogen in the placenta. The HFCS group also had lower (P<.05) placental 4E-binding protein 1 and ribosomal protein s6 phosphorylation, which are indicators of mechanistic target of rapamycin complex 1 activation favoring macronutrient anabolism. In summary, our results suggest that maternal choline supplementation prevented fetal overgrowth in obese mice at midgestation and improved biomarkers of placental macronutrient homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Introduction to reversible computing

    CERN Document Server

    Perumalla, Kalyan S

    2013-01-01

    Few books comprehensively cover the software and programming aspects of reversible computing. Filling this gap, Introduction to Reversible Computing offers an expanded view of the field that includes the traditional energy-motivated hardware viewpoint as well as the emerging application-motivated software approach. Collecting scattered knowledge into one coherent account, the book provides a compendium of both classical and recently developed results on reversible computing. It explores up-and-coming theories, techniques, and tools for the application of rever

  14. 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.

  15. 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

  16. Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease

    Science.gov (United States)

    Bertoia, Monica L.; Pai, Jennifer K.; Cooke, John P.; Joosten, Michel M.; Mittleman, Murray A.; Rimm, Eric B.; Mukamal, Kenneth J.

    2014-01-01

    Objective Few studies have examined the roles of homocysteine and related nutrients in the development of peripheral artery disease (PAD). We examined the associations between plasma homocysteine, dietary B vitamins, betaine, choline, and supplemental folic acid use and incidence of PAD. Methods We used two cohort studies of 72,348 women in the Nurses' Health Study (NHS, 1990-2010) and 44,504 men in the Health Professionals Follow-up Study (HPFS, 1986-2010). We measured plasma homocysteine in nested matched case-control studies of clinically recognized PAD within both cohorts, including 143 PAD cases and 424 controls within the NHS (1990-2010) and 143 PAD cases and 428 controls within the HPFS (1994-2008). We examined the association between diet and risk of incident PAD in the cohorts using a food frequency questionnaire and 790 cases of PAD over 3.1 million person-years of follow-up. Results Higher homocysteine levels were positively associated with risk of PAD in men (adjusted IRR 2.17; 95% CI, 1.08-4.38 for tertile 3 vs. 1). There was no evidence of an association in women (adjusted IRR 1.14; 95% CI, 0.61-2.12). Similarly, higher folate intake, including supplements, was inversely associated with risk of PAD in men (adjusted HR 0.90; 95% CI, 0.82-0.98 for each 250 μg increase) but not women (HR 1.01, 95% CI, 0.88-1.15). Intakes of the other B vitamins, betaine, and choline were not consistently associated with risk of PAD in men or women. Conclusion Homocysteine levels were positively associated and dietary folate intake was inversely associated with risk of PAD in men but not in women. PMID:24819748

  17. The interaction of standard oxime reactivators with hemicholinium-3 sensitive choline carriers.

    Science.gov (United States)

    Soukup, O; Kristofikova, Z; Jun, D; Tambor, V; Ripova, D; Kuca, K

    2012-08-03

    Organophosphorus poisoning manifests as a cholinergic syndrome due to an inhibition of acetylcholinesterase. It is treated symptomatically by anticholinergics and oxime reactivators are used as causal antidotes. Reactivators possess a complex mechanism of action and interact at various levels of the cholinergic transmission. The aim of this study was to investigate the effect of standard oxime reactivators (HI-6, obidoxime, trimedoxime, methoxime and pralidoxime) on the hemicholinium-3 sensitive carriers, which are involved in the high-affinity choline uptake (HACU) transport, a key regulatory step in the synthesis of acetylcholine. The activity of the carriers was estimated in vitro on hippocampal synaptosomes using the substrate (3H)-choline and the competitive inhibitor (3H)-hemicholinium-3. Furthermore, the effect of the reactivators on the fluidity of hippocampal membranes was assessed. All tested compounds, except methoxime, showed an acute inhibitory effect on the carriers, however, only at μM concentrations. Trimedoxime showed the highest potency to inhibit HACU among all tested compounds (I(max) 62%, IC(50)=3 μM). All compounds, except HI-6, influenced also a membrane fluidity in the region of the hydrophilic heads of phospholipid bilayer, nevertheless, only methoxime was able to penetrate more deeply into the hydrocarbon core. We suggest that the direct interaction of oxime reactivators with the carrier protein (HI-6 and trimedoxime) and/or the changes in carrier conformation mediated by alterations in membrane fluidity (trimedoxime, obidoxime and pralidoxime) could occur here. The influence of reactivators on the carriers could be unfavorable in the case of their prolonged administration in vivo. From this point of view, the application of methoxime appears to be the best. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Cerebral acetylcholine and choline contents and turnover following low-dose acetylcholinesterase inhibitors treatment in rats.

    Science.gov (United States)

    Shih, Tsung-Ming; Scremin, Oscar U; Roch, Margareth; Huynh, Ly; Sun, Wei; Jenden, Donald J

    2006-11-01

    Male Sprague-Dawley rats were treated for 3 weeks with (1) regular tap drinking water plus subcutaneous (s.c.) saline (0.5 ml/kg) injections three times/week, (2) pyridostigmine bromide (PB) in drinking water (80 mg/L) plus s.c. saline injections three times/week, (3) regular tap drinking water plus s.c. sarin (0.5 x LD(50)) injections three times/week, or (4) PB in drinking water plus s.c. sarin injections three times/week. Repeated doses of sarin, in the presence or absence of PB, were devoid of acute toxicity during the three-week treatment period. Two, 4, and 16 weeks post-treatment, animals were given an intravenous pulse injection of choline labeled with 4 deuterium atoms (D4Ch) followed, after 1 min, by microwave fixation of the brain in vivo. Tissue levels of endogenous acetylcholine (D0ACh), endogenous choline (D0Ch), D4Ch, and ACh synthesized from D4Ch (D4ACh) were measured by gas-chromatography mass-spectrometry in hippocampus, infundibulum, mesencephalon, neocortex, piriform cortex, and striatum. Ch uptake from blood and ACh turnover were estimated from D4Ch and D4ACh concentrations in brain tissue, respectively. Statistically significant differences among brain regions were found for D0Ch, D4Ch, D0ACh and D4ACh at 2, 4 and 16 weeks post-treatment. However, differences in the values of these parameters between control and drug treatments were found only for D0ACh and D0Ch at 2 and 4 weeks, but not at 16 weeks post-treatment. In conclusion, the results from these experiments do not support a delayed or persistent alteration in cholinergic function after exposure to low doses of PB and/or sarin.

  19. [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

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

    Energy Technology Data Exchange (ETDEWEB)

    Giovacchini, Giampiero [Stadtspital Triemli, Department of Radiology and Nuclear Medicine, Zurich (Switzerland); Incerti, Elena; Mapelli, Paola; Gianolli, Luigi; Picchio, Maria [IRCCS San Raffaele Scientific Institute, Department of Nuclear Medicine, Milano (Italy); Kirienko, Margarita [University of Milano-Bicocca, Milano (Italy); Briganti, Alberto; Gandaglia, Giorgio; Montorsi, Francesco [IRCCS San Raffaele Scientific Institute, Department of Urology, Milano (Italy)

    2015-05-01

    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 [{sup 11}C]choline PET/CT-positive findings and lack of survival analysis. The aim of this study was to assess whether [{sup 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 [{sup 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). [{sup 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 [{sup 11}C]choline PET/CT. Median survival was not achieved in patients with negative [{sup 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 [{sup 11}C]choline PET/CT and 95.5 % (95 % CI 93.5 - 97.5 %) in patients with negative [{sup 11}C]choline PET/CT. In multivariate analysis, [{sup 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 [{sup 11}C]choline PET/CT after biochemical failure

  1. 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

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

    Science.gov (United States)

    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

    2017-01-01

    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

  3. In Vivo 18 FDG/18 Choline Mediated Cerenkov Radiation Energy Transfer (CRET) Multiplexed Optical Imaging for Human Prostate Carcinoma Detection and Staging

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-13-1-0138 TITLE: In Vivo 18-FDG/18-Choline-Mediated Cerenkov Radiation Energy Transfer (CRET) Multiplexed Optical...18-Choline-Mediated Cerenkov Radiation Energy Transfer (CRET) Multiplexed Optical Imaging for Human Prostate Carcinoma Detection and Staging 5b...fluorocholine/18F-FDG Cerenkov radiation energy transfer (CRET) coupled with TF- and ErbB2/3- molecularly targeted near- infrared (NIR) QDs can be used

  4. An algebra of reversible computation.

    Science.gov (United States)

    Wang, Yong

    2016-01-01

    We design an axiomatization for reversible computation called reversible ACP (RACP). It has four extendible modules: basic reversible processes algebra, algebra of reversible communicating processes, recursion and abstraction. Just like process algebra ACP in classical computing, RACP can be treated as an axiomatization foundation for reversible computation.

  5. Tubal Ligation Reversal

    Science.gov (United States)

    ... and other factors. Success rates may be as high as 80 percent or as low as near 40 percent depending on your circumstances. Tubal ligation reversal is abdominal surgery, which carries a risk of infection, bleeding and ...

  6. 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.)

  7. 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

  8. Human TMEM30a Promotes Uptake of Anti-tumor and Bioactive Choline Phospholipids into Mammalian Cells1

    OpenAIRE

    Chen, Rui; Brady, Erin; McIntyre, Thomas M.

    2011-01-01

    Anti-tumor alkylphospholipids initiate apoptosis in transformed HL-60 and Jurkat cells while sparing their progenitors. Edelfosine like other short-chained phospholipids—inflammatory Platelet-activating Factor (PAF) and apoptotic oxidatively-truncated phospholipids—are proposed to have intracellular sites of action, yet a conduit for these choline phospholipids into mammalian cells is undefined. Edelfosine is also accumulated by Saccharomyces cerevisiae in process requiring the membrane prote...

  9. CHKA and PCYT1A gene polymorphisms, choline intake and spina bifida risk in a California population

    Directory of Open Access Journals (Sweden)

    Lammer Edward J

    2006-12-01

    Full Text Available Abstract Background Neural tube defects (NTDs are among the most common of all human congenital defects. Over the last two decades, accumulating evidence has made it clear that periconceptional intake of folic acid can significantly reduce the risk of NTD affected pregnancies. This beneficial effect may be related to the ability of folates to donate methyl groups for critical physiological reactions. Choline is an essential nutrient and it is also a methyl donor critical for the maintenance of cell membrane integrity and methyl metabolism. Perturbations in choline metabolism in vitro have been shown to induce NTDs in mouse embryos. Methods This study investigated whether single nucleotide polymorphisms (SNPs in human choline kinase A (CHKA gene and CTP:phosphocholine cytidylytransferase (PCYT1A gene were risk factors for spina bifida. Fluorescence-based allelic discrimination analysis was performed for the two CHKA intronic SNPs hCV1562388 (rs7928739 and hCV1562393, and PCYT1A SNP rs939883 and rs3772109. The study population consisted of 103 infants with spina bifida and 338 non-malformed control infants who were born in selected California counties in the period 1989–1991. Results The CHKA SNP hCV1562388 genotypes with at least one C allele were associated with a reduced risk of spina bifida (odds ratio = 0.60, 95%CI = 0.38–0.94. The PCYT1A SNP rs939883 genotype AA was associated with a twofold increased risk of spina bifida (odds ratio = 1.89, 95% CI = 0.97–3.67. These gene-only effects were not substantially modified by analytic consideration to maternal periconceptional choline intake. Conclusion Our analyses showed genotype effects of CHKA and PCYT1A genes on spina bifida risk, but did not show evidence of gene-nutrient interactions. The underlying mechanisms are yet to be resolved.

  10. Sex reversal in vertebrates

    OpenAIRE

    2016-01-01

    This special topic issue of Sexual Development gives an overview of sex reversal in vertebrates, from fishes naturally changing their sex, to rodents escaping the mammalian SRY-determining system. It offers eight up-to-date reviews on specific subjects in sex reversal, considering fishes, amphibians, reptiles, birds, marsupials, and placental mammals, including humans. The broad scope of represented animals makes this ideal for students and researchers, especially those interested in the...

  11. 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.

  12. Choline Binding Proteins from Streptococcus pneumoniae: A Dual Role as Enzybiotics and Targets for the Design of New Antimicrobials

    Directory of Open Access Journals (Sweden)

    Beatriz Maestro

    2016-06-01

    Full Text Available Streptococcus pneumoniae (pneumococcus is an important pathogen responsible for acute invasive and non-invasive infections such as meningitis, sepsis and otitis media, being the major cause of community-acquired pneumonia. The fight against pneumococcus is currently hampered both by insufficient vaccine coverage and by rising antimicrobial resistances to traditional antibiotics, making necessary the research on novel targets. Choline binding proteins (CBPs are a family of polypeptides found in pneumococcus and related species, as well as in some of their associated bacteriophages. They are characterized by a structural organization in two modules: a functional module (FM, and a choline-binding module (CBM that anchors the protein to the choline residues present in the cell wall through non-covalent interactions. Pneumococcal CBPs include cell wall hydrolases, adhesins and other virulence factors, all playing relevant physiological roles for bacterial viability and virulence. Moreover, many pneumococcal phages also make use of hydrolytic CBPs to fulfill their infectivity cycle. Consequently, CBPs may play a dual role for the development of novel antipneumococcal drugs, both as targets for inhibitors of their binding to the cell wall and as active cell lytic agents (enzybiotics. In this article, we review the current state of knowledge about host- and phage-encoded pneumococcal CBPs, with a special focus on structural issues, together with their perspectives for effective anti-infectious treatments.

  13. 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.

  14. 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.

  15. What do reversible programs compute?

    DEFF Research Database (Denmark)

    Axelsen, Holger Bock; Glück, Robert

    2011-01-01

    transformation, program transformations such as inversion, and general static prediction of program properties. Historically, work on reversible computing has focussed on reversible simulations of irreversible computations. Here, we take the viewpoint that the property of reversibility itself should...

  16. A silk peptide fraction restores cognitive function in AF64A-induced Alzheimer disease model rats by increasing expression of choline acetyltransferase gene

    International Nuclear Information System (INIS)

    Cha, Yeseul; Lee, Sang Hoon; Jang, Su Kil; Guo, Haiyu; Ban, Young-Hwan; Park, Dongsun; Jang, Gwi Yeong; Yeon, Sungho; Lee, Jeong-Yong; Choi, Ehn-Kyoung; Joo, Seong Soo; Jeong, Heon-Sang; Kim, Yun-Bae

    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.

  17. On thermodynamic and microscopic reversibility

    International Nuclear Information System (INIS)

    Crooks, Gavin E

    2011-01-01

    The word 'reversible' has two (apparently) distinct applications in statistical thermodynamics. A thermodynamically reversible process indicates an experimental protocol for which the entropy change is zero, whereas the principle of microscopic reversibility asserts that the probability of any trajectory of a system through phase space equals that of the time reversed trajectory. However, these two terms are actually synonymous: a thermodynamically reversible process is microscopically reversible, and vice versa

  18. 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.

  19. Choline-induced selective fluorescence quenching of acetylcholinesterase conjugated Au@BSA clusters.

    Science.gov (United States)

    Mathew, Meegle S; Baksi, Ananya; Pradeep, T; Joseph, Kuruvilla

    2016-07-15

    We have developed a highly selective sensitive fluorescent detection of acetylcholine (ACh) using bovine serum albumin (BSA) protected atomically precise clusters of gold. The gold quantum clusters (AuQC@BSA) synthesized using bovine serum albumin and conjugated with acetylcholinesterase (AChE), an enzyme specific for acetylcholine, resulting in AuQC@BSA-AChE. The enzyme, AChE hydrolyzes acetylcholine (ACh) to choline (Ch) which in turn interacts with AuQC@BSA-AChE and quenches its fluorescence, enabling sensing. We have carried out the real time monitoring of the hydrolysis of ACh using electrospray ionization mass spectrometry (ESI MS) to find out the mechanism of fluorescent quenching. The validity of present method for determination of concentration of acetylcholine in real system such as blood was demonstrated. Further, the sensor, AuQC@BSA-AChE can be easily coated on paper and an efficient and cheap sensor can be developed and detection limit for ACh is found to be 10nM. The fluorescent intensity of AuQC@BSA-AChE is sensitive towards acetylcholine in range of 10nM to 6.4µM. This suggests that AuQC@BSA-AChE has an excellent potential to be used for diagnosis of various neuropsychological and neuropsychiatric disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Novel ligands of Choline Acetyltransferase designed by in silico molecular docking, hologram QSAR and lead optimization

    Science.gov (United States)

    Kumar, Rajnish; Långström, Bengt; Darreh-Shori, Taher

    2016-08-01

    Recent reports have brought back the acetylcholine synthesizing enzyme, choline acetyltransferase in the mainstream research in dementia and the cholinergic anti-inflammatory pathway. Here we report, a specific strategy for the design of novel ChAT ligands based on molecular docking, Hologram Quantitative Structure Activity Relationship (HQSAR) and lead optimization. Molecular docking was performed on a series of ChAT inhibitors to decipher the molecular fingerprint of their interaction with the active site of ChAT. Then robust statistical fragment HQSAR models were developed. A library of novel ligands was generated based on the pharmacophoric and shape similarity scoring function, and evaluated in silico for their molecular interactions with ChAT. Ten of the top scoring invented compounds are reported here. We confirmed the activity of α-NETA, the only commercially available ChAT inhibitor, and one of the seed compounds in our model, using a new simple colorimetric ChAT assay (IC50 ~ 88 nM). In contrast, α-NETA exhibited an IC50 of ~30 μM for the ACh-degrading cholinesterases. In conclusion, the overall results may provide useful insight for discovering novel ChAT ligands and potential positron emission tomography tracers as in vivo functional biomarkers of the health of central cholinergic system in neurodegenerative disorders, such as Alzheimer’s disease.

  1. Distinct Localization of Peripheral and Central Types of Choline Acetyltransferase in the Rat Cochlea

    International Nuclear Information System (INIS)

    Kitanishi, Tsuyoshi; Aimi, Yoshinari; Kitano, Hiroya; Suzuki, Mikio; Kimura, Hiroshi; Saito, Atsushi; Shimizu, Takeshi; Tooyama, Ikuo

    2013-01-01

    We previously discovered a splice variant of choline acetyltransferase (ChAT) mRNA, and designated the variant protein pChAT because of its preferential expression in peripheral neuronal structures. In this study, we examined the immunohistochemical localization of pChAT in rat cochlea and compared the distribution pattern to those of common ChAT (cChAT) and acetylcholinesterase. Some neuronal cell bodies and fibers in the spiral ganglia showed immunoreactivity for pChAT, predominantly the small spiral ganglion cells, indicating outer hair cell type II neurons. In contrast, cChAT- and acetylcholinesterase-positive structures were localized to fibers and not apparent in ganglion cells. After ablation of the cochlear nuclei, many pChAT-positive cochlear nerve fibers became clearly visible, whereas fibers immunopositive for cChAT and acetylcholine esterase disappeared. These results suggested that pChAT and cChAT are localized in different systems of the rat cochlea; pChAT in the afferent and cChAT in the efferent structures

  2. Melatonin ameliorates methionine- and choline-deficient diet-induced nonalcoholic steatohepatitis in rats.

    Science.gov (United States)

    Tahan, Veysel; Atug, Ozlen; Akin, Hakan; Eren, Fatih; Tahan, Gulgun; Tarcin, Ozlem; Uzun, Hafize; Ozdogan, Osman; Tarcin, Orhan; Imeryuz, Nese; Ozguner, Fehmi; Celikel, Cigdem; Avsar, Erol; Tozun, Nurdan

    2009-05-01

    Nonalcoholic steatohepatitis (NASH) may progress to advanced fibrosis and cirrhosis. Mainly, oxidative stress and excessive hepatocyte apoptosis are implicated in the pathogenesis of progressive NASH. Melatonin is not only a powerful antioxidant but also an anti-inflammatory and anti-apoptotic agent. We aimed to evaluate the effects of melatonin on methionine- and choline-deficient diet (MCDD)-induced NASH in rats. Thirty-two male Wistar rats were divided into four groups. Two groups were fed with MCDD while the other two groups were fed a control diet, pair-fed. One of the MCDD groups and one of the control diet groups were administered melatonin 50 mg/kg/day intraperitoneally, and the controls were given a vehicle. After 1 month the liver tissue oxidative stress markers, proinflammatory cytokines and hepatocyte apoptosis were studied by commercially available kits. For grading and staging histological lesions, Brunt et al.'s system was used. Melatonin decreased oxidative stress, proinflammatory cytokines and hepatocyte apoptosis. The drug ameliorated the grade of NASH. The present study suggests that melatonin functions as a potent antioxidant, anti-inflammatory and antiapoptotic agent in NASH and may be a therapeutic option.

  3. Comparative assessment of segmentation algorithms for tumor delineation on a test-retest [(11)C]choline dataset.

    Science.gov (United States)

    Tomasi, Giampaolo; Shepherd, Tony; Turkheimer, Federico; Visvikis, Dimitris; Aboagye, Eric

    2012-12-01

    Many methods have been proposed for tumor segmentation from positron emission tomography images. Because of the increasingly important role that [(11)C]choline is playing in oncology and because no study has compared segmentation methods on this tracer, the authors assessed several segmentation algorithms on a [(11)C]choline test-retest dataset. Fixed and adaptive threshold-based methods, fuzzy C-means (FCM), Canny's edge detection method, the watershed transform, and the fuzzy locally adaptive Bayesian algorithm (FLAB) were used. Test-retest [(11)C]choline scans of nine patients with breast cancer were considered and the percent test-retest variability %VAR(TEST-RETEST) of tumor volume (TV) was employed to assess the results. The same methods were then applied to two denoised datasets generated by applying either a Gaussian filter or the wavelet transform. The (semi)automated methods FCM, FLAB, and Canny emerged as the best ones in terms of TV reproducibility. For these methods, the %root mean square error %RMSE of %VAR(TEST-RETEST), defined as %RMSE= variance+mean(2), was in the range 10%-21.2%, depending on the dataset and algorithm. Threshold-based methods gave TV estimates which were extremely variable, particularly on the unsmoothed data; their performance improved on the denoised datasets, whereas smoothing did not have a remarkable impact on the (semi)automated methods. TV variability was comparable to that of SUV(MAX) and SUV(MEAN) (range 14.7%-21.9% for %RMSE of %VAR(TEST-RETEST), after the exclusion of one outlier, 40%-43% when the outlier was included). The TV variability obtained with the best methods was similar to the one reported for TV in previous [(18)F]FDG and [(18)F]FLT studies and to the one of SUV(MAX)∕SUV(MEAN) on the authors' [(11)C]choline dataset. The good reproducibility of [(11)C]choline TV warrants further studies to test whether TV could predict early response to treatment and survival, as for [(18)F]FDG, to complement

  4. 11C-Choline PET/CT in the primary diagnosis of prostate cancer: impact on treatment planning.

    Science.gov (United States)

    Garcia, J R; Jorcano, S; Soler, M; Linero, D; Moragas, M; Riera, E; Miralbell, R; Lomeña, F

    2015-09-01

    Aim of the present study was to evaluate the usefulness of 11C-choline PET/CT for detecting lymphatic or haematogenous spread and for planning radiotherapy in patients with medium-to-high risk prostate cancer. We have included 61 consecutive patients recently diagnosed with cancer prostate by biopsy. All patients were classified as medium-to-high risk: Gleason: 7-9; PSA: 6.3-30.4 ng/mL; stage T2c (N.=20) or stage T3 (N.=41). Image acquisition began 5 min after intravenous injection of 11C-choline (656+119 MBq), starting at the pelvis and continuing craniocaudally. Images were interpreted visually to evaluate uptake by the prostate gland. Lymph nodes with 11C-choline uptake were considered invaded, regardless of their size. Bone lesions were considered positive when they showed greater focal uptake than the surrounding bone. In patients with evidence of lymph-node invasion or bone metastases (15 patients), disease was classified as locoregional, oligometastatic, or multimetastatic. All patients had prostate gland uptake (20 focal, 8 bifocal, and 33 multifocal). Extraprostatic disease was present in 15 patients (24.6%), as follows: 9 (60%) in a single location: in an infradiaphragmatic lymph node (N.=6), in a supradiaphragmatic lymph node (N.=1), and in bone (M1) (N.=2). Six (40%) as multifocal invasion: with both infra- and supradiaphragmatic lymph node involvement (N.=2); with infradiaphragmatic lymph node involvement and M1 bone metastases (N.=3); and infra- and supradiaphragmatic lymph node involvement plus M1 bone metastases (N.=1). Disease was classified as locoregional (N.=6), oligometastatic (N.=5), and multimetastatic (N.=4). The 11 (73.3%) patients with locoregional and oligometastatic disease were selected to undergo intensity-modulated radiation therapy with dose escalation based on the PET findings. Our results suggest that 11C-choline PET/CT is a useful one-stop diagnostic procedure for evaluating patients with medium/high risk prostate cancer scheduled

  5. Reversible Communicating Processes

    Directory of Open Access Journals (Sweden)

    Geoffrey Brown

    2016-02-01

    Full Text Available Reversible distributed programs have the ability to abort unproductive computation paths and backtrack, while unwinding communication that occurred in the aborted paths. While it is natural to assume that reversibility implies full state recovery (as with traditional roll-back recovery protocols, an interesting alternative is to separate backtracking from local state recovery. For example, such a model could be used to create complex transactions out of nested compensable transactions where a programmer-supplied compensation defines the work required to "unwind" a transaction. Reversible distributed computing has received considerable theoretical attention, but little reduction to practice; the few published implementations of languages supporting reversibility depend upon a high degree of central control. The objective of this paper is to demonstrate that a practical reversible distributed language can be efficiently implemented in a fully distributed manner. We discuss such a language, supporting CSP-style synchronous communication, embedded in Scala. While this language provided the motivation for the work described in this paper, our focus is upon the distributed implementation. In particular, we demonstrate that a "high-level" semantic model can be implemented using a simple point-to-point protocol.

  6. Reversed extension flow

    DEFF Research Database (Denmark)

    Nielsen, Jens Kromann; Rasmussen, Henrik K.

    2008-01-01

    Afilament stretching rheometer (FSR) was used for measuring the start-up of uni-axial elongational flow followed by reversed bi-axial flow, both with a constant elongational rate. A narrow molecular mass distribution linear polystyrene with a molecular weight of 145 kg / mole wis subjected...... to the start-up of elongation for three Hencky strain units and subsequently the reversed flow. The integral molecular stress function formulation within the 'interchain pressure' concept agrees with the experiments. In the experiments the Hencky strain at which the str~ss becomes zero (the recovery strain......) in the reversed flow has been identified. The recovery strain is found to increase with elongational rate, and has a maximum value of approximately 1.45. The Doi Edwards model using any stretch evolution equation is not able to predict the correct level of the recovery strain....

  7. Dietary choline and betaine; associations with subclinical markers of cardiovascular disease risk and incidence of CVD, coronary heart disease and stroke: the Jackson Heart Study.

    Science.gov (United States)

    Millard, Heather R; Musani, Solomon K; Dibaba, Daniel T; Talegawkar, Sameera A; Taylor, Herman A; Tucker, Katherine L; Bidulescu, Aurelian

    2018-02-01

    Several mechanisms have been described through which dietary intake of choline and its derivative betaine may be associated in both directions with subclinical atherosclerosis. We assessed the association of dietary intake of choline and betaine with cardiovascular risk and markers of subclinical cardiovascular disease. Data from 3924 Jackson Heart Study (JHS) African-American participants with complete food frequency questionnaire at baseline and follow-up measurements of heart disease measures were used. Multivariable linear regression models were employed to assess associations between choline and betaine intake with carotid intima-media thickness, coronary artery calcium, abdominal aortic calcium and left ventricular mass. Cox proportional hazards regression models were used to estimate associations with time to incident coronary heart disease (CHD), ischemic stroke and cardiovascular disease (CVD). During an average nine years of follow-up, 124 incident CHD events, 75 incident stroke events and 153 incident CVD events were documented. In women, greater choline intake was associated with lower left ventricular mass (p = 0.0006 for trend across choline quartiles) and with abdominal aortic calcium score. Among all JHS participants, there was a statistically significant inverse association between dietary choline intake and incident stroke, β = -0.33 (p = 0.04). Betaine intake was associated with greater risk of incident CHD when comparing the third quartile of intake with the lowest quartile of intake (HR 1.89, 95 % CI 1.14, 3.15). Among our African-American participants, higher dietary choline intake was associated with a lower risk of incident ischemic stroke, and thus putative dietary benefits. Higher dietary betaine intake was associated with a nonlinear higher risk of incident CHD.

  8. Serum Trimethylamine N-oxide, Carnitine, Choline, and Betaine in Relation to Colorectal Cancer Risk in the Alpha Tocopherol, Beta Carotene Cancer Prevention Study.

    Science.gov (United States)

    Guertin, Kristin A; Li, Xinmin S; Graubard, Barry I; Albanes, Demetrius; Weinstein, Stephanie J; Goedert, James J; Wang, Zeneng; Hazen, Stanley L; Sinha, Rashmi

    2017-06-01

    Background: Trimethylamine N-oxide (TMAO), a choline-derived metabolite produced by gut microbiota, and its biomarker precursors have not been adequately evaluated in relation to colorectal cancer risk. Methods: We investigated the relationship between serum concentrations of TMAO and its biomarker precursors (choline, carnitine, and betaine) and incident colorectal cancer risk in a nested case-control study of male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We measured biomarker concentrations in baseline fasting serum samples from 644 incident colorectal cancer cases and 644 controls using LC/MS-MS. Logistic regression models estimated the ORs and 95% confidence interval (CI) for colorectal cancer by quartile (Q) of serum TMAO, choline, carnitine, and betaine concentrations. Results: Men with higher serum choline at ATBC baseline had approximately 3-fold greater risk of developing colorectal cancer over the ensuing (median ± IQR) 14 ± 10 years (in fully adjusted models, Q4 vs. Q1, OR, 3.22; 95% CI, 2.24-4.61; P trend colorectal cancer was similarly robust for proximal, distal, and rectal colon cancers (all P colorectal cancer risk was not statistically significant ( P = 0.25, 0.71, and 0.61, respectively). Conclusions: Higher serum choline concentration (but not TMAO, carnitine, or betaine) was associated with increased risk of colorectal cancer. Impact: Serum choline levels showed strong prognostic value for prediction of incident colorectal cancer risk across all anatomical subsites, suggesting a role of altered choline metabolism in colorectal cancer pathogenesis. Cancer Epidemiol Biomarkers Prev; 26(6); 945-52. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. Maternal choline modifies fetal liver copper, gene expression, DNA methylation, and neonatal growth in the tx-j mouse model of Wilson disease

    Science.gov (United States)

    Medici, Valentina; Shibata, Noreene M; Kharbanda, Kusum K; Islam, Mohammad S; Keen, Carl L; Kim, Kyoungmi; Tillman, Brittany; French, Samuel W; Halsted, Charles H; LaSalle, Janine M

    2014-01-01

    Maternal diet can affect fetal gene expression through epigenetic mechanisms. Wilson disease (WD), which is caused by autosomal recessive mutations in ATP7B encoding a biliary copper transporter, is characterized by excessive hepatic copper accumulation, but variability in disease severity. We tested the hypothesis that gestational supply of dietary methyl groups modifies fetal DNA methylation and expression of genes involved in methionine and lipid metabolism that are impaired prior to hepatic steatosis in the toxic milk (tx-j) mouse model of WD. Female C3H control and tx-j mice were fed control (choline 8 mmol/Kg of diet) or choline-supplemented (choline 36 mmol/Kg of diet) diets for 2 weeks throughout mating and pregnancy to gestation day 17. A second group of C3H females, half of which were used to cross foster tx-j pups, received the same diet treatments that extended during lactation to 21 d postpartum. Compared with C3H, fetal tx-j livers had significantly lower copper concentrations and significantly lower transcript levels of Cyclin D1 and genes related to methionine and lipid metabolism. Maternal choline supplementation prevented the transcriptional deficits in fetal tx-j liver for multiple genes related to cell growth and metabolism. Global DNA methylation was increased by 17% in tx-j fetal livers after maternal choline treatment (P < 0.05). Maternal dietary choline rescued the lower body weight of 21 d tx-j mice. Our results suggest that WD pathogenesis is modified by maternal in utero factors, including dietary choline. PMID:24220304

  10. 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.

  11. Time reversal communication system

    Science.gov (United States)

    Candy, James V.; Meyer, Alan W.

    2008-12-02

    A system of transmitting a signal through a channel medium comprises digitizing the signal, time-reversing the digitized signal, and transmitting the signal through the channel medium. The channel medium may be air, earth, water, tissue, metal, and/or non-metal.

  12. Engineering Encounters: Reverse Engineering

    Science.gov (United States)

    McGowan, Veronica Cassone; Ventura, Marcia; Bell, Philip

    2017-01-01

    This column presents ideas and techniques to enhance your science teaching. This month's issue shares information on how students' everyday experiences can support science learning through engineering design. In this article, the authors outline a reverse-engineering model of instruction and describe one example of how it looked in our fifth-grade…

  13. Sex Reversal in Birds.

    Science.gov (United States)

    Major, Andrew T; Smith, Craig A

    2016-01-01

    Sexual differentiation in birds is controlled genetically as in mammals, although the sex chromosomes are different. Males have a ZZ sex chromosome constitution, while females are ZW. Gene(s) on the sex chromosomes must initiate gonadal sex differentiation during embryonic life, inducing paired testes in ZZ individuals and unilateral ovaries in ZW individuals. The traditional view of avian sexual differentiation aligns with that expounded for other vertebrates; upon sexual differentiation, the gonads secrete sex steroid hormones that masculinise or feminise the rest of the body. However, recent studies on naturally occurring or experimentally induced avian sex reversal suggest a significant role for direct genetic factors, in addition to sex hormones, in regulating sexual differentiation of the soma in birds. This review will provide an overview of sex determination in birds and both naturally and experimentally induced sex reversal, with emphasis on the key role of oestrogen. We then consider how recent studies on sex reversal and gynandromorphic birds (half male:half female) are shaping our understanding of sexual differentiation in avians and in vertebrates more broadly. Current evidence shows that sexual differentiation in birds is a mix of direct genetic and hormonal mechanisms. Perturbation of either of these components may lead to sex reversal. © 2016 S. Karger AG, Basel.

  14. 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.)

  15. Immunohistochemical localization of choline acetyltransferase during development and in Chats mutants of Drosophila melanogaster.

    Science.gov (United States)

    Gorczyca, M G; Hall, J C

    1987-05-01

    The distribution of choline acetyltransferase (CAT) in the nervous system of Drosophila melanogaster was determined by indirect immunohistochemical procedures using a monoclonal antibody specific to the enzyme. Immunoreactivity was first detected in the nervous system of 16 hr embryos, and increased considerably by the end of embryogenesis. Neuropil was preferentially stained, though cell bodies could also be observed. Staining was prominent in the CNS of all 3 larval instars but decreased substantially during the mid-pupal stage. Prior to eclosion, the level of immunoreactivity increased and the adult staining pattern became discernible. In the adult brain, staining was extensive, with numerous structures, such as the optic lobes and mushroom bodies, staining strongly. The adult thoracic ganglia were also moderately immunoreactive. These results imply a wide distribution of cholinergic neurons in the CNS of Drosophila. Immunoreactivity was also determined for 2 temperature-sensitive CAT mutants, Chats1 and Chats2. These files exhibit reduced CAT activity at permissive temperature, 18 degrees C, which eventually falls to undetectable levels after incubation at nonpermissive temperature, 30 degrees C. Chats2 mutants, after incubation at either 18 or 30 degrees C displayed virtually no staining. This result indicated that the immunoreactivity observed in wild-type flies was specifically associated with the enzyme encoded by the Cha gene. The intensity of staining in Chats1 mutants incubated at 18 degrees C appeared greater than in control flies, even though CAT enzyme activity in Chats1 is lower. This suggests that the enzyme molecule itself is structurally altered in Chats1 mutants. After incubation at 30 degrees C, staining in Chats1 flies decreased but did not disappear.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Time-course microarrays reveal early activation of the immune transcriptome in a choline-deficient mouse model of liver injury.

    Science.gov (United States)

    Mitsumoto, Koji; Watanabe, Rina; Nakao, Katsuki; Yonenaka, Hisaki; Hashimoto, Takao; Kato, Norihisa; Kumrungsee, Thanutchaporn; Yanaka, Noriyuki

    2017-09-01

    Choline-deficient diet is extensively used as a model of nonalcoholic fatty liver disease (NAFLD). In this study, we explored genes in the liver for which the expression changed in response to the choline-deficient (CD) diet. Male CD-1 mice were divided into two groups and fed a CD diet with or without 0.2% choline bitartrate for one or three weeks. Hepatic levels of choline metabolites were analyzed by using liquid chromatography mass spectrometry and hepatic gene expression profiles were examined by DNA microarray analysis. The CD diet lowered liver choline metabolites after one week and exacerbated fatty liver between one and three weeks. We identified >300 genes whose expression was significantly altered in the livers of mice after consumption of this CD diet for one week and showed that liver gene expression profiles could be classified into six distinct groups. This study showed that STAT1 and interferon-regulated genes was up-regulated after the CD diet consumption and that the Stat1 mRNA level was negatively correlated with liver phosphatidylcholine level. Stat1 mRNA expression was actually up-regulated in isolated hepatocytes from the mouse liver with the CD diet. This study provides insight into the genomic effects of the CD diet through the Stat1 expression, which might be involved in NAFLD development. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Higher dietary intakes of choline and betaine are associated with a lower risk of primary liver cancer: a case-control study.

    Science.gov (United States)

    Zhou, Rui-Fen; Chen, Xiao-Lin; Zhou, Zhong-Guo; Zhang, Yao-Jun; Lan, Qiu-Ye; Liao, Gong-Cheng; Chen, Yu-Ming; Zhu, Hui-Lian

    2017-04-06

    The dietary intake of methyl donors is favorably associated with many diseases, but the findings regarding primary liver cancer (PLC) risk are limited. This study investigated the association between the intake of choline, betaine and methionine and PLC risk in adults. This 1:1 matched case-control study enrolled 644 hospital-based PLC patients and 644 community-based controls who were matched by sex and age, in Guangzhou, China. An interviewer-administered questionnaire and a food-frequency questionnaire were used to collect general information and dietary intake information. Conditional logistic regression showed a significantly inverse association between total choline and betaine intakes and PLC risk. The multivariable-adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) for PLC for the top (vs. bottom) tertile were 0.34 (0.24-0.49; P -trend  intake of methionine and PLC risk (P > 0.05). For individual choline compounds, higher consumptions of free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine and sphingomyelin were associated with a lower PLC risk (all P-trend intake (P-interactions: 0.488-0.890). Our findings suggest that higher choline and betaine intakes may be associated with a lower risk of PLC.

  2. Prenatal choline supplementation alters the timing, emotion, and memory performance (TEMP) of adult male and female rats as indexed by differential reinforcement of low-rate schedule behavior.

    Science.gov (United States)

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

    2008-03-01

    Choline availability in the maternal diet has a lasting effect on brain and behavior of the offspring. To further delineate the impact of early nutritional status, we examined effects of prenatal-choline supplementation on timing, emotion, and memory performance of adult male and female rats. Rats that were given sufficient choline (CON: 1.1 g/kg) or supplemental choline (SUP: 5.0 g/kg) during embryonic days (ED) 12-17 were trained with a differential reinforcement of low-rate (DRL) schedule that was gradually transitioned through 5-, 10-, 18-, 36-, and 72-sec criterion times. We observed that SUP-females emitted more reinforced responses than CON-females, which were more efficient than both groups of males. In addition, SUP-males and SUP-females exhibited a reduction in burst responding (response latencies effects of prenatal-choline supplementation were exhibited by reduced frustrative DRL responding in conjunction with the persistence of temporal memory in SUP-males and enhanced temporal exploration and response efficiency in SUP-females.

  3. Regulation of the CDP-choline pathway by sterol regulatory element binding proteins involves transcriptional and post-transcriptional mechanisms.

    Science.gov (United States)

    Ridgway, Neale D; Lagace, Thomas A

    2003-06-15

    The synthesis of phosphatidylcholine (PtdCho) by the CDP-choline pathway is under the control of the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase (CCT). Sterol regulatory element binding proteins (SREBPs) have been proposed to regulate CCT at the transcriptional level, or via the synthesis of lipid activators or substrates of the CDP-choline pathway. To assess the contributions of these two mechanisms, we examined CCTalpha expression and PtdCho synthesis by the CDP-choline pathway in cholesterol and fatty acid auxotrophic CHO M19 cells inducibly expressing constitutively active nuclear forms of SREBP1a or SREBP2. Induction of either SREBP resulted in increased expression of mRNAs for sterol-regulated genes, elevated fatty acid and cholesterol synthesis (>10-50-fold) and increased PtdCho synthesis (2-fold). CCTalpha mRNA was increased 2-fold by enforced expression of SREBP1a or SREBP2. The resultant increase in CCTalpha protein and activity (2-fold) was restricted primarily to the soluble fraction of cells, and increased CCTalpha activity in vivo was not detected. Inhibition of the synthesis of fatty acids or their CoA esters by cerulenin or triacsin C respectively following SREBP induction effectively blocked the accompanying elevation in PtdCho synthesis. Thus PtdCho synthesis was driven by increased synthesis of fatty acids or a product thereof. These data show that transcriptional activation of CCTalpha is modest relative to that of other SREBP-regulated genes, and that stimulation of PtdCho synthesis by SREBPs in CHO cells is due primarily to increased fatty acid synthesis.

  4. PET with {sup 18}F-labelled choline-based tracers for tumour imaging: a review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Mertens, Koen; Lambert, Bieke; Goethals, Ingeborg [University Hospital Ghent, Department of Nuclear Medicine, Gent (Belgium); Slaets, Dominique; Vos, Filip de [University Hospital Ghent, Department of Radiopharmacy, Gent (Belgium); Acou, Marjan [University Hospital Ghent, Department of Radiology, Gent (Belgium)

    2010-11-15

    To give an up-to-date overview of the potential clinical utility of {sup 18}F-labelled choline derivatives for tumour imaging with positron emission tomography. A PubMed search for {sup 18}F-labelled choline analogues was performed. Review articles and reference lists were used to supplement the search findings. {sup 18}F-labelled choline analogues have been investigated as oncological PET probes for many types of cancer on the basis of enhanced cell proliferation. To date, studies have focused on the evaluation of prostate cancer. Available studies have provided preliminary results for detecting local and metastatic disease. Experience with {sup 18}F-fluorocholine PET in other tumour types, including brain and liver tumours, is still limited. In the brain, excellent discrimination between tumour and normal tissue can be achieved due to the low physiological uptake of {sup 18}F-fluorocholine. In the liver, in which there is a moderate to high degree of physiological uptake in normal tissue, malignancy discrimination may be more challenging. PET/CT with {sup 18}F-fluorocholine can be used to detect (recurrent) local prostate cancer, but seems to have limited value for T (tumour) and N (nodal) staging. In patients presenting with recurrent biochemical prostate cancer, it is a suitable single-step examination with the ability to exclude distant metastases when local salvage treatment is intended. In the brain, high-grade gliomas, metastases and benign lesions can be distinguished on the basis of {sup 18}F-fluorocholine uptake. Moreover, PET imaging is able to differentiate between radiation-induced injury and tumour recurrence. In the liver, {sup 18}F-fluorocholine PET/CT seems promising for the detection of hepatocellular carcinoma. (orig.)

  5. 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.

  6. Partial prevention of long-term femoral bone loss in aged ovariectomized rats supplemented with choline-stabilized orthosilicic acid

    OpenAIRE

    Calomme, M.; GEUSENS, Piet; Demeester, N.; Behets, G.; D'Haese, P.; Sindambiwe, J.; Van Hoof, V.; VAN DEN BERGHE, David

    2006-01-01

    Silicon (Si) deficiency in animals results in bone defects. Choline-stabilized orthosilicic acid (ch-OSA) was found to have a high bioavailability compared to other Si supplements. The effect of ch-OSA supplementation was investigated on bone loss in aged ovariectomized (OVX) rats. Female Wistar rats (n = 58, age 9 months) were randomized in three groups. One group was sham-operated (sham, n = 21), and bilateral OVX was performed in the other two groups. OVX rats were supplemented orally with...

  7. 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.

  8. 49 CFR 230.89 - Reverse gear.

    Science.gov (United States)

    2010-10-01

    ... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants shall be maintained in a safe and suitable condition for service. Reverse lever latch shall be so...

  9. Posterior Reversible Encephalopathy (PRES)

    International Nuclear Information System (INIS)

    Moron E, Fanny E; Diaz Marchan, Pedro

    2005-01-01

    The Posterior Reversible Encephalopathy Syndrome (PRES) is a clinical Syndrome composed of cephalea, alteration in vision and convulsions, usually observed in patients with sudden elevation of arterial pressure. The imagenologic evidence shows reversible vasogenic brain edema without stroke. Its location is predominantly posterior; it affects the cortex and the subcortical white matter of the occipital, parietal and temporal lobes. The treatment with antihypertensive drugs and the removing of immunosupressor medication are generally associated with complete neurological recovery; this is reflected also in the images which return to their basal condition. The untreated hypertension, on the other side, can result in a progressive defect of the autoregulation system of the central nervous system with cerebral hemorrhage, irreversible brain stroke, coma and death

  10. CHOLINE TRANSPORTER-LIKE1 is required for sieve plate development to mediate long-distance cell-to-cell communication.

    Science.gov (United States)

    Dettmer, Jan; Ursache, Robertas; Campilho, Ana; Miyashima, Shunsuke; Belevich, Ilya; O'Regan, Seana; Mullendore, Daniel Leroy; Yadav, Shri Ram; Lanz, Christa; Beverina, Luca; Papagni, Antonio; Schneeberger, Korbinian; Weigel, Detlef; Stierhof, York-Dieter; Moritz, Thomas; Knoblauch, Michael; Jokitalo, Eija; Helariutta, Ykä

    2014-07-10

    Phloem, a plant tissue responsible for long-distance molecular transport, harbours specific junctions, sieve areas, between the conducting cells. To date, little is known about the molecular framework related to the biogenesis of these sieve areas. Here we identify mutations at the CHER1/AtCTL1 locus of Arabidopsis thaliana. The mutations cause several phenotypic abnormalities, including reduced pore density and altered pore structure in the sieve areas associated with impaired phloem function. CHER1 encodes a member of a poorly characterized choline transporter-like protein family in plants and animals. We show that CHER1 facilitates choline transport, localizes to the trans-Golgi network, and during cytokinesis is associated with the phragmoplast. Consistent with its function in the elaboration of the sieve areas, CHER1 has a sustained, polar localization in the forming sieve plates. Our results indicate that the regulation of choline levels is crucial for phloem development and conductivity in plants.

  11. Time-reversal acoustics

    Energy Technology Data Exchange (ETDEWEB)

    Fink, Mathias [Laboratoire Ondes et Acoustique, Ecole Superieure de Physique et de Chimie Industrielle de la Ville de Paris, Universite Denis Diderot, UMR CNRS 7587, 10 Rue Vauquelin, 75005 Paris (France)], E-mail: mathias.fink@espci.fr

    2008-10-15

    Time-reversal mirrors (TRMs) refocus an incident acoustic field to the position of the original source regardless of the complexity of the propagation medium. TRM's have now been implemented in a variety of physical scenarios from MHz ultrasonics with order centimeter aperture size to hundreds/thousands of Hz in ocean acoustics with order hundred meter aperture size. Common to this broad range of scales is a remarkable robustness exemplified by observations at all scales that the more complex the medium between the probe source and the TRM, the sharper the focus. The relation between the medium complexity and the size of the focal spot is studied in this paper. It is certainly the most exciting property of TRM compared to standard focusing devices. A TRM acts as an antenna that uses complex environments to appears wider than it is, resulting for a broadband pulse in a refocusing quality that does not depend of the TRM aperture. In this paper, we investigate the time-reversal approach in various media of increasing complexity and we discuss the link existing between time-reversal approach and local helioseismology where Green's functions can be extracted from diffusive noise.

  12. 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.

  13. 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.

  14. 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

  15. 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.)

  16. 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

  17. Status of time reversal invariance

    International Nuclear Information System (INIS)

    Henley, E.M.

    1989-01-01

    Time Reversal Invariance is introduced, and theories for its violation are reviewed. The present experimental and theoretical status of Time Reversal Invariance and tests thereof will be presented. Possible future tests will be discussed

  18. 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

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

    Science.gov (United States)

    Scott, Russell A; Thilmony, Roger; Harden, Leslie A; Zhou, Yaguang; Brandl, Maria T

    2017-01-01

    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 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 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 Δ betTIBA -Δ otsBA 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 MAP cut lettuce. However, its competitive fitness followed a different time-dependent trend in

  20. A Study on Reverse Logistics

    OpenAIRE

    Reddy, Dhananjaya

    2011-01-01

    In the competitive world of manufacturing, companies are often searching for new ways to improve their process, customer satisfaction and stay ahead in the game with their competitors. Reverse logistics has been considered a strategy to bring these things to life for the past decade or so. This thesis work tries to shed some light on the basics of reverse logistics and how reverse logistics can be used as a management strategy. This paper points out the fundamentals of reverse logistics and l...

  1. Adsorption of choline benzoate ionic liquid on graphene, silicene, germanene and boron-nitride nanosheets: a DFT perspective.

    Science.gov (United States)

    García, Gregorio; Atilhan, Mert; Aparicio, Santiago

    2015-07-07

    The adsorption of choline benzoate ([CH][BE]) ionic liquid (IL) on the surface of different hexagonal nanosheets has been studied using Density Functional Theory (DFT) methods. For this, the interaction mechanism, binding energies and electronic structure of [CH][BE] ionic liquid on four types of nanosheets, i.e., graphene, silicene, germanene and boron-nitride, were estimated and compared. The adsorption of [CH][BE] ionic liquid on different nanosheets is mainly featured by van der Waals forces, leading to strong benzoate ion-surface π-stacking. Likewise, there is also an important charge transfer from the anion to the sheet. The electronic structure analysis shows that Si- and Ge-based sheets lead to the largest changes in the HOMO and LUMO levels of choline benzoate. This paper provides new insights into the capability of DFT methods to provide useful information about the adsorption of ionic liquids on nanosheets and how ionic liquid features could be tuned through the adsorption on the suitable nanosheet.

  2. Palm ethyl ester purification by using Choline Chloride – 1,2 propanediol as deep eutectic solvent

    Science.gov (United States)

    Manurung, R.; Alhamdi, M. A.; Syahputra, A.

    2018-02-01

    Deep eutectic solvent (DES) has gained more attention for using in biodiesel production because of environmental benefits and process improvements. This study was aimed to test the potency and effectiveness of Deep Eutectic Solvent (DES) based choline chloride: 1.2-propanediol as co-solvent in biodiesel purification. The method used in preparing DES synthesis process was conducted by mixing choline chloride: 1.2-propanediol with mole ratio variation such as: 1:2 ; 1:2.5 ; 1:3 ; and 1:3.5 (mole/mole). The temperature of DES synthesis was at 80 °C with 300 rpm stirring speed for 60 minutes. Variation of DES concentration base on percentage palm oil used: 1, 3, and 5 %. DES possible to increase the ethyl ester yield of biodiesel in the purification process. The best result of yield was 89.95% with the 9:1 molar ratio ethanol: oil and 5% of DES. The operation condition was at 70 °C of temperature reaction, 400 rpm of stirring speed, and 90 minutes of reaction time.

  3. Mass spectrometry imaging reveals new biological roles for choline esters and Tyrian purple precursors in muricid molluscs

    Science.gov (United States)

    Rudd, David; Ronci, Maurizio; Johnston, Martin R.; Guinan, Taryn; Voelcker, Nicolas H.; Benkendorff, Kirsten

    2015-01-01

    Despite significant advances in chemical ecology, the biodistribution, temporal changes and ecological function of most marine secondary metabolites remain unknown. One such example is the association between choline esters and Tyrian purple precursors in muricid molluscs. Mass spectrometry imaging (MSI) on nano-structured surfaces has emerged as a sophisticated platform for spatial analysis of low molecular mass metabolites in heterogeneous tissues, ideal for low abundant secondary metabolites. Here we applied desorption-ionisation on porous silicon (DIOS) to examine in situ changes in biodistribution over the reproductive cycle. DIOS-MSI showed muscle-relaxing choline ester murexine to co-localise with tyrindoxyl sulfate in the biosynthetic hypobranchial glands. But during egg-laying, murexine was transferred to the capsule gland, and then to the egg capsules, where chemical ripening resulted in Tyrian purple formation. Murexine was found to tranquilise the larvae and may relax the reproductive tract. This study shows that DIOS-MSI is a powerful tool that can provide new insights into marine chemo-ecology. PMID:26324173

  4. 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.

  5. {sup 11}C-Choline PET/CT in patients with hormone-resistant prostate cancer showing biochemical relapse after radical prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Ceci, Francesco; Ambrosini, Valentina; Boschi, Stefano; Fanti, Stefano [University of Bologna, Nuclear Medicine Unit, Department of Haematology Oncology and Laboratory Medicine, Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant' Orsola-Malpighi, Bologna (Italy); Castellucci, Paolo [University of Bologna, Nuclear Medicine Unit, Department of Haematology Oncology and Laboratory Medicine, Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant' Orsola-Malpighi, Bologna (Italy); Azienda Ospedaliero-Unversitaria di Bologna Policlinico Sant' Orsola-Malpighi, UO di Medicina Nucleare, PAD. 30, Bologna (Italy); Mamede, Marcelo [Universidade Federal de Minas Gerais, Molecular Imaging Center, Belo Horizonte (Brazil); Schiavina, Riccardo; Martorana, Giuseppe [University of Bologna, Department of Urology, Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant' Orsola-Malpighi, Bologna (Italy); Rubello, Domenico [' Santa Maria della Misericordia' Hospital, Department of Nuclear Medicine and PET/CT Centre, Rovigo (Italy); Fuccio, Chiara [Fondazione Salvatore Maugeri, Service of Nuclear Medicine, Pavia (Italy)

    2013-02-15

    To determine the diagnostic efficacy of {sup 11}C-choline PET/CT in patients with prostate cancer (PC) after radical prostatectomy who presented with increasing PSA levels during follow-up in spite of being on hormone treatment (HT), and therefore showing HT resistance. We evaluated a large series of 157 consecutive PC patients previously treated by radical prostatectomy who presented with biochemical recurrence with increasing PSA levels in spite of ongoing HT (HT-resistant patients). At the time of {sup 11}C-choline PET/CT, the mean value of trigger PSA level was 8.3 (range 0.2 - 60.6 ng/mL), the mean PSA doubling time (PSAdt) was 5.3 (range 0.4 - 35 months), and the mean PSA velocity (PSAvel) was 22.1 ng/mL/year (range 0.12 - 82 ng/mL/year). {sup 11}C-Choline PET/CT was performed following a standard procedure at our centre to investigate increasing PSA levels, either as the first imaging procedure or in patients with negative conventional imaging. At the time of {sup 11}C-choline PET/CT all patients were receiving HT (61 were receiving monotherapy and 96 multidrug therapy). PET-positive findings were validated by: (a) transrectal US-guided biopsy in patients with recurrence in the prostatic bed, (b) surgical pelvic lymphadenectomy, (c) other imaging modalities, including repeated {sup 11}C-choline PET/CT, performed during a minimum follow-up of 12-months. {sup 11}C-Choline PET/CT showed positive findings in 104 of the 157 patients (66 %). {sup 11}C-choline PET/CT detected: a single lesion in 40 patients (7 in the prostate bed, 10 in lymph nodes, 22 in bone, 1 at another site); two lesions in 18 patients (7 in lymph nodes, 7 in bone, 4 in both lymph nodes and bone); three or four lesions in 7 patients (4 in lymph nodes, 2 in bone, 1 at another site); and more than four lesions in the remaining 39 patients (2 in the prostate bed, 12 in lymph nodes, 12 in bone, 11 in both lymph nodes and bone, 2 at other sites). In {sup 11}C-choline PET-negative patients, the mean

  6. Reversible brazing process

    Science.gov (United States)

    Pierce, Jim D.; Stephens, John J.; Walker, Charles A.

    1999-01-01

    A method of reversibly brazing surfaces together. An interface is affixed to each surface. The interfaces can be affixed by processes such as mechanical joining, welding, or brazing. The two interfaces are then brazed together using a brazing process that does not defeat the surface to interface joint. Interfaces of materials such as Ni-200 can be affixed to metallic surfaces by welding or by brazing with a first braze alloy. The Ni-200 interfaces can then be brazed together using a second braze alloy. The second braze alloy can be chosen so that it minimally alters the properties of the interfaces to allow multiple braze, heat and disassemble, rebraze cycles.

  7. Reversibly Bistable Flexible Electronics

    KAUST Repository

    Alfaraj, Nasir

    2015-05-01

    Introducing the notion of transformational silicon electronics has paved the way for integrating various applications with silicon-based, modern, high-performance electronic circuits that are mechanically flexible and optically semitransparent. While maintaining large-scale production and prototyping rapidity, this flexible and translucent scheme demonstrates the potential to transform conventionally stiff electronic devices into thin and foldable ones without compromising long-term performance and reliability. In this work, we report on the fabrication and characterization of reversibly bistable flexible electronic switches that utilize flexible n-channel metal-oxide-semiconductor field-effect transistors. The transistors are fabricated initially on rigid (100) silicon substrates before they are peeled off. They can be used to control flexible batches of light-emitting diodes, demonstrating both the relative ease of scaling at minimum cost and maximum reliability and the feasibility of integration. The peeled-off silicon fabric is about 25 µm thick. The fabricated devices are transferred to a reversibly bistable flexible platform through which, for example, a flexible smartphone can be wrapped around a user’s wrist and can also be set back to its original mechanical position. Buckling and cyclic bending of such host platforms brings a completely new dimension to the development of flexible electronics, especially rollable displays.

  8. 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)

  9. Choline and Cystine Deficient Diets in Animal Models with Hepatocellular Injury: Evaluation of Oxidative Stress and Expression of RAGE, TNF-α, and IL-1β

    Science.gov (United States)

    Santos, Juliana Célia F.; de Araújo, Orlando R. P.; Valentim, Iara B.; de Andrade, Kívia Queiroz; Moura, Fabiana Andréa; Smaniotto, Salete; dos Santos, John Marques; Gelain, Daniel P.; Goulart, Marília O. F.

    2015-01-01

    This study aims to evaluate the effects of diets deficient in choline and/or cystine on hepatocellular injury in animal models (young male Wistar rats, aged 21 days), by monitoring some of the oxidative stress biomarkers and the expression of RAGE, TNF-α, and IL-1β. The animals were divided into 6 groups (n = 10) and submitted to different diets over 30 days: AIN-93 diet (standard, St), AIN-93 choline deficient (CD) diet and AIN-93 choline and cystine deficient (CCD) diet, in the pellet (pl) and powder (pw) diet forms. Independently of the diet form, AIN-93 diet already led to hepatic steatosis and CD/CCD diets provoked hepatic damage. The increase of lipid peroxidation, represented by the evaluation of thiobarbituric acid reactive species, associated with the decrease of levels of antioxidant enzymes, were the parameters with higher significance toward redox profile in this model of hepatic injury. Regarding inflammation, in relation to TNF-α, higher levels were evidenced in CD(pl), while, for IL-1β, no significant alteration was detected. RAGE expression was practically the same in all groups, with exception of CCD(pw) versus CCD(pl). These results together confirm that AIN-93 causes hepatic steatosis and choline and/or cysteine deficiencies produce important hepatic injury associated with oxidative stress and inflammatory profiles. PMID:26137185

  10. Alpha7 Nicotinic Acetylcholine Receptors and Temporal Memory: Synergistic Effects of Combining Prenatal Choline and Nicotine on Reinforcement-Induced Resetting of an Interval Clock

    Science.gov (United States)

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

    2006-01-01

    We previously showed that prenatal choline supplementation could increase the precision of timing and temporal memory and facilitate simultaneous temporal processing in mature and aged rats. In the present study, we investigated the ability of adult rats to selectively control the reinforcement-induced resetting of an internal clock as a function…

  11. 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

    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...

  12. 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...

  13. 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)

  14. 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

    AIM: To study liver cell apoptosis caused by the toxicity of selenium and observe the alteration of choline compounds using in vitro 9.4T high resolution magnetic resonance spectroscopy. METHODS: Twenty male Wistar rats were randomly divided into two groups. The rats in the treatment group were i...

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

    Directory of Open Access Journals (Sweden)

    Thalles H. Ribeiro

    Full Text Available Summary Early diagnosis and staging of non-Hodgkin lymphoma (NHL is essential for therapeutic strategy decision. Positron emission tomography/computed tomography (PET/CT with fluordeoxyglucose (FDG, a glucose analogue, labeled with fluor-18 (18F-FDG has been used to evaluate staging, therapy response and prognosis in NHL patients. However, in some cases, 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 18F-FDG and 18F-choline PET/CT scan imaging pre- and post-therapy. 18F-FDG and 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 18F-FDG and 18F-choline PET/ CT scans revealed no signs of radiotracer uptake, suggesting complete remission of the tumor. 18F-choline may be a complimentary tool for staging and assessment of therapeutic response in non-Hodgkin lymphoma, while non-18F-FDG tracer can be used for targeted therapy and patient management.

  16. Reversible posterior leukoencephalopathy syndrome

    International Nuclear Information System (INIS)

    Lee, Eun Ja; Yu, Won Jong; Ahn, Kook Jin; Jung, So Lyung; Lee, Yeon Soo; Kim, Ji Chang; Kang, Si Won; Song, Chang Joon; Song, Soon-Young; Koo, Ja Hong; Kim, Man Deuk

    2001-01-01

    To review reversible posterior leukoencephalopathy syndrome. We reviewed 22 patients (M:F=3:19; age, 17-46 years) with the characteristic clinical and imaging features of reversible posterior leukoencephalopathy syndrome. All underwent brain MRI, and in three cases both CT and MRI were performed. In one, MRA was obtained, and in eleven, follow-up MR images were obtained. We evaluated the causes of this syndrome, its clinical manifestations, and MR findings including the locations of lesions, the presence or absence of contrast enhancement, and the changes seen at follow-up MRI. Of the 22 patients, 13 had eclampsia (six during pregnancy and seven during puerperium). Four were receiving immunosuppressive therapy (three, cyclosporine ; one, FK 506). Four suffered renal failure and one had complicated migraine. The clinical manifestations included headache (n=12), visual disturbance (n=13), seizure (n=15), focal neurologic sign (n=3), and altered mental status (n=2). Fifteen patients had hypertension and the others normotension. MRI revealed that lesions were bilateral (n=20) or unilateral (n=2). In all patients the lesion was found in the cortical and subcortical areas of the parieto-occipital lobes ; other locations were the basal ganglia (n=9), posterior temporal lobe (n=8), frontal lobe (n=5), cerebellum (n=5), pons (n=2), and thalamus (n=1). All lesions were of high signal intensity on T2-weighted images, and of iso to low intensity on T1-weighted images. One was combined with acute hematoma in the left basal ganglia. In eight of 11 patients who underwent postcontrast T1-weighted MRI, there was no definite enhancement ; in one, enhancement was mild, and in tow, patchy. CT studies showed low attenuation, and MRA revealed mild vasospasm. The symptoms of all patients improved. Follow-up MRI in nine of 11 patients depicted complete resolution of the lesions ; in two, small infarctions remained but the extent of the lesions had decreased. Reversible posterior

  17. Reversible posterior leukoencephalopathy syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ja; Yu, Won Jong; Ahn, Kook Jin; Jung, So Lyung; Lee, Yeon Soo; Kim, Ji Chang; Kang, Si Won [The Catholic Univ. of Korea, Taejon (Korea, Republic of); Song, Chang Joon [Chungnam National Univ. School of Medicine, Cheonju (Korea, Republic of); Song, Soon-Young; Koo, Ja Hong [Kwandong Univ. College of Medicine, Myungji Hospital, Seoul (Korea, Republic of); Kim, Man Deuk [College of Medicine Pochon CHA Univ., Seoul (Korea, Republic of)

    2001-10-01

    To review reversible posterior leukoencephalopathy syndrome. We reviewed 22 patients (M:F=3:19; age, 17-46 years) with the characteristic clinical and imaging features of reversible posterior leukoencephalopathy syndrome. All underwent brain MRI, and in three cases both CT and MRI were performed. In one, MRA was obtained, and in eleven, follow-up MR images were obtained. We evaluated the causes of this syndrome, its clinical manifestations, and MR findings including the locations of lesions, the presence or absence of contrast enhancement, and the changes seen at follow-up MRI. Of the 22 patients, 13 had eclampsia (six during pregnancy and seven during puerperium). Four were receiving immunosuppressive therapy (three, cyclosporine ; one, FK 506). Four suffered renal failure and one had complicated migraine. The clinical manifestations included headache (n=12), visual disturbance (n=13), seizure (n=15), focal neurologic sign (n=3), and altered mental status (n=2). Fifteen patients had hypertension and the others normotension. MRI revealed that lesions were bilateral (n=20) or unilateral (n=2). In all patients the lesion was found in the cortical and subcortical areas of the parieto-occipital lobes ; other locations were the basal ganglia (n=9), posterior temporal lobe (n=8), frontal lobe (n=5), cerebellum (n=5), pons (n=2), and thalamus (n=1). All lesions were of high signal intensity on T2-weighted images, and of iso to low intensity on T1-weighted images. One was combined with acute hematoma in the left basal ganglia. In eight of 11 patients who underwent postcontrast T1-weighted MRI, there was no definite enhancement ; in one, enhancement was mild, and in tow, patchy. CT studies showed low attenuation, and MRA revealed mild vasospasm. The symptoms of all patients improved. Follow-up MRI in nine of 11 patients depicted complete resolution of the lesions ; in two, small infarctions remained but the extent of the lesions had decreased. Reversible posterior

  18. Differential role of human choline kinase alpha and beta enzymes in lipid metabolism: implications in cancer onset and treatment.

    Directory of Open Access Journals (Sweden)

    David Gallego-Ortega

    Full Text Available BACKGROUND: The Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK is the first enzyme of the Kennedy branch of synthesis of phosphocholine, the major component of the plasma membrane. ChoK family of proteins is composed by ChoKalpha and ChoKbeta isoforms, the first one with two different variants of splicing. Recently ChoKalpha has been implicated in the carcinogenic process, since it is over-expressed in a variety of human cancers. However, no evidence for a role of ChoKbeta in carcinogenesis has been reported. METHODOLOGY/PRINCIPAL FINDINGS: Here we compare the in vitro and in vivo properties of ChoKalpha1 and ChoKbeta in lipid metabolism, and their potential role in carcinogenesis. Both ChoKalpha1 and ChoKbeta showed choline and ethanolamine kinase activities when assayed in cell extracts, though with different affinity for their substrates. However, they behave differentially when overexpressed in whole cells. Whereas ChoKbeta display an ethanolamine kinase role, ChoKalpha1 present a dual choline/ethanolamine kinase role, suggesting the involvement of each ChoK isoform in distinct biochemical pathways under in vivo conditions. In addition, while overexpression of ChoKalpha1 is oncogenic when overexpressed in HEK293T or MDCK cells, ChoKbeta overexpression is not sufficient to induce in vitro cell transformation nor in vivo tumor growth. Furthermore, a significant upregulation of ChoKalpha1 mRNA levels in a panel of breast and lung cancer cell lines was found, but no changes in ChoKbeta mRNA levels were observed. Finally, MN58b, a previously described potent inhibitor of ChoK with in vivo antitumoral activity, shows more than 20-fold higher efficiency towards ChoKalpha1 than ChoKbeta. CONCLUSION/SIGNIFICANCE: This study represents the first evidence of the distinct metabolic role of ChoKalpha and ChoKbeta isoforms, suggesting different physiological roles and implications in human

  19. 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

  20. Accuracy of tumor segmentation from multi-parametric prostate MRI and18F-choline PET/CT for focal prostate cancer therapy applications.

    Science.gov (United States)

    Piert, Morand; Shankar, Prasad R; Montgomery, Jeffrey; Kunju, Lakshmi Priya; Rogers, Virginia; Siddiqui, Javed; Rajendiran, Thekkelnaycke; Hearn, Jason; George, Arvin; Shao, Xia; Davenport, Matthew S

    2018-03-27

    The study aims to assess the accuracy of multi-parametric prostate MRI (mpMRI) and 18 F-choline PET/CT in tumor segmentation for clinically significant prostate cancer. 18 F-choline PET/CT and 3 T mpMRI were performed in 10 prospective subjects prior to prostatectomy. All subjects had a single biopsy-confirmed focus of Gleason ≥ 3+4 cancer. Two radiologists (readers 1 and 2) determined tumor boundaries based on in vivo mpMRI sequences, with clinical and pathologic data available. 18 F-choline PET data were co-registered to T2-weighted 3D sequences and a semi-automatic segmentation routine was used to define tumor volumes. Registration of whole-mount surgical pathology to in vivo imaging was conducted utilizing two ex vivo prostate specimen MRIs, followed by gross sectioning of the specimens within a custom-made 3D-printed plastic mold. Overlap and similarity coefficients of manual segmentations (seg1, seg2) and 18 F-choline-based segmented lesions (seg3) were compared to the pathologic reference standard. All segmentation methods greatly underestimated the true tumor volumes. Human readers (seg1, seg2) and the PET-based segmentation (seg3) underestimated an average of 79, 80, and 58% of the tumor volumes, respectively. Combining segmentation volumes (union of seg1, seg2, seg3 = seg4) decreased the mean underestimated tumor volume to 42% of the true tumor volume. When using the combined segmentation with 5 mm contour expansion, the mean underestimated tumor volume was significantly reduced to 0.03 ± 0.05 mL (2.04 ± 2.84%). Substantial safety margins up to 11-15 mm were needed to include all tumors when the initial segmentation boundaries were drawn by human readers or the semi-automated 18 F-choline segmentation tool. Combining MR-based human segmentations with the metabolic information based on 18 F-choline PET reduced the necessary safety margin to a maximum of 9 mm to cover all tumors entirely. To improve the outcome of focal therapies for

  1. Robustness of Radiomic Features in [11C]Choline and [18F]FDG PET/CT Imaging of Nasopharyngeal Carcinoma: Impact of Segmentation and Discretization.

    Science.gov (United States)

    Lu, Lijun; Lv, Wenbing; Jiang, Jun; Ma, Jianhua; Feng, Qianjin; Rahmim, Arman; Chen, Wufan

    2016-12-01

    Radiomic features are increasingly utilized to evaluate tumor heterogeneity in PET imaging and to enable enhanced prediction of therapy response and outcome. An important ingredient to success in translation of radiomic features to clinical reality is to quantify and ascertain their robustness. In the present work, we studied the impact of segmentation and discretization on 88 radiomic features in 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) and [ 11 C]methyl-choline ([ 11 C]choline) positron emission tomography/X-ray computed tomography (PET/CT) imaging of nasopharyngeal carcinoma. Forty patients underwent [ 18 F]FDG PET/CT scans. Of these, nine patients were imaged on a different day utilizing [ 11 C]choline PET/CT. Tumors were delineated using reference manual segmentation by the consensus of three expert physicians, using 41, 50, and 70 % maximum standardized uptake value (SUV max ) threshold with background correction, Nestle's method, and watershed and region growing methods, and then discretized with fixed bin size (0.05, 0.1, 0.2, 0.5, and 1) in units of SUV. A total of 88 features, including 21 first-order intensity features, 10 shape features, and 57 second- and higher-order textural features, were extracted from the tumors. The robustness of the features was evaluated via the intraclass correlation coefficient (ICC) for seven kinds of segmentation methods (involving all 88 features) and five kinds of discretization bin size (involving the 57 second- and higher-order features). Forty-four (50 %) and 55 (63 %) features depicted ICC ≥0.8 with respect to segmentation as obtained from [ 18 F]FDG and [ 11 C]choline, respectively. Thirteen (23 %) and 12 (21 %) features showed ICC ≥0.8 with respect to discretization as obtained from [ 18 F]FDG and [ 11 C]choline, respectively. Six features were obtained from both [ 18 F]FDG and [ 11 C]choline having ICC ≥0.8 for both segmentation and discretization, five of which were gray-level co-occurrence matrix

  2. Reverse photoacoustic standoff spectroscopy

    Science.gov (United States)

    Van Neste, Charles W [Kingston, TN; Senesac, Lawrence R [Knoxville, TN; Thundat, Thomas G [Knoxville, TN

    2011-04-12

    A system and method are disclosed for generating a reversed photoacoustic spectrum at a greater distance. A source may emit a beam to a target and a detector measures signals generated as a result of the beam being emitted on the target. By emitting a chopped/pulsed light beam to the target, it may be possible to determine the target's optical absorbance by monitoring the intensity of light collected at the detector at different wavelengths. As the wavelength of light is changed, the target may absorb or reject each optical frequency. Rejection may increase the intensity at the sensing element and absorption may decrease the intensity. Accordingly, an identifying spectrum of the target may be made with the intensity variation of the detector as a function of illuminating wavelength.

  3. Reverse Osmosis Optimization

    Energy Technology Data Exchange (ETDEWEB)

    McMordie Stoughton, Kate; Duan, Xiaoli; Wendel, Emily M.

    2013-08-26

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). ¬The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.¬

  4. Reverse Osmosis Optimization

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-08-01

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.

  5. Reverse osmosis application studies

    International Nuclear Information System (INIS)

    Golomb, A.

    1982-02-01

    To assess the feasibility of applying reverse osmosis (RO) and ultrafiltration (UF) for effective treatment of process and waste streams from operations at Ontario Hydro's thermal and nuclear stations, an extensive literature survey has been carried out. It is concluded that RO is not at present economic for pretreatment of Great Lakes water prior to ion exchange demineralization for boiler makeup. Using both conventional and novel commercial membrane modules, RO pilot studies are recommended for treatment of boiler cleaning wastes, fly ash leachates, and flue gas desulphurization scrubber discharges for removal of heavy metals. Volume reduction and decontamination of nuclear station low-level active liquid waste streams by RO/UF also appear promising. Research programmes are proposed

  6. Sex Reversal in Amphibians.

    Science.gov (United States)

    Flament, Stéphane

    2016-01-01

    Amphibians have been widely used to study developmental biology due to the fact that embryo development takes place independently of the maternal organism and that observations and experimental approaches are easy. Some amphibians like Xenopus became model organisms in this field. In the first part of this article, the differentiation of the gonads in amphibians and the mechanisms governing this process are reviewed. In the second part, the state of the art about sex reversal, which can be induced by steroid hormones in general and by temperature in some species, is presented. Also information about pollutants found in the environment that could interfere with the development of the amphibian reproductive apparatus or with their reproductive physiology is given. Such compounds could play a part in the amphibian decline, since in the wild, many amphibians are endangered species. © 2016 S. Karger AG, Basel.

  7. 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.

  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. 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.

  10. 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.

  11. 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%).

  12. 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.

  13. Heraclitus, Seaford and Reversible Exchange

    OpenAIRE

    Kassam, C; Duschinsky, Robert Nathan

    2017-01-01

    In this essay we identify a characteristic pattern of Heraclitus’ thought and language, the “figure of reversible exchange”. We suggest that this figure allows Heraclitus to propose an ontological structure consisting of two intersecting circuits of relations: a pre-temporal reversible exchange between Being and Becoming and between One and Many, and a temporal reversible exchange within the Many as the very process of Becoming. Against Richard Seaford’s interpretation of Heraclitus’ thought ...

  14. MODELS OF PROJECT REVERSE ENGINEERING

    OpenAIRE

    Віктор Володимирович ІВАНОВ

    2017-01-01

    Reverse engineering decided important scientific and technical problems of increasing the cost of the existing technical product by transforming it into a product with other features or design. Search ideas of the new application of existing products on the base of heuristic analysis were created. The concept of reverse engineering and its division into three types: conceptual, aggregate and complete was expanded. The use of heuristic methods for reverse engineering concept was showed. The mo...

  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. Initiation of HIV Reverse Transcription

    Directory of Open Access Journals (Sweden)

    Roland Marquet

    2010-01-01

    Full Text Available Reverse transcription of retroviral genomes into double stranded DNA is a key event for viral replication. The very first stage of HIV reverse transcription, the initiation step, involves viral and cellular partners that are selectively packaged into the viral particle, leading to an RNA/protein complex with very specific structural and functional features, some of which being, in the case of HIV-1, linked to particular isolates. Recent understanding of the tight spatio-temporal regulation of reverse transcription and its importance for viral infectivity further points toward reverse transcription and potentially its initiation step as an important drug target.

  17. Physics of field reversed mirrors

    International Nuclear Information System (INIS)

    Post, R.F.

    1978-01-01

    Since the earliest days of fusion research it has been hoped that diamagnetic currents flowing in a plasma could be used to help confine the plasma. Recently this hope has been strengthened both by theoretical advances and by experimental results made possible by technological developments. On the theoretical front analytical treatments and computer simulation studies have demonstrated equilibrium solutions existing both in the fluid limit and in the large-orbit limit. Progress has also been made in determining the conditions required for the stability of field-reversed entities. It appears that configurations of the general form of fat doughnuts, possibly elongated to napkin-ring form, represent stable states. Building on previous experimental work, several investigators have been able to create field-reversed states. One method, based on the ASTRON idea of Christofilos, traps an intense relativistic electron beams (REB) to create a field-reversing current ring. Other approaches use either the reversed field theta pinch technique or REB pulses to create field-reversing diamagnetic currents in a long cylindrical plasma. In the former method, millisecond-long field-reversing electron rings have been achieved; in the latter method field-reversed plasma states lasting 30 to 50 microseconds have been achieved. Another approach under investigation is the Field Reversed Mirror (FRM) created by the tangential injection of high current neutral beams. Plasma states that approach field reversal have been achieved by this technique

  18. A reversible processor architecture and its reversible logic design

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Axelsen, Holger Bock; Glück, Robert

    2012-01-01

    We describe the design of a purely reversible computing architecture, Bob, and its instruction set, BobISA. The special features of the design include a simple, yet expressive, locally-invertible instruction set, and fully reversible control logic and address calculation. We have designed an arch...

  19. Enzymatic reactions in reversed micelles

    NARCIS (Netherlands)

    Hilhorst, M.H.

    1984-01-01

    It has been recognised that enzymes in reversed micelles have potential for application in chemical synthesis. Before these expectations will be realised many problems must be overcome. This thesis deals with some of them.
    In Chapter 1 the present knowledge about reversed micelles and

  20. REVERSE LOGISTICS IN GLOBALIZATION ASPECTS

    OpenAIRE

    Janusz Grabara; Iwona Grabara

    2008-01-01

    This paper presents issues connected with adaptation of modern solutions of reverse logisticsmanagement in enterprise to the concept of sustainable development promoted by the European Union.Nowadays more and more businesses are looking to grow their reverse logistics capabilities in global market.

  1. Enzyme recovery using reversed micelles

    NARCIS (Netherlands)

    Dekker, M.

    1990-01-01

    The objective of this study was to develop a liquid-liquid extraction process for the recovery of extracellular enzymes. The potentials of reaching this goal by using reversed micelles in an organic solvent have been investigated.

    Reversed micelles are aggregates of surfactant

  2. Reverse genetics of avian metapneumoviruses

    Science.gov (United States)

    An overview of avian metapneumovirus (aMPV) infection in turkeys and development of a reverse genetics system for aMPV subgroup C (aMPV-C) virus will be presented. By using reverse genetics technology, we generated recombinant aMPV-C viruses containing a different length of glycoprotein (G) gene or...

  3. Reference counting for reversible languages

    DEFF Research Database (Denmark)

    Mogensen, Torben Ægidius

    2014-01-01

    Modern programming languages and operating systems use heap memory that allows allocation and deallocation of memory to be decoupled, so they don't follow a stack discipline. Axelsen and Glück have presented a reversible heap manager where allocation and deallocation are each other's logical...... inverses: Freeing a block of memory is done by running the allocation procedure backwards. Axelsen and Glück use this heap manager to sketch implementation of a simple reversible functional language where pattern matching a constructor is the inverse of construction, so pattern-matching implies...... a pointer decreases the reference count. We show reversible implementations of operations on nodes with reference counts. We then show these operations can be used when implementing a reversible functional language RCFUN to the reversible imperative language Janus....

  4. Reversible gates and circuits descriptions

    Science.gov (United States)

    Gracki, Krzystof

    2017-08-01

    This paper presents basic methods of reversible circuit description. To design reversible circuit a set of gates has to be chosen. Most popular libraries are composed of three types of gates so called CNT gates (Control, NOT and Toffoli). The gate indexing method presented in this paper is based on the CNT gates set. It introduces a uniform indexing of the gates used during synthesis process of reversible circuits. The paper is organized as follows. Section 1 recalls basic concepts of reversible logic. In Section 2 and 3 a graphical representation of the reversible gates and circuits is described. Section 4 describes proposed uniform NCT gates indexing. The presented gate indexing method provides gate numbering scheme independent of lines number of the designed circuit. The solution for a circuit consisting of smaller number of lines is a subset of solution for a larger circuit.

  5. MODELS OF PROJECT REVERSE ENGINEERING

    Directory of Open Access Journals (Sweden)

    Віктор Володимирович ІВАНОВ

    2017-03-01

    Full Text Available Reverse engineering decided important scientific and technical problems of increasing the cost of the existing technical product by transforming it into a product with other features or design. Search ideas of the new application of existing products on the base of heuristic analysis were created. The concept of reverse engineering and its division into three types: conceptual, aggregate and complete was expanded. The use of heuristic methods for reverse engineering concept was showed. The modification model of Reverse engineering based on the model of РМВОК was developed. Our model includes two new phases: identification and transformation. At the identification phase, technical control is made. At the transformation phase, search heuristic idea of the new applied existing technical product was made. The model of execution phase that included heuristic methods, metrological equipment, and CAD/CAM/CAE program complex was created. The model that connected economic indicators of reverse engineering project was developed.

  6. Fundamentals of reversible flowchart languages

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2016-01-01

    Abstract This paper presents the fundamentals of reversible flowcharts. They are intended to naturally represent the structure and control flow of reversible (imperative) programming languages in a simple computation model, in the same way classical flowcharts do for conventional languages......, structured reversible flowcharts are as expressive as unstructured ones, as shown by a reversible version of the classic Structured Program Theorem. We illustrate how reversible flowcharts can be concretized with two example programming languages, complete with syntax and semantics: a low-level unstructured...... language and a high-level structured language. We introduce concrete tools such as program inverters and translators for both languages, which follow the structure suggested by the flowchart model. To further illustrate the different concepts and tools brought together in this paper, we present two major...

  7. 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.

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

    Science.gov (United States)

    Roe, Annie J; Zhang, Shucha; Bhadelia, Rafeeque A; Johnson, Elizabeth J; Lichtenstein, Alice H; Rogers, Gail T; Rosenberg, Irwin H; Smith, Caren E; Zeisel, Steven H; Scott, Tammy M

    2017-06-01

    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 cardiovascular disease, and cerebrovascular pathology. Design: A cross-sectional subset of the Nutrition, Aging, and Memory in Elders cohort who had undergone MRI of the brain ( n = 296; mean ± SD age: 73 ± 8.1 y) was assessed. Plasma concentrations of free choline, betaine, and phosphatidylcholine were measured with the use of liquid-chromatography-stable-isotope dilution-multiple-reaction monitoring-mass spectrometry. A volumetric analysis of MRI was used to determine the cerebrovascular pathology (white-matter hyperintensities and small- and large-vessel infarcts). Multiple linear and logistic regression models were used to examine relations of plasma measures with cardiometabolic risk factors, history of cardiovascular disease, and radiologic evidence of cerebrovascular pathology. Results: Higher concentrations of plasma choline were associated with an unfavorable cardiometabolic risk-factor profile [lower high-density lipoprotein (HDL) cholesterol, higher total homocysteine, and higher body mass index (BMI)] and greater odds of large-vessel cerebral vascular disease or history of cardiovascular disease but lower odds of small-vessel cerebral vascular disease. Conversely, higher concentrations of plasma betaine were associated with a favorable cardiometabolic risk-factor profile [lower low-density lipoprotein (LDL) cholesterol and triglycerides] and lower odds of diabetes. Higher concentrations of plasma phosphatidylcholine were associated with characteristics of both a favorable cardiometabolic risk-factor profile (higher HDL cholesterol, lower BMI, lower C-reactive protein, lower waist circumference, and lower odds of hypertension and diabetes) and an unfavorable profile

  9. Do androgens control the uptake of {sup 18}F-FDG, {sup 11}C-choline and {sup 11}C-acetate in human prostate cancer cell lines?

    Energy Technology Data Exchange (ETDEWEB)

    Emonds, Kimy M.; Nuyts, Johan; Mortelmans, Luc [University Hospital Gasthuisberg Leuven, Department of Nuclear Medicine, Leuven (Belgium); Swinnen, Johannes V.; Vanderhoydonc, Frank [K.U. Leuven, Laboratory for Experimental Medicine and Endocrinology, Department of Experimental Medicine, Leuven (Belgium); Weerden, Wytske M. van [Erasmus University Rotterdam, Department of Experimental Urology, Josephine Nefkens Institute, Rotterdam (Netherlands); Mottaghy, Felix M. [University Hospital Gasthuisberg Leuven, Department of Nuclear Medicine, Leuven (Belgium); University Hospital Aachen, Department of Nuclear Medicine, Aachen (Germany); Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands)

    2011-10-15

    The aim of this study was to evaluate the impact of androgen ablation therapy in different prostate cancer (PCa) cell lines - reflecting different stages of the disease - on {sup 18}F-fluorodeoxyglucose (FDG), {sup 11}C-choline and {sup 11}C-acetate uptake. Uptake experiments were performed in androgen-sensitive (LNCaP, PC346C) and independent cell lines (22Rv1, PC346DCC, PC-3) as well as in a benign prostatic hyperplasia (BPH-1) cell line. Tracer uptake was assessed under androgen ablation. Results of the cancer cell lines were normalized to those of BPH-1. To evaluate the effect of androgen on the uptake of {sup 18}F-FDG, {sup 11}C-choline and {sup 11}C-acetate in PCa cell lines, 10{sup -8}M R1881, 10{sup -10}M R1881, the combination of 10{sup -10}M R1881 plus 10{sup -6}M Casodex or 10{sup -6}M Casodex alone were added in parallel cell cultures 1 day before uptake experiments. Uptake in androgen-supplemented cell cultures was compared to the uptake under androgen deprivation. Uptake was corrected for cell number using protein content. Compared to BPH-1, a higher {sup 18}F-FDG uptake was observed only in PC346C cells, whereas a higher {sup 11}C-choline and markedly increased {sup 11}C-acetate uptake was seen in all cancer cell lines. Androgens significantly modulated the uptake of {sup 18}F-FDG in LNCaP, PC346C and 22Rv1 cells, and of {sup 11}C-choline in the PC346C and 22Rv1 cell line. No androgenic effect on {sup 11}C-choline and {sup 18}F-FDG uptake was observed in PC-3 and PC346DCC cells. {sup 11}C-Acetate uptake was independent of androgen status in all PCa cell lines studied. {sup 18}F-FDG uptake in PCa cell lines showed the highest variability and strongest androgen effect, suggesting its poor potential for metabolic imaging of advanced PCa. In contrast to {sup 18}F-FDG and {sup 11}C-choline, {sup 11}C-acetate uptake was unaffected by androgens and thus {sup 11}C-acetate seems best for monitoring PCa progression. (orig.)

  10. 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

  11. Diagnostic accuracy of {sup 11}C-choline PET/CT in comparison with CT and/or MRI in patients with hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lopci, Egesta [Nuclear Medicine Department, Humanitas Clinical and Research Center, Rozzano, MI (Italy); Torzilli, Guido; Donadon, Matteo; Palmisano, Angela [Hepatobiliary Surgery, Humanitas Clinical and Research Center, Rozzano, MI (Italy); Poretti, Dario; Lanza, Ezio; Pedicini, Vittorio [Radiology Unit, Humanitas Clinical and Research Center, Rozzano, MI (Italy); Neto, Lauro J.S. de; Sabongi, Juliano Guerra [Medicina Nuclear, Centro Medico Imagem, Sorocaba (Brazil); Rimassa, Lorenza; Personeni, Nicola [Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center, Rozzano, MI (Italy); Ceriani, Roberto [Hepatology Unit, Humanitas Clinical and Research Center, Rozzano, MI (Italy); Comito, Tiziana; Scorsetti, Marta [Radiosurgery and Radiotherapy, Humanitas Clinical and Research Center, Rozzano, MI (Italy); Chiti, Arturo [Nuclear Medicine Department, Humanitas Clinical and Research Center, Rozzano, MI (Italy); Humanitas University, Chair of Diagnostic Imaging, Rozzano, MI (Italy)

    2015-08-15

    In recent decades, the use of radiopharmaceuticals in the assessment of hepatocellular carcinoma (HCC) has become established, and new findings indicate that radiolabelled choline has considerable potential in this setting. Therefore, in this study we aimed to assess the diagnostic role of {sup 11}C-choline positron emission tomography (PET)/CT, compared with conventional imaging with CT/MRI, in patients with HCC. The study population comprised 45 patients (male to female ratio = 37:8, median age 70.5 years) referred to our institution owing to HCC: 27 at initial diagnosis and 18 for restaging after recurrence. In all cases we performed whole-body {sup 11}C-choline PET/CT and compared its findings with contrast-enhanced CT (n = 35) or MRI (n = 29) or both (n = 15) for a total of 50 paired scans. The reference standard was either histological proof (21 patients) or a multidisciplinary consensus. Diagnostic accuracy was then determined in a scan-based (SBA) and a lesion-based analysis (LBA). On SBA the sensitivity and specificity for PET were 88 and 90 %, respectively, whereas for CT/MRI they were 90 and 73 %, respectively (p > 0.05). On LBA the overall sensitivity and specificity were 78 and 86 %, respectively, for PET vs 65 and 55 % for CT/MRI. Overall we investigated 168 disease sites, of which 100 were in the liver and 68 were extrahepatic. When considering only liver lesions, {sup 11}C-choline PET and CT/MRI showed an accuracy of 66 and 85 %, respectively, while for extrahepatic lesions PET showed an accuracy of 99 %, while the accuracy of CT/MRI was 32 %. In both cases, there was a statistically significant difference in accuracy between the two modalities (p < 0.01). Combination of the PET results with those of CT/MRI resulted in the highest diagnostic accuracy in both analyses, at 92 % for SBA and 96 % for LBA. In 11 patients (24 %) the PET findings modified the therapeutic strategy, the modification proving appropriate in 10 of them. {sup 11}C-Choline PET

  12. Biotinidase deficiency: a reversible metabolic encephalopathy. Neuroimaging and MR spectroscopic findings in a series of four patients

    International Nuclear Information System (INIS)

    Desai, Shrinivas; Ganesan, Karthik; Hegde, Anaita

    2008-01-01

    Biotinidase deficiency is a metabolic disorder characterized by inability to recycle biotin with resultant delayed myelination. Clinical findings include seizures, ataxia, alopecia and dermatitis with atypical findings of myoclonic jerks, neuropathy and spastic paraparesis. Neuroradiological findings include cerebral atrophy, encephalopathy and widened extracerebral CSF spaces. Many of the clinical and neuroradiological features are reversible except sensorineural hearing loss and optic atrophy. To understand and describe the neuroimaging and spectroscopic findings of biotinidase deficiency. We evaluated the spectrum of neuroimaging and spectroscopic findings in four patients with biotinidase deficiency with follow-up studies in three patients. The imaging findings were encephalopathy, low cerebral volume, ventriculomegaly and widened extracerebral CSF spaces. Uncommon findings were caudate involvement, parieto-occipital cortical abnormalities and one patient with restricted diffusion. Two patients had subdural effusions, which is uncommon in biotinidase deficiency. 1 H-MR spectroscopy revealed elevated lactate, reversal of the choline/creatine ratio and decreased NAA peaks. Follow-up studies revealed complete reversal of imaging findings in two patients. Biotinidase deficiency is a reversible metabolic encephalopathy. This study highlights the importance of early and prompt cliniconeuroradiological diagnosis of biotinidase deficiency as it has an extremely good clinical outcome if treatment is initiated from early infancy. (orig.)

  13. Biotinidase deficiency: a reversible metabolic encephalopathy. Neuroimaging and MR spectroscopic findings in a series of four patients

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Shrinivas [Jaslok Hospital and Research Centre, Department of CT and MRI, Mumbai (India); Ganesan, Karthik [Jaslok Hospital and Research Centre, Department of CT and MRI, Mumbai (India); University of California, San Diego, Department of Radiology, San Diego, CA (United States); Hegde, Anaita [Jaslok Hospital and Research Centre, Department of Paediatrics, Mumbai (India)

    2008-08-15

    Biotinidase deficiency is a metabolic disorder characterized by inability to recycle biotin with resultant delayed myelination. Clinical findings include seizures, ataxia, alopecia and dermatitis with atypical findings of myoclonic jerks, neuropathy and spastic paraparesis. Neuroradiological findings include cerebral atrophy, encephalopathy and widened extracerebral CSF spaces. Many of the clinical and neuroradiological features are reversible except sensorineural hearing loss and optic atrophy. To understand and describe the neuroimaging and spectroscopic findings of biotinidase deficiency. We evaluated the spectrum of neuroimaging and spectroscopic findings in four patients with biotinidase deficiency with follow-up studies in three patients. The imaging findings were encephalopathy, low cerebral volume, ventriculomegaly and widened extracerebral CSF spaces. Uncommon findings were caudate involvement, parieto-occipital cortical abnormalities and one patient with restricted diffusion. Two patients had subdural effusions, which is uncommon in biotinidase deficiency. {sup 1}H-MR spectroscopy revealed elevated lactate, reversal of the choline/creatine ratio and decreased NAA peaks. Follow-up studies revealed complete reversal of imaging findings in two patients. Biotinidase deficiency is a reversible metabolic encephalopathy. This study highlights the importance of early and prompt cliniconeuroradiological diagnosis of biotinidase deficiency as it has an extremely good clinical outcome if treatment is initiated from early infancy. (orig.)

  14. Supercritical fluid reverse micelle separation

    Science.gov (United States)

    Fulton, J.L.; Smith, R.D.

    1993-11-30

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W[sub o] that determines the maximum size of the reverse micelles. The maximum ratio W[sub o] of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions. 27 figures.

  15. Supercritical fluid reverse micelle separation

    Science.gov (United States)

    Fulton, John L.; Smith, Richard D.

    1993-01-01

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W.sub.o that determines the maximum size of the reverse micelles. The maximum ratio W.sub.o of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions.

  16. A Typology of Reverse Innovation

    DEFF Research Database (Denmark)

    von Zedtwitz, Max; Corsi, Simone; Søberg, Peder Veng

    2015-01-01

    Reverse innovation commonly refers to an innovation initially launched in a developing country and later introduced to an advanced country. Adopting a linear innovation model with the four sequential phases of concept ideation, product development, primary target market introduction, and subsequent...... secondary market introduction, this study expands the espoused definition of reverse innovation beyond its market-introduction focus with reversals in the flow of innovation in the ideation and product development phases. Recognizing that each phase can take place in different geographical locations...

  17. Reverse engineering for quality systems

    International Nuclear Information System (INIS)

    Nolan, A.J.

    1995-01-01

    When the age of software engineering began, many companies were faced with a problem of how to support the older, pre-software-engineering, programs. The techniques of reverse engineering and re-engineering were developed to bridge the gap between the past and the present. Although reverse engineering can be used for generating missing documentation, it can also be used as a means to demonstrate quality in these older programs. This paper presents, in the form of a case study, how Rolls-Royce and Associates Limited addressed the quality issues of reverse engineering and re-engineering. (author)

  18. Zero field reversal probability in thermally assisted magnetization reversal

    Science.gov (United States)

    Prasetya, E. B.; Utari; Purnama, B.

    2017-11-01

    This paper discussed about zero field reversal probability in thermally assisted magnetization reversal (TAMR). Appearance of reversal probability in zero field investigated through micromagnetic simulation by solving stochastic Landau-Lifshitz-Gibert (LLG). The perpendicularly anisotropy magnetic dot of 50×50×20 nm3 is considered as single cell magnetic storage of magnetic random acces memory (MRAM). Thermally assisted magnetization reversal was performed by cooling writing process from near/almost Curie point to room temperature on 20 times runs for different randomly magnetized state. The results show that the probability reversal under zero magnetic field decreased with the increase of the energy barrier. The zero-field probability switching of 55% attained for energy barrier of 60 k B T and the reversal probability become zero noted at energy barrier of 2348 k B T. The higest zero-field switching probability of 55% attained for energy barrier of 60 k B T which corespond to magnetif field of 150 Oe for switching.

  19. Diagnostic accuracy of C-11 choline and C-11 acetate for lymph node staging in patients with bladder cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Kim, Seong-Jang; Koo, Phillip J; Pak, Kyoungjune; Kim, In-Ju; Kim, Keunyoung

    2018-03-01

    We aimed to assess the diagnostic accuracy of C-11 choline and C-11 acetate positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging in bladder cancer (BC) patients through a systematic review and meta-analysis. The MEDLINE, EMBASE, and Cochrane Library database, from the earliest available date of indexing through June 30, 2017, were searched for studies evaluating the diagnostic performance of C-11 choline and C-11 acetate PET/CT for LN staging in BC. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves. Across 10 studies (282 patients), the pooled sensitivity was 0.66 (95% CI 0.54-0.75) without heterogeneity (χ 2  = 12.4, p = 0.19) and a pooled specificity of 0.89 (95% CI 0.76-0.95) with heterogeneity (χ 2  = 29.1, p = 0.00). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 5.8 (95% CI 2.7-12.7) and negative likelihood ratio (LR-) of 0.39 (95% CI 0.28-0.53). The pooled diagnostic odds ratio (DOR) was 15 (95% CI 6-38). In meta-regression analysis, the study design (prospective vs retrospective) was the source of the study heterogeneity. C-11 choline and C-11 acetate PET/CT shows a low sensitivity and moderate specificity for the detection of metastatic LNs in patients with BC. Moreover, heterogeneity among the studies should be considered a limitation. Further large multicenter studies would be necessary to substantiate the diagnostic accuracy of C-11 choline and C-11 acetate PET/CT for this purpose.

  20. Higher dietary intakes of choline and betaine are associated with a lower risk of primary liver cancer: a case-control study

    OpenAIRE

    Zhou, Rui-fen; Chen, Xiao-Lin; Zhou, Zhong-guo; Zhang, Yao-jun; Lan, Qiu-ye; Liao, Gong-cheng; Chen, Yu-ming; Zhu, Hui-lian

    2017-01-01

    The dietary intake of methyl donors is favorably associated with many diseases, but the findings regarding primary liver cancer (PLC) risk are limited. This study investigated the association between the intake of choline, betaine and methionine and PLC risk in adults. This 1:1 matched case-control study enrolled 644 hospital-based PLC patients and 644 community-based controls who were matched by sex and age, in Guangzhou, China. An interviewer-administered questionnaire and a food-frequency ...

  1. Dioctanoylglycerol stimulates accumulation of [methyl-14C]choline and its incorporation into acetylcholine and phosphatidylcholine in a human cholinergic neuroblastoma cell line

    Science.gov (United States)

    Slack, B. E.; Richardson, U. I.; Nitsch, R. M.; Wurtman, R. J.

    1992-01-01

    Dioctanoylglycerol, a synthetic diacylglycerol, stimulated [14C]choline uptake in cultured human neuroblastoma (LA-N-2) cells. As this effect has not, to our knowledge, been reported before, it was of interest to characterize it in more detail. In the presence of 500 microM dioctanoylglycerol the levels of [14C]choline attained during a 2 hour labeling period were elevated by 78 +/- 12%, while [14C]acetylcholine and long fatty acyl chain [14C]phosphatidylcholine levels increased by 26 +/- 2% and 19 +/- 5%, respectively (mean +/- S.E.M.). Total (long chain plus dioctanoyl-) [14C]phosphatidylcholine was increased by 198 +/- 33%. Kinetic analysis showed that dioctanoylglycerol reduced the apparent Km for choline uptake to 56 +/- 9% of control (n = 4). The Vmax was not significantly altered. The stimulation of [14C]choline accumulation by dioctanoylglycerol was not dependent on protein kinase C activation; the effect was not mimicked by phorbol ester or by 1-oleoyl-2-acetylglycerol, and was not inhibited by the protein kinase C inhibitors H-7 or staurosporine, or by prolonged pretreatment with phorbol 12-myristate 13-acetate. The effect of dioctanoylglycerol was slightly (but not significantly) reduced by EGTA and strongly inhibited by the cell-permeant calcium chelator bis(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid, tetra(acetoxymethyl)ester. Although these results implicate elevated intracellular calcium in the response, dioctanoylglycerol did not increase phosphatidylinositol hydrolysis in LA-N-2 cells, and its effect was not inhibited by the diacylglycerol kinase inhibitor R 59 022 (which blocks the conversion of diacylglycerol to phosphatidic acid, a known stimulator of phosphatidylinositol hydrolysis).(ABSTRACT TRUNCATED AT 250 WORDS).

  2. 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.)

  3. 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.

  4. 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.

  5. Catalytic dehydration of carbohydrates suspended in organic solvents promoted by AlCl3 /SiO2 coated with choline chloride.

    Science.gov (United States)

    Yang, Jie; De Oliveira Vigier, Karine; Gu, Yanlong; Jérôme, François

    2015-01-01

    We show that the coating of choline chloride on silica-supported AlCl3 allows the dehydration of carbohydrates to successfully proceed in low boiling point organic solvents. The concept is based on the in situ formation of a deep eutectic liquid phase on the catalyst surface, thus facilitating the interaction between the solid catalyst and insoluble carbohydrate. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. 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

  7. 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.

  8. Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Yuki Kita

    Full Text Available BACKGROUND: Optimal treatment for nonalcoholic steatohepatitis (NASH has not yet been established, particularly for individuals without diabetes. We examined the effects of metformin, commonly used to treat patients with type 2 diabetes, on liver pathology in a non-diabetic NASH mouse model. METHODOLOGY/PRINCIPAL FINDINGS: Eight-week-old C57BL/6 mice were fed a methionine- and choline-deficient plus high fat (MCD+HF diet with or without 0.1% metformin for 8 weeks. Co-administration of metformin significantly decreased fasting plasma glucose levels, but did not affect glucose tolerance or peripheral insulin sensitivity. Metformin ameliorated MCD+HF diet-induced hepatic steatosis, inflammation, and fibrosis. Furthermore, metformin significantly reversed hepatic steatosis and inflammation when administered after the development of experimental NASH. CONCLUSIONS/SIGNIFICANCE: These histological changes were accompanied by reduced hepatic triglyceride content, suppressed hepatic stellate cell activation, and the downregulation of genes involved in fatty acid metabolism, inflammation, and fibrogenesis. Metformin prevented and reversed steatosis and inflammation of NASH in an experimental non-diabetic model without affecting peripheral insulin resistance.

  9. Designing the Reverse Supply Chain

    DEFF Research Database (Denmark)

    Gobbi, Chiara

    2011-01-01

    for the reverse supply chain. Design/methodology/approach – In order to identify the relevance of the Fisher model, the model needs to be recast in terms of PRV, which, in this context, is considered the independent variable in the reverse logistics arena. Products defined as innovative in Fisher's taxonomy....... Research limitations/implications – The focus is restricted to the industry of electrical and electronic products. Practical implications – Based on the outcome of the study, managers are able to determine the basic prerequisites for the design of their reverse supply chains. Originality/value – Previous......Purpose – The purpose of this paper is to explore the impact of the product residual value (PRV) and the loss of value over time of returned products in the reverse supply chain configuration. It also examines whether or not the distinction of Fisher's functional and innovative products holds...

  10. Towards a reversible functional language

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2012-01-01

    first-match policy for case expressions, we can write overlapping patterns in case branches, as is customary in ordinary functional languages, and also in leaf expressions, unlike existing inverse interpreter methods, which enables concise programs. In patterns, the use of a duplication....../equality operator also simplifies inverse computation and program inversion. We discuss the advantages of a reversible functional language using example programs, including run-length encoding. Program inversion is seen to be as lightweight as for imperative reversible languages and realized by recursive descent......We identify concepts of reversibility for a functional language by means of a set of semantic rules with specific properties. These properties include injectivity along with local backward determinism, an important operational property for an efficient reversible language. We define a concise...

  11. Global metabolic profile identifies choline kinase alpha as a key regulator of glutathione-dependent antioxidant cell defense in ovarian carcinoma.

    Science.gov (United States)

    Granata, Anna; Nicoletti, Roberta; Perego, Paola; Iorio, Egidio; Krishnamachary, Balaji; Benigni, Fabio; Ricci, Alessandro; Podo, Franca; Bhujwalla, Zaver M; Canevari, Silvana; Bagnoli, Marina; Mezzanzanica, Delia

    2015-05-10

    Epithelial Ovarian Cancer (EOC) "cholinic phenotype", characterized by increased intracellular phosphocholine content sustained by over-expression/activity of choline kinase-alpha (ChoKα/CHKA), is a metabolic cellular reprogramming involved in chemoresistance with still unknown mechanisms.By stable CHKA silencing and global metabolic profiling here we demonstrate that CHKA knockdown hampers growth capability of EOC cell lines both in vitro and in xenotransplant in vivo models. It also affected antioxidant cellular defenses, decreasing glutathione and cysteine content while increasing intracellular levels of reactive oxygen species, overall sensitizing EOC cells to current chemotherapeutic regimens. Natural recovering of ChoKα expression after its transient silencing rescued the wild-type phenotype, restoring intracellular glutathione content and drug resistance. Rescue and phenocopy of siCHKA-related effects were also obtained by artificial modulation of glutathione levels. The direct relationship among CHKA expression, glutathione intracellular content and drug sensitivity was overall demonstrated in six different EOC cell lines but notably, siCHKA did not affect growth capability, glutathione metabolism and/or drug sensitivity of non-tumoral immortalized ovarian cells. The "cholinic phenotype", by recapitulating EOC addiction to glutathione content for the maintenance of the antioxidant defense, can be therefore considered a unique feature of cancer cells and a suitable target to improve chemotherapeutics efficacy.

  12. (1)H HR-MAS spectroscopy for quantitative measurement of choline concentration in amniotic fluid as a marker of fetal lung maturity: inter- and intraobserver reproducibility study.

    Science.gov (United States)

    Joe, Bonnie N; Vahidi, Kiarash; Zektzer, Andrew; Chen, Mei-Hsiu; Clifton, Matthew S; Butler, Thomas; Keshari, Kayvan; Kurhanewicz, John; Coakley, Fergus; Swanson, Mark G

    2008-12-01

    To determine the intra- and interobserver reproducibility of human amniotic fluid metabolite concentration measurements (including potential markers of fetal lung maturity) detectable by MR spectroscopy. (1)H high-resolution magic angle spinning (HR-MAS) spectroscopy was performed at 11.7 T on 23 third-trimester amniotic fluid samples. Samples were analyzed quantitatively using 3-(trimethylsilyl)propionic-2,2,3,3-d(4) acid (TSP) as a reference. Four observers independently quantified eight metabolite regions (TSP, lactate doublet and quartet, alanine, citrate, creatinine, choline, and glucose) twice from anonymized, randomized spectra using a semiautomated software program. Excellent inter- and intraobserver reproducibility was found for all metabolites. Intraclass correlation as a measure of interobserver agreement for the four readers ranged from 0.654 to 0.995. A high correlation of 0.973 was seen for choline in particular, a major component of surfactant. Pearson correlation as a measure of intraobserver reproducibility ranged from 0.478 to 0.999. Quantification of choline and other metabolite concentrations in amniotic fluid by high-resolution MR spectroscopy can be performed with high inter- and intraobserver reproducibility. Demonstration of reproducible metabolite concentration measurements is a critical first step in the search for biomarkers of fetal lung maturity. (c) 2008 Wiley-Liss, Inc.

  13. Spontaneous direct and reverse osmosis

    International Nuclear Information System (INIS)

    Valitov, N.Kh.

    1996-01-01

    It has been ascertained experimentally that in the course of separation of CsCl, KCl, NaCl aqueous solutions by semi-permeable membrane from distilled water the direct and then reverse osmosis are observed. The same sequence is observed in case of separation of CsCl aqueous solutions from NaCl of different concentrations. The reason for the direct and reverse osmosis has been explained. 5 refs.; 3 figs. 1 tab

  14. Initiation of HIV Reverse Transcription

    OpenAIRE

    Isel, Catherine; Ehresmann, Chantal; Marquet, Roland

    2010-01-01

    Reverse transcription of retroviral genomes into double stranded DNA is a key event for viral replication. The very first stage of HIV reverse transcription, the initiation step, involves viral and cellular partners that are selectively packaged into the viral particle, leading to an RNA/protein complex with very specific structural and functional features, some of which being, in the case of HIV-1, linked to particular isolates. Recent understanding of the tight spatio-temporal regulation of...

  15. New splicing mutation in the choline kinase beta (CHKB) gene causing a muscular dystrophy detected by whole-exome sequencing.

    Science.gov (United States)

    Oliveira, Jorge; Negrão, Luís; Fineza, Isabel; Taipa, Ricardo; Melo-Pires, Manuel; Fortuna, Ana Maria; Gonçalves, Ana Rita; Froufe, Hugo; Egas, Conceição; Santos, Rosário; Sousa, Mário

    2015-06-01

    Muscular dystrophies (MDs) are a group of hereditary muscle disorders that include two particularly heterogeneous subgroups: limb-girdle MD and congenital MD, linked to 52 different genes (seven common to both subgroups). Massive parallel sequencing technology may avoid the usual stepwise gene-by-gene analysis. We report the whole-exome sequencing (WES) analysis of a patient with childhood-onset progressive MD, also presenting mental retardation and dilated cardiomyopathy. Conventional sequencing had excluded eight candidate genes. WES of the trio (patient and parents) was performed using the ion proton sequencing system. Data analysis resorted to filtering steps using the GEMINI software revealed a novel silent variant in the choline kinase beta (CHKB) gene. Inspection of sequence alignments ultimately identified the causal variant (CHKB:c.1031+3G>C). This splice site mutation was confirmed using Sanger sequencing and its effect was further evaluated with gene expression analysis. On reassessment of the muscle biopsy, typical abnormal mitochondrial oxidative changes were observed. Mutations in CHKB have been shown to cause phosphatidylcholine deficiency in myofibers, causing a rare form of CMD (only 21 patients reported). Notwithstanding interpretative difficulties that need to be overcome before the integration of WES in the diagnostic workflow, this work corroborates its utility in solving cases from highly heterogeneous groups of diseases, in which conventional diagnostic approaches fail to provide a definitive diagnosis.

  16. Effect of water presence on choline chloride-2urea ionic liquid and coating platings from the hydrated ionic liquid

    Science.gov (United States)

    Du, Cuiling; Zhao, Binyuan; Chen, Xiao-Bo; Birbilis, Nick; Yang, Haiyan

    2016-07-01

    In the present study, hygroscopicity of the choline chloride-urea (ChCl-2Urea) ionic liquid (IL) was confirmed through Karl-Fisher titration examination, indicating that the water content in the hydrated ChCl-2Urea IL was exposure-time dependent and could be tailored by simple heating treatment. The impact of the absorbed water on the properties of ChCl-2Urea IL, including viscosity, electrical conductivity, electrochemical window and chemical structure was investigated. The results show that water was able to dramatically reduce the viscosity and improve the conductivity, however, a broad electrochemical window could be persisted when the water content was below ~6 wt.%. These characteristics were beneficial for producing dense and compact coatings. Nickel (Ni) coatings plating from hydrated ChCl-2Urea IL, which was selected as an example to show the effect of water on the electroplating, displayed that a compact and corrosion-resistant Ni coating was plated from ChCl-2Urea IL containing 6 wt.% water doped with 400 mg/L NA at a moderate temperature. As verified by FTIR analysis, the intrinsic reason could be ascribed that water was likely linked with urea through strong hydrogen bond so that the water decomposition was suppressed during plating. Present study may provide a reference to prepare some similar water-stable ILs for plating.

  17. DETERMINATION OF CARBAMATE PESTICIDES USING A BIOSENSOR BASED ON ENZYME ACETYLCHOLINESTERASE AND CHOLIN OXIDASE ON PLATINUM ELECTRODE

    Directory of Open Access Journals (Sweden)

    Mashuni Mashuni

    2010-12-01

    Full Text Available In recent years, instead of their potential hazard to human health, carbamic pesticides are widely used in agriculture. Therefore, there is a growing interest in rapid and accurate determination for food safety and environmental monitoring. The aim of this research is to designs a biosensor for analyzing carbamate pesticides residue in sample with composite variables of glutaraldehyde (GA concentration in electrode membrane. Enzyme acetylcholinesterase (AChE was co-immobilised with choline oxidase (ChO onto a platinum (Pt surface using a solution of 5%, 10%, 15% cellulose acetate and 25% glutaraldehyde. The result of this research show that detection limit of the sensor using cellulose acetate 5%, 10 % and 15 % are 10-7.7 M, 10-8.7 M and 10-7.6 M respectively. The results are approximately equal to 2.2 ppb-0.2 ppb, which means that this biosensor is very sensitive for determining carbamates pesticides residue. Detection limit of biosensors are comparable to that of the conventional instrument such as Gas Chromatography (GC and High Pressure Liquid Chromatography (HPLC, i.e. 1.5 ppb and 2.0 ppb respectively. The proposed electrochemical pesticide sensitivity test exhibited high sensitivity, desirable accuracy, low cost and simplified procedure.

  18. The choline oxidase gene codA confers salt tolerance to transgenic Eucalyptus globulus in a semi-confined condition.

    Science.gov (United States)

    Yu, Xiang; Kikuchi, Akira; Matsunaga, Etsuko; Morishita, Yoshihiko; Nanto, Kazuya; Sakurai, Nozomu; Suzuki, Hideyuki; Shibata, Daisuke; Shimada, Teruhisa; Watanabe, Kazuo N

    2013-06-01

    The performance of tree species is influenced by environmental factors and growth stages. To evaluate the practical performance of transgenic tree species, it is insufficient to grow small, young trees under controlled conditions, such as in a growth chamber. Three transgenic Eucalyptus globulus lines, carrying the choline oxidase gene, were investigated for their salt tolerance and expression of the transgene at the young plantlet stage in a special netted-house. To clarify the characteristics at the young as well during the later stages, salt tolerance and the properties of the transgenic lines at large juvenile and adult stages were evaluated in the special netted-house. All transgenic lines showed high glycinebetaine content, particularly in young leaves. Trees of the transgenic line 107-1 showed low damage because of salinity stress based on the results from the chlorophyll analysis and malondialdehyde content, and they survived the high-salt-shock treatment at the large juvenile and adult stages. Only this line showed salt tolerance at all stages in the special netted-house. In this evaluation in the special netted-house, the tolerant line among young plantlets might perform better at all stages. Since evaluation in these special netted-house mimics field evaluation, line 107-1 is a potential tolerant line.

  19. 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.

  20. 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.

  1. 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.

  2. [Influence of feeding rumen-protected choline to transition dairy cows. Part 1: metabolism and milk yield].

    Science.gov (United States)

    Furken, C; Hoedemaker, M

    2014-01-01

    The effects of rumen-protected choline (RPC) on energy metabolism and milk production in dairy cows were analyzed. Two hundred and ninety-eight primiparous and multiparous cows of a high producing dairy herd (mean daily milk yield: 32 l) were randomly assigned to control or treatment groups and were fed with 0 or 15 g RPC, respectively, (corresponding to 0 and 60 g/d ReaShure®, respectively) from 21 days before expected calving to 21 days postpartum (p. p.). Blood metabolites were determined for either all cows (glucose, β-hydroxybutyrate [BHB]) or randomly (insulin, insulin-like growth factor-1 [IGF-1], non-esterified fatty acids [NEFA]) during the periparturient period. An index for insulin sensitivity (RQUICKI) was calculated and milk production data (dairy herd improvement tests, 100-days-, 305-days-, milk peak yield, colostrum quality) was analyzed. In the statistical analysis, a distinction was made between the feeding groups and between the parity, and their interactions were analyzed. With the exception of a lower 305-day-milk yield in the treatment group (p cows had less cases of subclinical ketosis a. p. and p. p. (OR a. p.: 0.178; OR p. p.: 0.310), more of them were above the threshold for somatic cell counts (OR 2.584-3.298), and their milk yields were higher (p metabolism or the milk production in this herd. Further research in other dairy herds should focus on this topic.

  3. Proton MR Spectroscopy: Higher Right Anterior Cingulate N-Acetylaspartate/Choline Ratio in Asperger Syndrome Compared with Healthy Controls

    Science.gov (United States)

    Oner, O.; Devrimci-Ozguven, H.; Oktem, F.; Yagmurlu, B.; Baskak, B.; Munir, K.M.

    2011-01-01

    BACKGROUND AND PURPOSE One former study reported higher prefrontal N-acetylaspartate (NAA) levels in patients with Asperger syndrome (AS). The objective of the current study was to test the hypothesis that patients with AS would have higher dorsolateral prefrontal and anterior cingulate cortex NAA/creatine (Cr) and that NAA/Cr would be correlated with symptom severity. MATERIALS AND METHODS NAA/choline (Cho), NAA/Cr, and Cho/Cr values revealed by 1H-MR spectroscopy in 14 right-handed male patients with AS (6 medicated with risperidone), 17–38 years of age, diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were compared with those of 21 right-handed male controls frequency-matched by age and intelligence quotient scores. RESULTS Patients with AS had significantly higher anterior cingulate NAA/Cho levels (z = –2.18, P = .028); there was a statistical trend for higher anterior cingulate NAA/Cr (z = –1.81, P = .069) that was significant when only the unmedicated patients with AS were taken into account (z = –1.95, P = .050). There were no significant differences in dorsolateral prefrontal MR spectroscopy values. CONCLUSIONS Our findings show that individuals with AS had higher NAA/Cho levels in the right anterior cingulate compared with healthy controls and that higher anterior cingulate NAA/Cho levels were correlated with higher Yale-Brown Obsessive Compulsive Scale total scores. PMID:17846198

  4. Reversal of idiopathic hypogonadotropic hypogonadism.

    Science.gov (United States)

    Raivio, Taneli; Falardeau, John; Dwyer, Andrew; Quinton, Richard; Hayes, Frances J; Hughes, Virginia A; Cole, Lindsay W; Pearce, Simon H; Lee, Hang; Boepple, Paul; Crowley, William F; Pitteloud, Nelly

    2007-08-30

    Idiopathic hypogonadotropic hypogonadism, which may be associated with anosmia (the Kallmann syndrome) or with a normal sense of smell, is a treatable form of male infertility caused by a congenital defect in the secretion or action of gonadotropin-releasing hormone (GnRH). Patients have absent or incomplete sexual maturation by the age of 18. Idiopathic hypogonadotropic hypogonadism was previously thought to require lifelong therapy. We describe 15 men in whom reversal of idiopathic hypogonadotropic hypogonadism was sustained after discontinuation of hormonal therapy. We defined the sustained reversal of idiopathic hypogonadotropic hypogonadism as the presence of normal adult testosterone levels after hormonal therapy was discontinued. Ten sustained reversals were identified retrospectively. Five sustained reversals were identified prospectively among 50 men with idiopathic hypogonadotropic hypogonadism after a mean (+/-SD) duration of treatment interruption of 6+/-3 weeks. Of the 15 men who had a sustained reversal, 4 had anosmia. At initial evaluation, 6 men had absent puberty, 9 had partial puberty, and all had abnormal secretion of GnRH-induced luteinizing hormone. All 15 men had received previous hormonal therapy to induce virilization, fertility, or both. Among those whose hypogonadism was reversed, the mean serum level of endogenous testosterone increased from 55+/-29 ng per deciliter (1.9+/-1.0 nmol per liter) to 386+/-91 ng per deciliter (13.4+/-3.2 nmol per liter, Phypogonadotropic hypogonadism and the Kallmann syndrome was noted after discontinuation of treatment in about 10% of patients with either absent or partial puberty. Therefore, brief discontinuation of hormonal therapy to assess reversibility of hypogonadotropic hypogonadism is reasonable. (ClinicalTrials.gov number, NCT00392756 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.

  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 (11)C-choline for evaluation of prostate cancer patients with biochemical recurrence: meta-analysis and critical review of available data.

    Science.gov (United States)

    Fanti, Stefano; Minozzi, Silvia; Castellucci, Paolo; Balduzzi, Sara; Herrmann, Ken; Krause, Bernd Joachim; Oyen, Wim; Chiti, Arturo

    2016-01-01

    For the last decade PET and PET/CT with (11)C-choline have been proposed for the evaluation of prostate cancer (PC), but the diagnostic performance of (11)C-choline PET/CT is still a matter of debate. We performed a comprehensive review of the most important clinical application of (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 (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

  7. 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

  8. Reverse hybrid total hip arthroplasty

    Science.gov (United States)

    Wangen, Helge; Havelin, Leif I; Fenstad, Anne M; Hallan, Geir; Furnes, Ove; Pedersen, Alma B; Overgaard, Søren; Kärrholm, Johan; Garellick, Göran; Mäkelä, Keijo; Eskelinen, Antti; Nordsletten, Lars

    2017-01-01

    Background and purpose The use of a cemented cup together with an uncemented stem in total hip arthroplasty (THA) has become popular in Norway and Sweden during the last decade. The results of this prosthetic concept, reverse hybrid THA, have been sparsely described. The Nordic Arthroplasty Register Association (NARA) has already published 2 papers describing results of reverse hybrid THAs in different age groups. Based on data collected over 2 additional years, we wanted to perform in depth analyses of not only the reverse hybrid concept but also of the different cup/stem combinations used. Patients and methods From the NARA, we extracted data on reverse hybrid THAs from January 1, 2000 until December 31, 2013. 38,415 such hips were studied and compared with cemented THAs. The Kaplan-Meier method and Cox regression analyses were used to estimate the prosthesis survival and the relative risk of revision. The main endpoint was revision for any reason. We also performed specific analyses regarding the different reasons for revision and analyses regarding the cup/stem combinations used in more than 500 cases. Results We found a higher rate of revision for reverse hybrids than for cemented THAs, with an adjusted relative risk of revision (RR) of 1.4 (95% CI: 1.3–1.5). At 10 years, the survival rate was 94% (CI: 94–95) for cemented THAs and 92% (95% CI: 92–93) for reverse hybrids. The results for the reverse hybrid THAs were inferior to those for cemented THAs in patients aged 55 years or more (RR =1.1, CI: 1.0–1.3; p revision due to periprosthetic femoral fracture for reverse hybrids than for cemented THAs in patients aged 55 years or more (RR =3.1, CI: 2.2–4.5; p revision than cemented THAs in patients aged 55 or more. The difference in survival was mainly caused by a higher incidence of early revision due to periprosthetic femoral fracture in the reversed hybrid THAs. PMID:28095724

  9. Vasectomy reversal: a clinical update

    Directory of Open Access Journals (Sweden)

    Abhishek P Patel

    2016-01-01

    Full Text Available Vasectomy is a safe and effective method of contraception used by 42-60 million men worldwide. Approximately 3%-6% of men opt for a vasectomy reversal due to the death of a child or divorce and remarriage, change in financial situation, desire for more children within the same marriage, or to alleviate the dreaded postvasectomy pain syndrome. Unlike vasectomy, vasectomy reversal is a much more technically challenging procedure that is performed only by a minority of urologists and places a larger financial strain on the patient since it is usually not covered by insurance. Interest in this procedure has increased since the operating microscope became available in the 1970s, which consequently led to improved patency and pregnancy rates following the procedure. In this clinical update, we discuss patient evaluation, variables that may influence reversal success rates, factors to consider in choosing to perform vasovasostomy versus vasoepididymostomy, and the usefulness of vasectomy reversal to alleviate postvasectomy pain syndrome. We also review the use of robotics for vasectomy reversal and other novel techniques and instrumentation that have emerged in recent years to aid in the success of this surgery.

  10. Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour.

    Science.gov (United States)

    Paternain, Laura; Martisova, Eva; Campión, Javier; Martínez, J Alfredo; Ramírez, Maria J; Milagro, Fermin I

    2016-02-15

    Adverse early life events are associated with altered stress responsiveness and metabolic disturbances in the adult life. Dietary methyl donor supplementation could be able to reverse the negative effects of maternal separation by affecting DNA methylation in the brain. In this study, maternal separation during lactation reduced body weight gain in the female adult offspring without affecting food intake, and altered total and HDL-cholesterol levels. Also, maternal separation induced a cognitive deficit as measured by NORT and an increase in the immobility time in the Porsolt forced swimming test, consistent with increased depression-like behaviour. An 18-week dietary supplementation with methyl donors (choline, betaine, folate and vitamin B12) from postnatal day 60 also reduced body weight without affecting food intake. Some of the deleterious effects induced by maternal separation, such as the abnormal levels of total and HDL-cholesterol, but especially the depression-like behaviour as measured by the Porsolt test, were reversed by methyl donor supplementation. Also, the administration of methyl donors increased total DNA methylation (measured by immunohistochemistry) and affected the expression of insulin receptor in the hippocampus of the adult offspring. However, no changes were observed in the DNA methylation status of insulin receptor and corticotropin-releasing hormone (CRH) promoter regions in the hypothalamus. In summary, methyl donor supplementation reversed some of the deleterious effects of an early life-induced model of depression in rats and altered the DNA methylation profile in the brain. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Reverse Knowledge Transfer in MNEs

    DEFF Research Database (Denmark)

    Mudambi, Ram; Piscitello, Lucia; Rabbiosi, Larissa

    2014-01-01

    It is now well recognized that multinational enterprises (MNEs) are differentiated networks wherein subsidiaries vary in terms of their ability to create new knowledge and competencies for their parent groups. In much of this theory, it is taken for granted that subsidiary innovativeness has...... a positive correlation with the extent of reverse knowledge transfers to the parent MNE. Relying on the headquarters-subsidiary view of the MNE, we argue that, beyond a point, increasing subsidiary innovativeness will be associated with lower reverse knowledge transfers. Further, we argue...... that this relationship is sensitive to the subsidiary entry mode. Using data from a sample of 293 Italian subsidiaries, we find strong support for our hypotheses. In particular, our results confirm that the effect of subsidiary innovativeness on reverse knowledge transfers displays an inverted-U shape...

  12. Reverse innovation in maternal health.

    Science.gov (United States)

    Firoz, Tabassum; Makanga, Prestige Tatenda; Nathan, Hannah L; Payne, Beth; Magee, Laura A

    2017-09-01

    Reverse innovation, defined as the flow of ideas from low- to high-income settings, is gaining traction in healthcare. With an increasing focus on value, investing in low-cost but effective and innovative solutions can be of mutual benefit to both high- and low-income countries. Reverse innovation has a role in addressing maternal health challenges in high-income countries by harnessing these innovative solutions for vulnerable populations especially in rural and remote regions. In this paper, we present three examples of 'reverse innovation' for maternal health: a low-cost, easy-to-use blood pressure device (CRADLE), a diagnostic algorithm (mini PIERS) and accompanying mobile app (PIERS on the Move), and a novel method for mapping maternal outcomes (MOM).

  13. Reverse genetics with animal viruses. NSV reverse genetics

    International Nuclear Information System (INIS)

    Mebatsion, T.

    2005-01-01

    New strategies to genetically manipulate the genomes of several important animal pathogens have been established in recent years. This article focuses on the reverse genetics techniques, which enables genetic manipulation of the genomes of non-segmented negative-sense RNA viruses. Recovery of a negative-sense RNA virus entirely from cDNA was first achieved for rabies virus in 1994. Since then, reverse genetic systems have been established for several pathogens of medical and veterinary importance. Based on the reverse genetics technique, it is now possible to design safe and more effective live attenuated vaccines against important viral agents. In addition, genetically tagged recombinant viruses can be designed to facilitate serological differentiation of vaccinated animals from infected animals. The approach of delivering protective immunogens of different pathogens using a single vector was made possible with the introduction of the reverse genetics system, and these novel broad-spectrum vaccine vectors have potential applications in improving animal health in developing countries. (author)

  14. Reverse Zymography: Overview and Pitfalls.

    Science.gov (United States)

    Sharma, Kanika; Bhattacharyya, Debasish

    2017-01-01

    Reverse zymography is a technique by which protease inhibitor(s) in a sample could be electrophoretically separated in a substrate-impregnated acrylamide gel and their relative abundance could be semi-quantified. The gel after electrophoresis is incubated with a protease when the impregnated substrate and all other proteins of the sample are degraded into small peptides except the inhibitor(s) that show clear bands against a white background. Since reverse zymography cannot distinguish between a protease inhibitor and a protein that is resistant against proteolysis, the results should be confirmed from inhibition of protease activity by solution state assay.

  15. Marburg Virus Reverse Genetics Systems

    Directory of Open Access Journals (Sweden)

    Kristina Maria Schmidt

    2016-06-01

    Full Text Available The highly pathogenic Marburg virus (MARV is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems.

  16. Environmental exposure to lead induces oxidative stress and modulates the function of the antioxidant defense system and the immune system in the semen of males with normal semen profile

    Energy Technology Data Exchange (ETDEWEB)

    Kasperczyk, Aleksandra; Dobrakowski, Michał [Dept. of Biochemistry, School of Medicine with the Division of Dentistry, Medical University of Silesia, Katowice, Jordana 19, 41-808 Zabrze (Poland); Czuba, Zenon P. [Dept. of Microbiology and Immunology, School of Medicine with the Division of Dentistry, Medical University of Silesia, Katowice, Jordana 19, 41-808 Zabrze (Poland); Horak, Stanisław [I-st Chair and Clin. Dept. of Gynecology, Obstetrics and Gynecological Oncology, School of Medicine with the Division of Dentistry, Medical University of Silesia, Katowice, Batorego 15, 41-902 Bytom (Poland); Kasperczyk, Sławomir, E-mail: kaslav@mp.pl [Dept. of Biochemistry, School of Medicine with the Division of Dentistry, Medical University of Silesia, Katowice, Jordana 19, 41-808 Zabrze (Poland)

    2015-05-01

    We investigated the associations between environmental exposure to lead and a repertoire of cytokines in seminal plasma of males with normal semen profile according to the WHO criteria. Based on the median lead concentration in seminal plasma, 65 samples were divided into two groups: low (LE) and high exposure to lead (HE). Differences in semen volume and the pH, count, motility and morphology of sperm cells were not observed between the examined groups. The total oxidant status value and the level of protein sulfhydryl groups as well as the activities of manganese superoxide dismutase and catalase were significantly higher in the HE group, whereas the total antioxidant capacity value and the activities of glutathione reductase and glutathione-S-transferase were depressed. IL-7, IL-10, IL-12, and TNF-α levels were significantly higher in the HE group compared with the LE group. Environmental exposure to lead is sufficient to induce oxidative stress in seminal plasma and to modulate antioxidant defense system. - Highlights: • Lead induces oxidative stress in seminal plasma in human. • Lead modulates antioxidant defense system in seminal plasma in human. • Lead does not change a Th1/Th2 imbalance in seminal plasma in human.

  17. Preclinical test: bacterial reverse mutation test for 18F-fluorocholine produced in CDTN

    International Nuclear Information System (INIS)

    Mendes, Bruno M.; Bispo, Ana Carolina A.; Campos, Danielle C.; Silva, Juliana B.

    2013-01-01

    The choline labeled with fluorine-18 (18FCH) is being considered as a great importance radiopharmaceutical due to its effective detection of many type of malignant neoplasm. The research related to 18 F-fluorocholine synthesis in CDTN was initiated in 2010. In order to obtain clinical research approval, as well as to register 18 FCH for marketing, safety and efficacy preclinical testing are required. The present work evaluated the 18 FCH genotoxic potential through the bacterial reverse mutation test (Ames test) using Salmonella typhimurium TA-98, TA-100, TA-1535 and TA-1537 strains and Escherichia coli WP2 uvrA strain. The reverse mutation test in bacteria for fluorcolina was conducted in two stages. Initially the method was applied to 'cold' fluorocholine molecule (19FCH). Subsequently, the decayed product of 18 FCH synthesis was evaluated. The first step was performed in order to examine the FCH molecule mutagenicity. The second was carried out to determine the mutagenic potential of final product. All strains were tested in triplicate for each exposure concentration, in the presence and absence of metabolic activation (S-9 mix - 10%). There were no statistically significant increases in revertant colonies rate for any strains tested after their exposure to decayed 18 FCH or 19 FCH. The number of revertant colonies in positive controls was significantly higher than that observed in significant increases in revertant colonies rate for any strains tested after their exposure to decayed 18 FCH or 19 FCH. The number of revertant colonies in positive controls was significantly higher than that observed in negative controls. Based on results of this assay, 18 FCH and 19 FCH, at tested doses, were found to be non-mutagenic in bacterial reverse mutation test. (author)

  18. 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.

  19. Adult ciliary neurotrophic factor receptors help maintain facial motor neuron choline acetyltransferase expression in vivo following nerve crush.

    Science.gov (United States)

    Lee, Nancy; Rydyznski, Carolyn E; Rasch, Matthew S; Trinh, Dennis S; MacLennan, A John

    2017-04-01

    Exogenous ciliary neurotrophic factor (CNTF) administration promotes the survival of motor neurons in a wide range of models. It also increases the expression of the critical neurotransmitter enzyme choline acetyltransferase (ChAT) by in vitro motor neurons, likely independent of its effects on their survival. We have used the adult mouse facial nerve crush model and adult-onset conditional disruption of the CNTF receptor α (CNTFRα) gene to directly examine the in vivo roles played by endogenous CNTF receptors in adult motor neuron survival and ChAT maintenance, independent of developmental functions. We have previously shown that adult activation of the CreER gene construct in floxed CNTFRα mice depletes this essential receptor subunit in a large subset of motor neurons (and all skeletal muscle, as shown in this study) but has no effect on the survival of intact or lesioned motor neurons, indicating that these adult CNTF receptors play no essential survival role in this model, in contrast to their essential role during embryonic development. Here we show that this same CNTFRα depletion does not affect ChAT labeling in nonlesioned motor neurons, but it significantly increases the loss of ChAT following nerve crush. The data suggest that, although neither motor neuron nor muscle CNTF receptors play a significant, nonredundant role in the maintenance of ChAT in intact adult motor neurons, the receptors become essential for ChAT maintenance when the motor neurons are challenged by nerve crush. Therefore, the data suggest that the receptors act as a critical component of an endogenous neuroprotective mechanism. J. Comp. Neurol. 525:1206-1215, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Localization of choline acetyltransferase and tyrosine hydroxylase immunoreactivities in the superior colliculus of the microbat,Rhinolophus ferrumequinum.

    Science.gov (United States)

    Jeong, Se-Jin; Jeon, Chang-Jin

    2017-06-01

    The purpose of this study was to determine whether the superior colliculus (SC) of the microbat has the same neurochemical makeup as that of other mammals. We examined the organization of choline acetyltransferase (ChAT)- and tyrosine hydroxylase-immunoreactive (TH-IR) fibers/cells using standard immunohistochemistry with antibodies against ChAT and TH. ChAT-IR fibers observed in the superficial layers were denser than those in the deeper layers, and these fibers were classified into two types: small varicose fibers and large varicose fibers. ChAT-IR cells were predominantly located in the superficial layers with diverse morphologies. Among the well-known sources of cholinergic fibers in the mammalian SC, pedunculopontine tegmental nucleus (PPTN) and laterodorsal tegmental nucleus (LDTN) contained strongly labeled ChAT-IR cells, while no cholinergic structures were found in the parabigeminal nucleus (PBG) in the microbat brain. TH-immunoreactivity was found within fibers but not within cells. The density of TH-IR fibers was high in the zonal layer, moderate in the superficial gray and optic layers, and low in the deeper layers. Well-labeled TH-IR cells were also observed within area 13 and the locus coeruleus, known as the sources of catecholaminergic fibers in other mammalian SC. Although there are some cytoarchitectural variations among species, our results clearly showed elaborately organized ChAT-IR and TH-IR fibers/cells in the microbat SC. Our findings will contribute significantly to the understanding of actively constructed microbat visual systems.

  1. 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.

  2. Effect of oral intake of choline-stabilized orthosilicic acid on skin, nails and hair in women with photodamaged skin.

    Science.gov (United States)

    Barel, A; Calomme, M; Timchenko, A; De Paepe, K; Paepe, K De; Demeester, N; Rogiers, V; Clarys, P; Vanden Berghe, D

    2005-10-01

    Chronic exposure of the skin to sunlight causes damage to the underlying connective tissue with a loss of elasticity and firmness. Silicon (Si) was suggested to have an important function in the formation and maintenance of connective tissue. Choline-stabilized orthosilicic acid ("ch-OSA") is a bioavailable form of silicon which was found to increase the hydroxyproline concentration in the dermis of animals. The effect of ch-OSA on skin, nails and hair was investigated in a randomized, double blind, placebo-controlled study. Fifty women with photodamaged facial skin were administered orally during 20 weeks, 10 mg Si/day in the form of ch-OSA pellets (n=25) or a placebo (n=25). Noninvasive methods were used to evaluate skin microrelief (forearm), hydration (forearm) and mechanical anisotropy (forehead). Volunteers evaluated on a virtual analog scale (VAS, "none=0, severe=3") brittleness of hair and nails. The serum Si concentration was significantly higher after a 20-week supplementation in subjects with ch-OSA compared to the placebo group. Skin roughness parameters increased in the placebo group (Rt:+8%; Rm: +11%; Rz: +6%) but decreased in the ch-OSA group (Rt: -16%; Rm: -19%; Rz: -8%). The change in roughness from baseline was significantly different between ch-OSA and placebo groups for Rt and Rm. The difference in longitudinal and lateral shear propagation time increased after 20 weeks in the placebo group but decreased in the ch-OSA group suggesting improvement in isotropy of the skin. VAS scores for nail and hair brittleness were significantly lower after 20 weeks in the ch-OSA group compared to baseline scores. Oral intake of ch-OSA during the 20 weeks results in a significant positive effect on skin surface and skin mechanical properties, and on brittleness of hair and nails.

  3. 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.

  4. 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

  5. Reverse hybrid total hip arthroplasty

    DEFF Research Database (Denmark)

    Wangen, Helge; Havelin, Leif I.; Fenstad, Anne M

    2017-01-01

    . Patients and methods - From the NARA, we extracted data on reverse hybrid THAs from January 1, 2000 until December 31, 2013. 38,415 such hips were studied and compared with cemented THAs. The Kaplan-Meier method and Cox regression analyses were used to estimate the prosthesis survival and the relative risk...

  6. Reversibility of chronic airflow obstruction

    NARCIS (Netherlands)

    Postma, Dirkje Sjoukje

    1984-01-01

    This thesis deals with variations in airway diameter in patients with chronic, partly reversible airflow obstruction. The patients studied in this thesis have been addressed in the literature with terms as CAO, COPD, CNSLD. The confusion caused by combining patients in one descriptive term, e.g.

  7. CAPSULE REPORT: REVERSE OSMOSIS PROCESS

    Science.gov (United States)

    A failure analysis has been completed for the reverse osmosis (RO) process. The focus was on process failures that result in releases of liquids and vapors to the environment. The report includes the following: 1) A description of RO and coverage of the principles behind the proc...

  8. Reversible colour change in Arthropoda.

    Science.gov (United States)

    Umbers, Kate D L; Fabricant, Scott A; Gawryszewski, Felipe M; Seago, Ainsley E; Herberstein, Marie E

    2014-11-01

    The mechanisms and functions of reversible colour change in arthropods are highly diverse despite, or perhaps due to, the presence of an exoskeleton. Physiological colour changes, which have been recorded in 90 arthropod species, are rapid and are the result of changes in the positioning of microstructures or pigments, or in the refractive index of layers in the integument. By contrast, morphological colour changes, documented in 31 species, involve the anabolism or catabolism of components (e.g. pigments) directly related to the observable colour. In this review we highlight the diversity of mechanisms by which reversible colour change occurs and the evolutionary context and diversity of arthropod taxa in which it has been observed. Further, we discuss the functions of reversible colour change so far proposed, review the limited behavioural and ecological data, and argue that the field requires phylogenetically controlled approaches to understanding the evolution of reversible colour change. Finally, we encourage biologists to explore new model systems for colour change and to engage scientists from other disciplines; continued cross-disciplinary collaboration is the most promising approach to this nexus of biology, physics, and chemistry. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

  9. 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

  10. 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

  11. 18O-Tracer Metabolomics Reveals Protein Turnover and CDP-Choline Cycle Activity in Differentiating 3T3-L1 Pre-Adipocytes.

    Directory of Open Access Journals (Sweden)

    Jay S Kirkwood

    Full Text Available The differentiation of precursor cells into mature adipocytes (adipogenesis has been an area of increased focus, spurred by a rise in obesity rates. Though our understanding of adipogenesis and its regulation at the cellular level is growing, many questions remain, especially regarding the regulation of the metabolome. The 3T3-L1 cell line is the most well characterized cellular model of adipogenesis. Using a time course metabolomics approach, we show that the 3T3-L1 preadipocyte metabolome is greatly altered during the first 48 hours of differentiation, where cells go through about two rounds of cell division, a process known as mitotic clonal expansion. Short-chain peptides were among several small molecules that were increased during mitotic clonal expansion. Additional indicators of protein turnover were also increased, including bilirubin, a degradation product of heme-containing proteins, and 3-methylhistidine, a post-translationally modified amino acid that is not reutilized for protein synthesis. To study the origin of the peptides, we treated differentiating preadipocytes with 18O labeled water and found that 18O was incorporated into the short chain peptides, confirming them, at least in part, as products of hydrolysis. Inhibitors of the proteasome or matrix metalloproteinases affected the peptide levels during differentiation, but inhibitors of autophagy or peptidases did not. 18O was also incorporated into several choline metabolites including cytidine 5'-diphosphocholine (CDP-choline, glycerophosphocholine, and several phosphatidylcholine species, indicative of phosphatidylcholine synthesis/degradation and of flux through the CDP-choline cycle, a hallmark of proliferating cells. 18O-Tracer metabolomics further showed metabolic labeling of glutamate, suggestive of glutaminolysis, also characteristic of proliferating cells. Together, these results highlight the utility of 18O isotope labeling in combination with metabolomics to

  12. 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.

  13. 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.)

  14. 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

  15. Role of 18F-Choline PET/CT in guiding biopsy in patients with risen PSA levels and previous negative biopsy for prostate cancer.

    Science.gov (United States)

    Jiménez Londoño, G A; García Vicente, A M; Amo-Salas, M; Fúnez Mayorga, F; López Guerrero, M A; Talavera Rubio, M P; Gutierrez Martin, P; González García, B; de la Torre Pérez, J A; Soriano Castrejón, Á M

    To study 18 F-Choline PET/CT in the diagnosis and biopsy guide of prostate cancer (pCa) in patients with persistently high prostate-specific antigen (PSA) and previous negative prostate biopsy. To compare the clinical risk factors and metabolic variables as predictors of malignancy. Patients with persistently elevated PSA in serum (total PSA >4ng/mL) and at least a previous negative or inconclusive biopsy were consecutively referred for a whole body 18 F-Choline PET/CT. Patient age, PSA level, PSA doubling time (PSAdt) and PSA velocity (PSAvel) were obtained. PET images were visually (positive or negative) and semiquantitatively (SUVmax) reviewed. 18 F-Choline uptake prostate patterns were defined as focal, multifocal, homogeneous or heterogeneous. Histology on biopsy using transrectal ultrasound-guided approach was the gold standard. Sensitivity (Se), specificity (Sp) and accuracy (Ac) of PET/CT for diagnosis of pCa were evaluated using per-patient and per-prostate lobe analysis. Receiver-operating-characteristic (ROC) curve analysis was used to assess the value of SUVmax to diagnose pCa. Correlation between PET/CT and biopsy results per-prostate lobe was assessed using the Chi-square test. Univariate and multivariate logistic regression analysis were applied to compare clinical risk factors and metabolic variables as predictors of malignancy. Thirty-six out of 43 patients with histologic confirmation were included. In 11 (30.5%) patients, pCa was diagnosed (Gleason score from 4 to 9). The mean values of patient age, PSA level, PSAdt and PSAvel were: 65.5 years, 15.6ng/ml, 28.1 months and 8.5ng/mL per year, respectively. Thirty-three patients had a positive PET/CT; 18 had a focal pattern, 7 multifocal, 4 homogeneous and 4 heterogeneous. Se, Sp and Ac of PET/CT were of 100%, 12% and 38% in the patient based analysis, and 87%, 29% and 14% in the prostate lobe based analysis, respectively. The ROC curve analysis of SUVmax showed an AUC of 0.568 (p=0.52). On a lobe

  16. 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.

  17. 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...... were studied serially in the acute phase, 1 week after, and 2-4 weeks after the onset of clinical symptoms. Ten healthy volunteers served as controls. A stimulated echo (STEAM) sequence was used for measurement of the brain metabolites in a volume of interest located within the infarcted area...

  18. EFFECT OF CHOLINE-STABILIZED ORTHOSILICIC ACID ON SYMPTOMS OF KNEE OSTEOARTHRITIS IN A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

    OpenAIRE

    GEUSENS, Piet; Pavelka, K.; Rovensky, J.; VANHOOF, Johan; Vanden Berghe, D.

    2014-01-01

    Background Choline-stabilized orthosilicic acid (ch-OSA) was previously found to stimulate bone collagen formation in osteopenic women (1). Objectives The aim of the present study was to evaluate the effect of ch-OSA on symptoms of knee osteoarthritis (OA) in a multicenter, randomized, double-blind, placebo-controlled, single joint study. Methods Over 12 weeks, 166 patients with documented knee OA (K&L grade II and III) and a baseline knee pain score of moderate or moderately severe o...

  19. A 12-week randomized, double-blind, placebo-controlled multicenter study of choline-stabilized orthosilicic acid in patients with symptomatic knee osteoarthritis

    OpenAIRE

    Geusens, Piet; Pavelka, Karel; Rovensky, Jozef; Vanhoof, Johan; Demeester, Nathalie; Calomme, Mario; Vanden Berghe, Dirk

    2017-01-01

    Background The aim of this study was to assess the efficacy of choline-stabilized orthosilicic acid (ch-OSA) in patients with symptomatic knee osteoarthritis (OA). Methods In a multicenter, double-blind, placebo-controlled study, 211 patients with knee OA (Kellgren and Lawrence grade II or III) and moderate to moderately severe pain were randomly allocated to ch-OSA or placebo for 12?weeks. The primary outcome was the change in the WOMAC pain subscale from baseline to week 12. Secondary outco...

  20. 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

    AIM: To study liver cell apoptosis caused by the toxicity of selenium and observe the alteration of choline compounds using in vitro 9.4T high resolution magnetic resonance spectroscopy. METHODS: Twenty male Wistar rats were randomly divided into two groups. The rats in the treatment group were...... intraperitoneally injected with sodium selenite and the control group with distilled water. All rats were sacrificed and the livers were dissected. (1)H-MRS data were collected using in vitro 9.4T high resolution magnetic resonance spectrometer. Spectra were processed using XWINNMR and MestRe-c 4.3. HE and TUNEL...

  1. Reversion phenomena of Cu-Cr alloys

    Science.gov (United States)

    Nishikawa, S.; Nagata, K.; Kobayashi, S.

    1985-01-01

    Cu-Cr alloys which were given various aging and reversion treatments were investigated in terms of electrical resistivity and hardness. Transmission electron microscopy was one technique employed. Some results obtained are as follows: the increment of electrical resistivity after the reversion at a constant temperature decreases as the aging temperature rises. In a constant aging condition, the increment of electrical resistivity after the reversion increases, and the time required for a maximum reversion becomes shorter as the reversion temperature rises. The reversion phenomena can be repeated, but its amount decreases rapidly by repetition. At first, the amount of reversion increases with aging time and reaches its maximum, and then tends to decrease again. Hardness changes by the reversion are very small, but the hardness tends to soften slightly. Any changes in transmission electron micrographs by the reversion treatment cannot be detected.

  2. Reversal agents in anaesthesia and critical care

    Directory of Open Access Journals (Sweden)

    Nibedita Pani

    2015-01-01

    Full Text Available Despite the advent of short and ultra-short acting drugs, an in-depth knowledge of the reversal agents used is a necessity for any anaesthesiologist. Reversal agents are defined as any drug used to reverse the effects of anaesthetics, narcotics or potentially toxic agents. The controversy on the routine reversal of neuromuscular blockade still exists. The advent of newer reversal agents like sugammadex have made the use of steroidal neuromuscular blockers like rocuronium feasible in rapid sequence induction situations. We made a review of the older reversal agents and those still under investigation for drugs that are regularly used in our anaesthesia practice.

  3. Laparoscopic reversal of Hartmann's procedure

    DEFF Research Database (Denmark)

    Svenningsen, Peter Olsen; Bulut, Orhan; Jess, Per

    2010-01-01

    %). There was no difference in postoperative complications between the two groups (10 versus 14%), and no anastomotic leaks. The total mortality was 2% as one patient died postoperatively after an open operation. CONCLUSION: It is possible for trained laparoscopic colorectal surgeons to perform laparoscopic reversal...... of all patients who underwent reversal of a colostomy after a primary Hartmann's procedure during the period May 2005 to December 2008 were reviewed retrospectively in a case-control study. RESULTS: A total of 43 patients were included. Twenty-one had a laparoscopic and 22 an open procedure. The two...... groups matched with regard to age, sex, American Society of Anestheologists (ASA) score, body mass index and indication for Hartmann's operation. A significantly longer operation time was found for laparoscopic than for open surgery (median 285 versus 158 minutes, p

  4. Reverse osmosis water purification system

    Science.gov (United States)

    Ahlstrom, H. G.; Hames, P. S.; Menninger, F. J.

    1986-01-01

    A reverse osmosis water purification system, which uses a programmable controller (PC) as the control system, was designed and built to maintain the cleanliness and level of water for various systems of a 64-m antenna. The installation operates with other equipment of the antenna at the Goldstone Deep Space Communication Complex. The reverse osmosis system was designed to be fully automatic; with the PC, many complex sequential and timed logic networks were easily implemented and are modified. The PC monitors water levels, pressures, flows, control panel requests, and set points on analog meters; with this information various processes are initiated, monitored, modified, halted, or eliminated as required by the equipment being supplied pure water.

  5. Laparoscopic reversal of Hartmann's procedure

    DEFF Research Database (Denmark)

    Svenningsen, Peter Olsen; Bulut, Orhan; Jess, Per

    2010-01-01

    INTRODUCTION: A change in procedure from open to laparoscopic reversal of Hartmann's colostomy was implemented at our department between May 2005 and December 2008. The aim of the study was to investigate if this change was beneficial for the patients. MATERIAL AND METHODS: The medical records...... of all patients who underwent reversal of a colostomy after a primary Hartmann's procedure during the period May 2005 to December 2008 were reviewed retrospectively in a case-control study. RESULTS: A total of 43 patients were included. Twenty-one had a laparoscopic and 22 an open procedure. The two...... groups matched with regard to age, sex, American Society of Anestheologists (ASA) score, body mass index and indication for Hartmann's operation. A significantly longer operation time was found for laparoscopic than for open surgery (median 285 versus 158 minutes, p

  6. Trend towards reverse leach process

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    The South African gold mining industry is making notable strides in improving recovery methods for both gold and uranium with significant additions to profits because of higher efficiencies and reductions in costs in the recovery processes. The most notable step on the gold side recently is the adoption of the reverse leach process at Buffelsfontein and Western Deep Levels. This process was pioneered at Hartebeesfontein as far back as 1975 and when introduced there resulted in a two and a half per cent improvement in recovery efficiencies. The essence of reverse leaching under which the uranium is recovered before the gold is the fact that the gold partly coated with iron oxide or locked in uranite, is exposed to be recovered later by cyanidation

  7. A Generalized Reverse Jacket Transform

    OpenAIRE

    Lee, Moon Ho; Rajan, Sundar B; Park, JY

    2001-01-01

    Generalization of the well-known Walsh-Hadamard transform (WHT), namely center-weighted Hadamard transform (CWHT) and complex reverse-jacket transform (CRJT) have been proposed and their fast implementation and simple index generation algorithms have recently been reported. These transforms are of size 2(r) x 2(r) for integral values or r, and defined in terms of binary radix representation of integers. In this paper, using appropriate mixed-radix representation of integers, we present a gene...

  8. Interval orders and reverse mathematics

    OpenAIRE

    Marcone, Alberto

    2006-01-01

    We study the reverse mathematics of interval orders. We establish the logical strength of the implications between various definitions of the notion of interval order. We also consider the strength of different versions of the characterization theorem for interval orders: a partial order is an interval order if and only if it does not contain $2 \\oplus 2$. We also study proper interval orders and their characterization theorem: a partial order is a proper interval order if and only if it cont...

  9. Theory of field reversed configurations

    International Nuclear Information System (INIS)

    Steinhauer, L.C.

    1990-01-01

    This final report surveys the results of work conducted on the theory of field reversed configurations. This project has spanned ten years, beginning in early 1980. During this period, Spectra Technology was one of the leading contributors to the advances in understanding FRC. The report is organized into technical topic areas, FRC formation, equilibrium, stability, and transport. Included as an appendix are papers published in archival journals that were generated in the course of this report. 33 refs

  10. Malware analysis and reverse engineering

    OpenAIRE

    Šváb, Martin

    2014-01-01

    Focus of this thesis is reverse engineering in information technology closely linked with the malware analysis. It explains fundamentals of IA-32 processors architecture and basics of operating system Microsoft Windows. Main part of this thesis is dedicated to the malware analysis, including description of creating a tool for simplification of static part of the analysis. In Conclusion various approaches to the malware analysis, which were described in previous part of the thesis, are practic...

  11. Risperidone-induced reversible neutropenia.

    Science.gov (United States)

    Kattalai Kailasam, Vasanth; Chima, Victoria; Nnamdi, Uchechukwu; Sharma, Kavita; Shah, Kairav

    2017-01-01

    This case report presents a 44-year-old man with a history of schizophrenia who developed neutropenia on risperidone therapy. The patient's laboratory reports showed a gradual decline of leukocytes and neutrophils after resolution and rechallenging. This was reversed with the discontinuation of risperidone and by switching to olanzapine. In this case report, we also discuss the updated evidence base for management of risperidone-induced neutropenia.

  12. Reverse ventilation--perfusion mismatch

    Energy Technology Data Exchange (ETDEWEB)

    Palmaz, J.C.; Barnett, C.A.; Reich, S.B.; Krumpe, P.E.; Farrer, P.A.

    1984-01-01

    Patients having lobar airway obstruction or consolidation usually have decreases of both ventilation and perfusion on lung scans. We report three patients in whom hypoxic vasoconstriction was apparently incomplete, resulting in a ''reversed'' ventilation-perfusion mismatch. Perfusion of the hypoxic lobe on the radionuclide scan was associated with metabolic alkalosis, pulmonary venous and pulmonary arterial hypertension in these patients.

  13. CONCEPTUAL ISSUES REGARDING REVERSE LOGISTICS

    Directory of Open Access Journals (Sweden)

    Ioana Olariu

    2013-12-01

    Full Text Available As the power of consumers is growing, the product return for customer service and customer retention has become a common practice in the competitive market, which propels the recent practice of reverse logistics in companies. Many firms attracted by the value available in the flow, have proactively participated in handling returned products at the end of their usefulness or from other parts of the product life cycle. Reverse logistics is the flow and management of products, packaging, components and information from the point of consumption to the point of origin. It is a collection of practices similar to those of supply chain management, but in the opposite direction, from downstream to upstream. It involves activities such as reuse, repair, remanufacture, refurbish, reclaim and recycle. For the conventional forward logistics systems, the flow starts upstream as raw materials, later as manufactured parts and components to be assembled and continues downstream to reach customers as final products to be disposed once they reach their economic or useful lives. In reverse logistics, the disposed products are pushed upstream to be repaired, remanufactured, refurbished, and disassembled into components to be reused or as raw material to be recycled for later use.

  14. Role of {sup 18}F-choline PET/CT in suspicion of relapse following definitive radiotherapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chondrogiannis, Sotirios; Marzola, Maria Cristina; Maffione, Anna Margherita; Rampin, Lucia; Grassetto, Gaia; Rubello, Domenico [Hospital, Department of Nuclear Medicine, PET/CT Centre, Rovigo (Italy); Ferretti, Alice [Hospital, Medical Physics and Biostatistics Unit, Rovigo (Italy); Nanni, Cristina [University Hospital, Department of Nuclear Medicine, PET/CT Centre, Bologna (Italy); Colletti, Patrick M. [University of Southern California, Los Angeles, CA (United States). Dept. of Radiology

    2013-09-15

    The aims of the study were (a) to evaluate the diagnostic role, by means of positive detection rate (PDR), of {sup 18}F-choline (CH) positron emission tomography (PET)/CT in patients with prostate cancer treated with radiotherapy, with curative intent, and suspicion of relapse during follow-up, (b) to correlate the PDR with trigger prostate-specific antigen (PSA), (c) to investigate the possible influence of androgen deprivation therapy (ADT) at the time of scan on PDR and (d) to assess distribution of metastatic spread. {sup 18}F-CH PET/CT exams from 46 consecutive patients (mean age 71.3 years, range 51-84 years) with prostate cancer (mean Gleason score 6.4, range 5-8) previously treated by definitive radiotherapy and with suspicion of relapse with negative or inconclusive conventional imaging were retrospectively evaluated. Of the 46 patients, 12 were treated with brachytherapy and 34 with external beam radiation therapy. Twenty-three patients were under ADT at the time of the examination. Trigger PSA was measured within 1 month before the exam (mean value 6.5 ng/ml, range 1.1-49.4 ng/ml). Patients were subdivided into four groups according to their PSA level: 1.0 < PSA {<=} 2.0 ng/ml (11 patients), 2.0 < PSA {<=} 4.0 ng/ml (16 patients), 4.0 < PSA {<=} 6.0 ng/ml (9 patients) and PSA > 6.0 ng/ml (10 patients). Correlation between ADT and PDR was investigated as well as between PSA and distribution of metastatic spread. The overall PDR of {sup 18}F-CH PET/CT was 80.4 % (37/46 patients), increasing with the increase of trigger PSA. PDR of {sup 18}F-CH PET/CT is not influenced by ADT (p = 0.710) even if PET performed under ADT demonstrated an overall higher PDR (82.6 %). The majority of the patients (59 %, 22/37 patients) showed local relapse only, confined to the prostatic bed; 22 % of the PET/CT-positive patients (8/37 patients) showed distant relapse only (bone localizations in all of them), while the remaining 19 % (7/37 patients) showed both local and distant

  15. 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

  16. Posterior reversible encephalopathy syndrome in the emergency ...

    African Journals Online (AJOL)

    Posterior reversible encephalopathy syndrome in the emergency service. ... The most common etiologies of PRES are hypertension and renal failure, and the most frequent pathophysiology is hyperperfusion. PRES is ... Keywords: Emergency service, hyperperfusion, posterior reversible encephalopathy, vasogenic edema ...

  17. Application of Sawdust modified with m-DMDHEU/Choline chloride for the removal of CrO4 2- and H2AsO4 - in water

    Science.gov (United States)

    Dang, N. T.; Quan, P. T.; Sang, P. H. P.

    2017-06-01

    This article studies the use of acacia auriculiformis wood sawdust modified with 4,5-dihydroxy-1,3-bis (methoxymethyl) imidazolidin-2-one (m-DMDHEU) and choline chloride for separating CrO4 2- and H2AsO4 - ions in water. NaOH 0.2N/ethanol 70° solution was used to remove lignin from the raw material, the material was then immersed in m-DMDHEU/choline chloride aqueous solution for 24 hours, after that the material was activated at 140oC for one hour. The ability to adsorb and exchange ions of the material was examined using solutions containing CrO4 2- and H2AsO4 - ions in different conditions. The results suggested that the ability to separate CrO4 2- and H2AsO4 - ions of the modified material was better than that of anion resin at pH = 7.0; the chromate adsorption capacity was the highest in acidic condition; the presence of arsenate (V) anions had no effect on the ability to remove chromate. Lastly, the modified material was used to treat water samples containing concentrations of arsenic similar to groundwater in several arsenic-contaminated areas of Vietnam.

  18. 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.

  19. A functional language for describing reversible logic

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal

    2012-01-01

    . Reversibility of descriptions is guaranteed with a type system based on linear types. The language is applied to three examples of reversible computations (ALU, linear cosine transformation, and binary adder). The paper also outlines a design flow that ensures garbage- free translation to reversible logic...

  20. Reversal of sterilization by microsurgical technique.

    Science.gov (United States)

    Gaspari, A L; Ortensi, A; Parlangeli, V; Pellizzari, G; Setti, C; Lania, M

    1988-01-01

    Tubal sterilization techniques that spare the fimbriae and cause the least amount of tubal destruction offer the best chance for reversal of sterilization. Patients seeking reversal of sterilization should be carefully selected. Surgical technique and equipment are important factors in reversal procedures; microsurgical techniques are shown to be more effective than macroscopic techniques.

  1. Cleaning Our World through Reverse Graffiti

    Science.gov (United States)

    Randazzo, Gabe; LaJevic, Lisa

    2013-01-01

    Over the last decade artists have begun to experiment with "reverse pollution" techniques, such as reverse graffiti, which focuses on cleaning environmental surfaces. Having recently been introduced to the works of Moose, the artist known for inventing the reverse graffiti technique, the authors decided to design a curriculum to increase…

  2. Remote Whispering Applying Time Reversal

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Brian Eric [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-07-16

    The purpose of this project was to explore the use of time reversal technologies as a means for communication to a targeted individual or location. The idea is to have the privacy of whispering in one’s ear, but to do this remotely from loudspeakers not located near the target. Applications of this work include communicating with hostages and survivors in rescue operations, communicating imaging and operational conditions in deep drilling operations, monitoring storage of spent nuclear fuel in storage casks without wires, or clandestine activities requiring signaling between specific points. This technology provides a solution in any application where wires and radio communications are not possible or not desired. It also may be configured to self calibrate on a regular basis to adjust for changing conditions. These communications allow two people to converse with one another in real time, converse in an inaudible frequency range or medium (i.e. using ultrasonic frequencies and/or sending vibrations through a structure), or send information for a system to interpret (even allowing remote control of a system using sound). The time reversal process allows one to focus energy to a specific location in space and to send a clean transmission of a selected signal only to that location. In order for the time reversal process to work, a calibration signal must be obtained. This signal may be obtained experimentally using an impulsive sound, a known chirp signal, or other known signals. It may also be determined from a numerical model of a known environment in which the focusing is desired or from passive listening over time to ambient noise.

  3. Presbycusis: reversible with anesthesia drugs?

    Science.gov (United States)

    Kocher, Carl A

    2009-02-01

    Age-related hearing impairment, or presbycusis, is a degenerative condition not currently treatable by medication. It is therefore significant that the author, as a patient, experienced a reversal of high-frequency hearing loss during a 2-day period following abdominal surgery with general anesthesia. This report documents the surgery and the subsequent restoration of hearing, which was bilateral and is estimated to have exceeded 50dB at 4kHz. A possible role is noted for anesthetic agents such as lidocaine, propofol, or fentanyl. This experience may hold a clue for research toward the development of medical treatments for presbycusis.

  4. Optimized reversible binary-coded decimal adders

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Glück, Robert

    2008-01-01

    their design. The optimized 1-decimal BCD full-adder, a 13 × 13 reversible logic circuit, is faster, and has lower circuit cost and less garbage bits. It can be used to build a fast reversible m-decimal BCD full-adder that has a delay of only m + 17 low-power reversible CMOS gates. For a 32-decimal (128-bit...... in reversible logic design by drastically reducing the number of garbage bits. Specialized designs benefit from support by reversible logic synthesis. All circuit components required for optimizing the original design could also be synthesized successfully by an implementation of an existing synthesis algorithm...

  5. Exercise prescription to reverse frailty.

    Science.gov (United States)

    Bray, Nick W; Smart, Rowan R; Jakobi, Jennifer M; Jones, Gareth R

    2016-10-01

    Frailty is a clinical geriatric syndrome caused by physiological deficits across multiple systems. These deficits make it challenging to sustain homeostasis required for the demands of everyday life. Exercise is likely the best therapy to reverse frailty status. Literature to date suggests that pre-frail older adults, those with 1-2 deficits on the Cardiovascular Health Study-Frailty Phenotype (CHS-frailty phenotype), should exercise 2-3 times a week, for 45-60 min. Aerobic, resistance, flexibility, and balance training components should be incorporated but resistance and balance activities should be emphasized. On the other hand, frail (CHS-frailty phenotype ≥ 3 physical deficits) older adults should exercise 3 times per week, for 30-45 min for each session with an emphasis on aerobic training. During aerobic, balance, and flexibility training, both frail and pre-frail older adults should work at an intensity equivalent to a rating of perceived exertion of 3-4 ("somewhat hard") on the Borg CR10 scale. Resistance-training intensity should be based on a percentage of 1-repetition estimated maximum (1RM). Program onset should occur at 55% of 1RM (endurance) and progress to higher intensities of 80% of 1RM (strength) to maximize functional gains. Exercise is the medicine to reverse or mitigate frailty, preserve quality of life, and restore independent functioning in older adults at risk of frailty.

  6. Therapeutic effect of cannabidiol on methionine-choline deficient diet-induced nonalcoholic steatohepatitis in rats and its mechanism

    Directory of Open Access Journals (Sweden)

    Rui CHEN

    2017-08-01

    Full Text Available Objective To observe whether treatment with cannabidiol (CBD affect nonalcoholic steatohepatitis (NASH induced by methionine choline-deficient diet (MCD in rats and investigate the underlying molecular mechanism. Methods Sixty-three adult male SD rats were randomly divided in to three groups as follows: Control group (rats fed with normal diet, MCD group (rats fed with MCD and MCD+CBD group [rats fed with MCD and treated with cannabidiol, 2mg/(kg.d, i.p.]. Ten weeks later, steatohepatitis and fibrosis were evaluated by hematoxylin-eosin and Masson staining, respectively. Serum alanine aminotransferase (ALT and aspartate aminotransferase (AST levels were measured by using an automatic biochemical analyzer and hepatic levels of cholesterol and triacylglycerol were determined with kits. Autophagic flux in livers was evaluated by Western blotting. Results Treatment with cannabidiol reduced ratio of liver/body weightratio (4.2%±0.6% versus 3.1%±0.6%, P<0.05, histological scores (4.7±1.1 versus 2.2±0.5, P<0.05 and fibrosis (1.4%±0.4% versus 0.8%±0.3%, P<0.05 in rat livers, lowered levels of ALT (214.5±54.1U/L versus 92.1±36.0U/L, P<0.05 and AST (175.9±55.2U/L versus 70.8±24.9U/L, P<0.05 in serum, attenuated hepatic fat accumulation (cholesterol, 182.4±42.7mmol/mg protein versus 101.0±33.8mmol/mg protein, P<0.05; triglyceride, 71.4±12.5mmol/mg protein versus 38.7±11.1mmol/mg protein, P<0.05, and down-regulated mRNA expression of Col1A1 (2.9±0.4 versus 1.6±0.3, P<0.05 in livers of rats fed with MCD. Furthermore, cannabidiol led to the LC3 turnover (LC3-II/LC3-I, 37.1±10.8 versus 71.2±17.1, P<0.05 and p62 decrease (202.4±40.9 versus 125.8±32.7, P<0.05 in the livers of MCD-fed rats. Conclusion Treatment with cannabidiol could relieve MCD-induced NASH in rats, at least in part, by autophagic flux promotion. DOI: 10.11855/j.issn.0577-7402.2017.06.07

  7. 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

  8. 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

  9. Reversal of diaschisis by zolpidem

    International Nuclear Information System (INIS)

    Claus, R.P.; Nel, H.W.; Sathekge, M.

    2004-01-01

    Full text: Introduction: Recent literature has reported on clinical improvement after zolpidem, a GABAergic anti insomnia drug, in brain injury and stroke patients. In this study, the effect of zolpidem on crossed cerebellar diaschisis was investigated in such patients. Method: Four patients with crossed cerebellar diaschisis after brain injury or stroke were investigated before and after application of 10 mg zolpidem by 99mTc HMPAO brain SPECT. Result: Apart from clinical improvements, 99mTc HMPAO brain SPECT studies showed reversal of the crossed cerebellar diaschisis and improvement of perfusion defects after zolpidem. Conclusion: 99mTc HMPAO brain SPECT may have a role to pre-select brain injury and stroke patients who will benefit clinically from zolpidem therapy. (author)

  10. How to play Reverse Hex

    DEFF Research Database (Denmark)

    Toft, Bjarne; Hayward, Ryan B.; Henderson, Philip

    2012-01-01

    We present new results on how to play Reverse Hex, also known as Rex, or Misère Hex, on n × n boards. We give new proofs – and strengthened versions – of Lagarias and Sleator’s theorem (for n × n boards, each player can prolong the game until the board is full, so the first/second player can always...... win if n is even/odd) and Evans’s theorem (for even n, the acute corner is a winning opening move for the first player). Also, for even n ≥ 4, we find another first-player winning opening (adjacent to the acute corner, on the first player’s side), and for odd n ≥ 3, and for each first-player opening......, we find second-player winning replies. Finally, in response to comments by Martin Gardner, for each n ≤ 5, we give a simple winning strategy for the n × n board....

  11. Model of reverse steam generator

    International Nuclear Information System (INIS)

    Malasek, V.; Manek, O.; Masek, V.; Riman, J.

    1987-01-01

    The claim of Czechoslovak discovery no. 239272 is a model designed for the verification of the properties of a reverse steam generator during the penetration of water, steam-water mixture or steam into liquid metal flowing inside the heat exchange tubes. The design may primarily be used for steam generators with a built-in inter-tube structure. The model is provided with several injection devices configured in different heat exchange tubes, spaced at different distances along the model axis. The design consists in that between the pressure and the circumferential casings there are transverse partitions and that in one chamber consisting of the circumferential casings, pressure casing and two adjoining partitions there is only one passage of the injection device through the inter-tube space. (Z.M.). 1 fig

  12. Regulation of Nutritional Metabolism in Transition Dairy Cows: Energy Homeostasis and Health in Response to Post-Ruminal Choline and Methionine.

    Science.gov (United States)

    Sun, Feifei; Cao, Yangchun; Cai, Chuanjiang; Li, Shengxiang; Yu, Chao; Yao, Junhu

    2016-01-01

    This study investigated the effects of rumen-protected methionine (RPM) and rumen-protected choline (RPC) on energy balance, postpartum lactation performance, antioxidant capacity and immune response in transition dairy cows. Forty-eight multiparous transition cows were matched and divided into four groups: control, 15 g/d RPC, 15 g/d RPM or 15 g/d RPC + 15 g/d RPM. Diet samples were collected daily before feeding, and blood samples were collected weekly from the jugular vein before morning feeding from 21 days prepartum to 21 days postpartum. Postpartum dry matter intake (DMI) was increased by both additives (P cows were improved after parturition (P cows. The results demonstrated that dietary supplementation with RPC and RPM promoted energy balance by increasing postpartal DMI and regulating hepatic lipid metabolism, improved postpartum lactation performance and enhanced antioxidant capacity and immune function of transition dairy cows.

  13. Evaluation of rumen-protected choline additive to diet on productive performance of male Zaraibi growing goats during hot summer season in Egypt.

    Science.gov (United States)

    Habeeb, A A M; Gad, A E; Atta, M A A; Abdel-Hafez, M A M

    2017-08-01

    Twenty Zaraibi goat bucks were used in this experiment which lasted 3 months during summer season of Egypt. The animals were divided randomly into two equal groups. The first group was kept without treatment as control while in the second group, rumen-protected choline (RPC) at the level of 20 g/buck/day was added to the concentrate feed mixture at the morning feeding. RPC additives to diet of Zaraibi goat bucks during the period of hot summer season increased (P conversion while water intake was not affected by RPC additives. RPC increased (P goats, especially, under heat stress conditions of summer season in Egypt and showed the best results concerning the growth, feed conversion, blood metabolites, and economic efficiency.

  14. Choline chloride (ChCl) and monosodium glutamate (MSG)-based green solvents from optimized cactus malic acid for biomass delignification.

    Science.gov (United States)

    Yiin, Chung Loong; Quitain, Armando T; Yusup, Suzana; Uemura, Yoshimitsu; Sasaki, Mitsuru; Kida, Tetsuya

    2017-11-01

    This work aimed to develop an efficient microwave-hydrothermal (MH) extraction of malic acid from abundant natural cactus as hydrogen bond donor (HBD) whereby the concentration was optimized using response surface methodology. The ideal process conditions were found to be at a solvent-to-feed ratio of 0.008, 120°C and 20min with 1.0g of oxidant, H 2 O 2 . Next generation environment-friendly solvents, low transition temperature mixtures (LTTMs) were synthesized from cactus malic acid with choline chloride (ChCl) and monosodium glutamate (MSG) as hydrogen bond acceptors (HBAs). The hydrogen-bonding interactions between the starting materials were determined. The efficiency of the LTTMs in removing lignin from oil palm biomass residues, empty fruit bunch (EFB) was also evaluated. The removal of amorphous hemicellulose and lignin after the pretreatment process resulted in an enhanced digestibility and thermal degradability of biomass. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Principles of a reversible programming language

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2008-01-01

    The principles of reversible programming languages are explicated and illustrated with reference to the design of a high-level imperative language, Janus. The fundamental properties for such languages include backward as well as forward determinism and reversible updates of data. The unique design...... features of the language include explicit post-condition assertions, direct access to an inverse semantics and the possibility of clean (i.e., garbage-free) computation of injective functions. We suggest the clean simulation of reversible Turing machines as a criterion for computing strength of reversible...... languages, and demonstrate this for Janus. We show the practicality of the language by implementation of a reversible fast Fourier transform. Our results indicate that the reversible programming paradigm has fundamental properties that are relevant to many different areas of computer science....

  16. 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.

  17. The effect of choline-stabilized orthosilicic acid on microelements and silicon concentration, photosynthesis activity and yield of tomato grown under Mn stress.

    Science.gov (United States)

    Kleiber, Tomasz; Calomme, Mario; Borowiak, Klaudia

    2015-11-01

    The aim of experiments was to assess the efficiency of choline-stabilized orthosilicic acid (ch-OSA; complex of orthosilicic acid with choline and a bioavailable source of silicon) application under increasing manganese (Mn) stress on the micronutritional composition and yielding of tomato (Solanum lycopersicum L. cvs. 'Alboney F1' and 'Emotion F1'). Plants were grown in rockwool with the application of a nutrient solution varied the Mn concentrations (in mg dm(-3)): 9.6 and 19.2 which cause strong oxidative stress of plants comparing with optimal concentration of that microelement in nutrient solution. The effect of ch-OSA application (at Si concentration of 0.3 mg dm(-3) nutrient solution) was investigated at both Mn-levels. Increasing Mn stress modified the concentration of microelements and silicon (Si) in tomato leaves. Application of ch-OSA also influenced the concentration of nutrients, but the determined changes were generally multidirectional and varied depending on Mn-level and cultivar. Under the increasing Mn stress a significant downward trend was observed for the mean concentration of Fe (in both cultivars) in fruits--but changes of Mn, Zn and Cu were varied depend on cultivar. In the case of cv. 'Alboney F1' ch-OSA application caused an increase the mean concentrations of Fe, Zn and Cu, while in the case of cv. 'Emotion F1' the reduction of mean concentrations of Zn and Cu was recorded. Ch-OSA treatment did not influence on the Mn concentrations in fruits. A beneficial role of ch-OSA was also found in photosynthesis activity. This was especially valid for lower levels of Mn. Application of ch-OSA improved significantly the marketable yield of tomato under stress by a low Mn level. Copyright © 2015 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  18. 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.

  19. 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.

  20. 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

  1. Mitochondrially-targeted bacterial phosphatidylethanolamine methyltransferase sustained phosphatidylcholine synthesis of a Saccharomyces cerevisiae Δpem1 Δpem2 double mutant without exogenous choline supply.

    Science.gov (United States)

    Kobayashi, Shingo; Mizuike, Aya; Horiuchi, Hiroyuki; Fukuda, Ryouichi; Ohta, Akinori

    2014-09-01

    In eukaryotic cells, phospholipids are synthesized exclusively in the defined organelles specific for each phospholipid species. To explain the reason for this compartmental specificity in the case of phosphatidylcholine (PC) synthesis, we constructed and characterized a Saccharomyces cerevisiae strain that lacked endogenous phosphatidylethanolamine (PE) methyltransferases but had a recombinant PE methyltransferase from Acetobacter aceti, which was fused with a mitochondrial targeting signal from yeast Pet100p and a 3×HA epitope tag. This fusion protein, which we named as mitopmt, was determined to be localized to the mitochondria by fluorescence microscopy and subcellular fractionation. The expression of mitopmt suppressed the choline auxotrophy of a double deletion mutant of PEM1 and PEM2 (pem1Δpem2Δ) and enabled it to synthesize PC in the absence of choline. This growth suppression was observed even if the Kennedy pathway was inactivated by the repression of PCT1 encoding CTP:phosphocholine cytidylyltransferase, suggesting that PC synthesized in the mitochondria is distributed to other organelles without going through the salvage pathway. The pem1Δpem2Δ strain deleted for PSD1 encoding the mitochondrial phosphatidylserine decarboxylase was able to grow because of the expression of mitopmt in the presence of ethanolamine, implying that PE from other organelles, probably from the ER, was converted to PC by mitopmt. These results suggest that PC could move out of the mitochondria, and raise the possibility that its movement is not under strict directional limitations. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Evaluation of Methionine Content in a High-Fat and Choline-Deficient Diet on Body Weight Gain and the Development of Non-Alcoholic Steatohepatitis in Mice.

    Science.gov (United States)

    Chiba, Tsuyoshi; Suzuki, Sachina; Sato, Yoko; Itoh, Tatsuki; Umegaki, Keizo

    2016-01-01

    Non-alcoholic steatohepatitis (NASH) is a globally recognized liver disease. A methionine- and choline-deficient diet is used to induce NASH in mice; however, this diet also causes severe body weight loss. To resolve this issue, we examined the effects of methionine content in a high-fat and choline-deficient (HFCD) diet on body weight and the development of NASH in mice. C57BL/6J mice (male, 10 weeks of age) were fed an L-amino acid rodent (control) diet, high-fat (HF) diet, or HFCD diet containing various amounts of methionine (0.1-0.6% (w/w)) for 12 weeks. Plasma lipid levels, hepatic lipid content and inflammatory marker gene expression were measured, and a pathological analysis was conducted to evaluate NASH. The 0.1% methionine in HFCD diet suppressed body weight gain, which was lower than that with control diet. On the other hand, the 0.2% methionine in HFCD diet yielded similar body weight gains as the control diet, while more than 0.4% methionine showed the same body weight gains as the HF diet. Liver weights and hepatic lipid contents were the greatest with 0.1% methionine and decreased in a methionine dose-dependent manner. Pathological analysis, NAFLD activity scores and gene expression levels in the liver revealed that 0.1% and 0.2% methionine for 12 weeks induced NASH, whereas 0.4% and 0.6% methionine attenuated the induction of NASH by HFCD diet. However, the 0.2% methionine in HFCD diet did not induce insulin resistance, despite the body weight gain. The 0.2% methionine in HFCD diet for 12 weeks was able to induce NASH without weight loss.

  3. Integrated Pumped Hydro Reverse Osmosis systems

    OpenAIRE

    Trimble, A Zachary; Ferrara, Marco; Slocum, Alexander H; Haji, Maha Niametullah; Ghaemsaidi, Sasan John

    2016-01-01

    Ideal head height for pumped hydro energy storage/generation systems and reverse osmosis desalination plants coincide (500–700 m). Many drought stricken coastal regions have nearby mountains of sufficient elevation to support upper reservoirs at this ideal head height. A good symbiotic match might thus be realized by co-locating a pumped hydro plant with a reverse osmosis desalination plant, which we call an Integrated Pumped Hydro Reverse Osmosis (IPHRO) system. Combining systems reduces cap...

  4. Gravity controlled anti-reverse rotation device

    Science.gov (United States)

    Dickinson, Robert J.; Wetherill, Todd M.

    1983-01-01

    A gravity assisted anti-reverse rotation device for preventing reverse rotation of pumps and the like. A horizontally mounted pawl is disposed to mesh with a fixed ratchet preventing reverse rotation when the pawl is advanced into intercourse with the ratchet by a vertically mounted lever having a lumped mass. Gravitation action on the lumped mass urges the pawl into mesh with the ratchet, while centrifugal force on the lumped mass during forward, allowed rotation retracts the pawl away from the ratchet.

  5. Is there a role for {sup 11}C-choline PET/CT in the early detection of metastatic disease in surgically treated prostate cancer patients with a mild PSA increase <1.5 ng/ml?

    Energy Technology Data Exchange (ETDEWEB)

    Castellucci, Paolo [University of Bologna, Service of Nuclear Medicine, Department of Haematology-Oncology and Laboratory Medicine, Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant' Orsola-Malpighi, Bologna (Italy); Azienda Ospedaliero-Unversitaria di Bologna Policlinico Sant' Orsola-Malpighi, UO di Medicina Nucleare, PAD. 30, Bologna (Italy); Fuccio, Chiara; Santi, Ivan; Nanni, Cristina; Allegri, Vincenzo; Montini, Gian Carlo; Ambrosini, Valentina; Boschi, Stefano; Fanti, Stefano [University of Bologna, Service of Nuclear Medicine, Department of Haematology-Oncology and Laboratory Medicine, Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant' Orsola-Malpighi, Bologna (Italy); Rubello, Domenico; Marzola, Maria Cristina [Sanata Maria della Misericordia Hospital, Department of Nuclear Medicine, Medical Physics, Radiology, Service of Nuclear Medicine, PET/CT Centre, Rovigo (Italy); Schiavina, Riccardo; Martorana, Giuseppe [University of Bologna, Service of Urology, Department of Specialist Surgery and Anaesthesiology, Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant' Orsola-Malpighi, Bologna (Italy)

    2011-01-15

    The aim of this study was to evaluate the potential usefulness of whole-body {sup 11}C-choline PET/CT in the re-staging of prostate cancer (PC) patients previously treated with radical prostatectomy (RP), who presented a mild increase of prostate-specific antigen (PSA) <1.5 ng/ml (early biochemical relapse) during follow-up (FU). We evaluated 102 consecutive patients (mean age = 68 years, range = 54-82 years) previously treated with RP and who presented during FU a mild increase of trigger PSA serum levels <1.5 ng/ml: mean 0.86 {+-} 0.40 ng/ml (range 0.2-1.5) and median 0.93 ng/ml (range 0.67-1.10). In this patient series {sup 11}C-choline PET/CT was used as the first imaging examination at the time of the detection of a mild serum PSA increase <1.5 ng/ml. {sup 11}C-Choline PET/CT was performed following standard procedures in our centre. At the time of PET/CT, 86 patients were not receiving any pharmacologic treatment, while 16 were under anti-androgenic therapy. Positive PET findings were validated by: (a) transrectal ultrasound (TRUS)-guided biopsy in cases of local recurrence, (b) surgical lymphadenectomy, (c) other imaging procedures or (d) FU lasting for at least 12 months. Univariate and multivariate analyses were used to evaluate the following variables: age, TNM staging, Gleason score, time from RP to the biochemical relapse, anti-androgen therapy at the time of {sup 11}C-choline PET/CT scan, trigger PSA value and PSA kinetics, i.e. PSA doubling time (PSAdt) and PSA velocity (PSAvel), in order to assess the significant predictive factors related to the findings of a positive {sup 11}C-choline PET/CT scan. Overall, {sup 11}C-choline PET/CT showed positive findings in 29 of 102 patients (28% of cases). In detail, {sup 11}C-choline PET/CT detected: local relapse in 7 patients, bone metastases in 13 patients (4 single and 9 multiple) and lymph node metastases in 9 patients (6 single and 3 multiple). Positive PET findings were validated by: (a) TRUS

  6. Reverse Engineering Adverse Outcome Pathways

    Energy Technology Data Exchange (ETDEWEB)

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  7. Reverse genetics in ecological research.

    Directory of Open Access Journals (Sweden)

    Jens Schwachtje

    2008-02-01

    Full Text Available By precisely manipulating the expression of individual genetic elements thought to be important for ecological performance, reverse genetics has the potential to revolutionize plant ecology. However, untested concerns about possible side-effects of the transformation technique, caused by Agrobacterium infection and tissue culture, on plant performance have stymied research by requiring onerous sample sizes. We compare 5 independently transformed Nicotiana attenuata lines harboring empty vector control (EVC T-DNA lacking silencing information with isogenic wild types (WT, and measured a battery of ecologically relevant traits, known to be important in plant-herbivore interactions: phytohormones, secondary metabolites, growth and fitness parameters under stringent competitive conditions, and transcriptional regulation with microarrays. As a positive control, we included a line silenced in trypsin proteinase inhibitor gene (TPI expression, a potent anti-herbivore defense known to exact fitness costs in its expression, in the analysis. The experiment was conducted twice, with 10 and 20 biological replicates per genotype. For all parameters, we detected no difference between any EVC and WT lines, but could readily detect a fitness benefit of silencing TPI production. A statistical power analyses revealed that the minimum sample sizes required for detecting significant fitness differences between EVC and WT was 2-3 orders of magnitude larger than the 10 replicates required to detect a fitness effect of TPI silencing. We conclude that possible side-effects of transformation are far too low to obfuscate the study of ecologically relevant phenotypes.

  8. Reversible hypothyroidism and Whipple's disease

    Directory of Open Access Journals (Sweden)

    Tran Huy A

    2006-05-01

    Full Text Available Abstract Background The major cause of primary hypothyroidism is autoimmune mediated with progressive and permanent destruction of the thyroid gland resulting in life-long replacement therapy. Treatable and reversible hypothyroidism is unusual and here forth is such a case due to infection of the thyroid gland with Tropheryma whippleii, Whipple disease. Case presentation A 45 year-old female presented with symptoms and signs consistent with primary hypothyroidism, which was also confirmed biochemically. Her response to thyroxine replacement therapy was poor however, requiring a significantly elevated amount. Further investigation revealed the presence of Whipple's disease involving the gastrointestinal trace and possibly the thyroid gland. Her thyroxine requirement decreased drastically following appropriate antimicrobial therapy for Whipple's disease to the extent that it was ceased. Thyrotropin releasing hormone testing in the steady state suggested there was diminished thyroid reserve due to Whipple's disease. Conclusion This is the first ante-mortem case report studying the possible involvement of the thyroid gland by Whipple's disease. Despite the normalization of her thyroid function test biochemically after antibiotic therapy, there is diminished thyroid reserve thus requiring close and regular monitoring.

  9. Reverse Transcriptase and Cellular Factors: Regulators of HIV-1 Reverse Transcription

    OpenAIRE

    Warren, Kylie; Warrilow, David; Meredith, Luke; Harrich, David

    2009-01-01

    There is ample evidence that synthesis of HIV-1 proviral DNA from the viral RNA genome during reverse transcription requires host factors. However, only a few cellular proteins have been described in detail that affect reverse transcription and interact with reverse transcriptase (RT). HIV-1 integrase is an RT binding protein and a number of IN-binding proteins including INI1, components of the Sin3a complex, and Gemin2 affect reverse transcription. In addition, recent studies implicate the c...

  10. 14 CFR 25.507 - Reversed braking.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Reversed braking. 25.507 Section 25.507 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Structure Ground Loads § 25.507 Reversed braking. (a) The airplane...

  11. Evaluation of reversible contraceptive activities of Annona ...

    African Journals Online (AJOL)

    Evaluation of reversible contraceptive activities of Annona squamosa (Linn.) ... Plant Products Research Journal ... Therefore the present study was undertaken to evaluate the contraceptive activities of methanol extract of the stem bark of Annoa squamosa L. (Annonaceae) with their respective reversibility in male rats.

  12. Kronisk ileus efter iatrogen reversering af tyndtarmen

    DEFF Research Database (Denmark)

    Pedersen, Mark Ellebaek; Rahr, Hans B; Mahdi, Bassam

    2010-01-01

    We report a case of inadvertent reversal of the entire small intestine leading to severe complications and long-standing ileus. The clinical diagnosis was confirmed by magnetic resonance imaging and laparotomy. The patient was cured by surgical re-reversal of the bowel. Care should be taken to ma...... the bowel ends when multiple simultaneous bowel resections are performed....

  13. Reverse engineering of the robot base platform

    International Nuclear Information System (INIS)

    Anwar A Rahman; Azizul Rahman A Aziz; Mohd Arif Hamzah; Muhd Nor Atan; Fadil Ismail; Rosli Darmawan

    2009-01-01

    The robot base platform used to place the robotic arm version 2 was imported through a local company. The robot base platform is used as a reference for reverse egineering development for a smaller size robot. The paper will discuss the reverse engineering design process and parameters involved in the development of the robot base platform. (Author)

  14. Reversing Africa's Decline. Worldwatch Paper 65.

    Science.gov (United States)

    Brown, Lester R.; Wolf, Edward C.

    This paper highlights some of the themes that any successful strategy to reverse the decline of Africa must embrace. Africa is a continent experiencing a breakdown in the relationship between people and their natural support systems. Famine and the threat of famine are among the manifestations of this breakdown. This decline can be reversed. To do…

  15. Reverse Methanogenesis and Respiration in Methanotrophic Archaea

    NARCIS (Netherlands)

    Timmers, Peer H.A.; Welte, Cornelia U.; Koehorst, Jasper J.; Plugge, Caroline M.; Jetten, Mike S.M.; Stams, Alfons J.M.

    2017-01-01

    Anaerobic oxidation of methane (AOM) is catalyzed by anaerobic methane-oxidizing archaea (ANME) via a reverse and modified methanogenesis pathway. Methanogens can also reverse the methanogenesis pathway to oxidize methane, but only during net methane production (i.e., "trace methane oxidation"). In

  16. Vibrational dynamics of ice in reverse micelles

    NARCIS (Netherlands)

    Dokter, A.M.; Petersen, C.; Woutersen, S.; Bakker, H.J.

    2008-01-01

    he ultrafast vibrational dynamics of HDO:D2O ice at 180 K in anionic reverse micelles is studied by midinfrared femtosecond pump-probe spectroscopy. Solutions containing reverse micelles are cooled to low temperatures by a fast-freezing procedure. The heating dynamics of the micellar solutions is

  17. Online Reverse Auctions for Procurement of Services

    NARCIS (Netherlands)

    U.L. Radkevitch (Uladzimir)

    2008-01-01

    textabstractOnline reverse auctions, in which a buyer seeks to select a supplier and suppliers compete for contracts by bidding online, revolutionized corporate procurement early this century. Shortly after they had been pioneered by General Electric, many companies rushed to adopt reverse auctions

  18. Reversible logic gates on Physarum Polycephalum

    International Nuclear Information System (INIS)

    Schumann, Andrew

    2015-01-01

    In this paper, we consider possibilities how to implement asynchronous sequential logic gates and quantum-style reversible logic gates on Physarum polycephalum motions. We show that in asynchronous sequential logic gates we can erase information because of uncertainty in the direction of plasmodium propagation. Therefore quantum-style reversible logic gates are more preferable for designing logic circuits on Physarum polycephalum

  19. Reverse-symmetry waveguides: Theory and fabrication

    DEFF Research Database (Denmark)

    Horvath, R.; Lindvold, Lars René; Larsen, N.B.

    2002-01-01

    We present an extensive theoretical analysis of reverse-symmetry waveguides with special focus on their potential application as sensor components in aqueous media and demonstrate a novel method for fabrication of such waveguides. The principle of reverse symmetry is based on making the refractive...

  20. Reversal of laryngotracheal separation in paediatric patients.

    LENUS (Irish Health Repository)

    Young, Orla

    2012-02-01

    OBJECTIVE: Laryngotracheal separation (LTS) is an effective and reliable definitive treatment for intractable aspiration. A major advantage of this treatment for intractable aspiration is its\\' potential reversibility. Should the underlying disorder improve, a reversal of the procedure may be attempted. This has been successfully achieved in the adult population. To our knowledge, no previous cases have been reported of successful reversal of LTS in children. METHODS: A retrospective review from 2003 to 2010 identified four cases of intractable aspiration treated with LTS in our department. Two of these patients displayed objective evidence of sufficient recovery of their underlying aspiration to consider reversal. Patient selection for reversal was dependent upon successful oral intake for 9 months along with videofluoroscopic evidence of normal or minimally impaired swallow. RESULTS: Two children who were successfully treated for intractable aspiration with LTS demonstrated objective evidence of recovery sufficient to attempt reversal. Both children underwent successful surgical reversal of LTS using a cricotracheal resection with end-to-end anastamosis, similar to that used in treatment of subglottic stenosis. Both children can now tolerate oral diet and their speech and language development is in line with their overall developmental level. CONCLUSIONS: Laryngotracheal separation is an effective and reliable definitive treatment for intractable aspiration facilitating protection of the airway and allowing safe swallowing with unimpeded respiration, but with the major drawback of loss of phonation. To our knowledge, we document the first two cases of successful LTS reversal in children.

  1. Reverse engineering a visual age application

    NARCIS (Netherlands)

    Sneed, Harry M.; Verhoef, Chris

    2015-01-01

    This paper is an industrial case study of how a VisualAge application system on an IBM mainframe was reverse engineered into a system reference repository. The starting point was the code fragments generated by the VisualAge interactive development tool. The results of the reverse engineering

  2. Multiple reversal olfactory learning in honeybees

    Directory of Open Access Journals (Sweden)

    Theo Mota

    2010-07-01

    Full Text Available In multiple reversal learning, animals trained to discriminate a reinforced from a non-reinforced stimulus are subjected to various, successive reversals of stimulus contingencies (e.g. A+ vs. B-, A- vs. B+, A+ vs. B-. This protocol is useful to determine whether or not animals learn to learn and solve successive discriminations faster (or with fewer errors with increasing reversal experience. Here we used the olfactory conditioning of proboscis extension reflex to study how honeybees Apis mellifera perform in a multiple reversal task. Our experiment contemplated four consecutive differential conditioning phases involving the same odors (A+ vs. B- to A- vs. B+ to A+ vs. B- to A- vs. B+. We show that bees in which the weight of reinforced or non-reinforced stimuli was similar mastered the multiple olfactory reversals. Bees which failed the task exhibited asymmetric responses to reinforced and non-reinforced stimuli, thus being unable to rapidly reverse stimulus contingencies. Efficient reversers did not improve their successive discriminations but rather tended to generalize their choice to both odors at the end of conditioning. As a consequence, both discrimination and reversal efficiency decreasedalong experimental phases. This result invalidates a learning-to-learn effect and indicates that bees do not only respond to the actual stimulus contingencies but rather combine these with an average of past experiences with the same stimuli.  

  3. The Rate Laws for Reversible Reactions.

    Science.gov (United States)

    King, Edward L.

    1986-01-01

    Provides background information for teachers on the rate laws for reversible reactions. Indicates that although prediction of the form of the rate law for a reverse reaction given the rate law for the forward reaction is not certain, the number of possibilities is limited because of relationships described. (JN)

  4. Estimation and uncertainty of reversible Markov models.

    Science.gov (United States)

    Trendelkamp-Schroer, Benjamin; Wu, Hao; Paul, Fabian; Noé, Frank

    2015-11-07

    Reversibility is a key concept in Markov models and master-equation models of molecular kinetics. The analysis and interpretation of the transition matrix encoding the kinetic properties of the model rely heavily on the reversibility property. The estimation of a reversible transition matrix from simulation data is, therefore, crucial to the successful application of the previously developed theory. In this work, we discuss methods for the maximum likelihood estimation of transition matrices from finite simulation data and present a new algorithm for the estimation if reversibility with respect to a given stationary vector is desired. We also develop new methods for the Bayesian posterior inference of reversible transition matrices with and without given stationary vector taking into account the need for a suitable prior distribution preserving the meta-stable features of the observed process during posterior inference. All algorithms here are implemented in the PyEMMA software--http://pyemma.org--as of version 2.0.

  5. Magnetic reversals from planetary dynamo waves

    DEFF Research Database (Denmark)

    Sheyko, Andrey; Finlay, Chris; Jackson, Andrew

    2016-01-01

    A striking feature of many natural dynamos is their ability to undergo polarity reversals. The best documented example is Earth's magnetic field, which has reversed hundreds of times during its history. The origin of geomagnetic polarity reversals lies in a magnetohydrodynamic process that takes...... place in Earth's core, but the precise mechanism is debated. The majority of numerical geodynamo simulations that exhibit reversals operate in a regime in which the viscosity of the fluid remains important, and in which the dynamo mechanism primarily involves stretching and twisting of field lines...... (the ratio of advection to Coriolis force). Instead, stretching of the magnetic field by a strong shear in the east-west flow near the imaginary cylinder just touching the inner core and parallel to the axis of rotation is crucial to the reversal mechanism in our models, which involves a process akin...

  6. Designing Novel Quaternary Quantum Reversible Subtractor Circuits

    Science.gov (United States)

    Haghparast, Majid; Monfared, Asma Taheri

    2018-01-01

    Reversible logic synthesis is an important area of current research because of its ability to reduce energy dissipation. In recent years, multiple valued logic has received great attention due to its ability to reduce the width of the reversible circuit which is a main requirement in quantum technology. Subtractor circuits are between major components used in quantum computers. In this paper, we will discuss the design of a quaternary quantum reversible half subtractor circuit using quaternary 1-qudit, 2-qudit Muthukrishnan-Stroud and 3-qudit controlled gates and a 2-qudit Generalized quaternary gate. Then a design of a quaternary quantum reversible full subtractor circuit based on the quaternary half subtractor will be presenting. The designs shall then be evaluated in terms of quantum cost, constant input, garbage output, and hardware complexity. The proposed quaternary quantum reversible circuits are the first attempt in the designing of the aforementioned subtractor.

  7. Structure and reactivity in reverse micelles

    International Nuclear Information System (INIS)

    Pileni, M.P.

    1989-01-01

    This book gives an up-to-date, comprehensive assessment of current knowledge in the very fast-moving field of reverse micelles, ranging from physical studies to biotechnological applications. Starting with physical and spectroscopic studies of reverse micelle structure at the macro- and microstructural levels, topics dealt with in detail are the NMR spectroscopy of reverse micells, fluorescence quenching kinetics, photochemical behaviour, role and behaviour of hydrated electrons in reverse micelles, including femtosecond phenomena, reactivity-dependent applications such as microlatex formation, protein partitioning, extraction, and purification. The microreactor characteristics of reverse micelles are shown to allow formation of semiconductor clusters, peptide synthesis through enzyme-catalyzed reactions, reaction product extraction, and enhanced-reactivity phenomena. The reactivity effects and their consequences are particularly highlighted throughout the book

  8. Reversed field pinch ignition requirements

    International Nuclear Information System (INIS)

    Werley, K.A.

    1991-01-01

    Plasma models are described and used to calculated numerically the transport confinement (nτ E ) requirements and steady state operation points for both the reversed field pinch (RFP) and the tokamak. The models are used to examine the CIT tokamak ignition conditions and the RFP experimental and ignition conditions. Physics differences between RFPs and tokamaks and their consequences for a D-T ignition machine are discussed. Compared with a tokamak, the ignition RFP has many physics advantages, including Ohmic heating to ignition (no need for auxiliary heating systems), higher beta, lower ignition current, less sensitivity of ignition requirements to impurity effects, no hard disruptions (associated with beta or density limits) and successful operation with high radiation fractions (f RAD ∼ 0.95). These physics advantages, coupled with important engineering advantages associated with lower external magnetic field, larger aspect ratios and smaller plasma cross-sections, translate to significant cost reductions for both ignition and reactor applications. The primary drawback of the RFP is the uncertainty that the present scaling will extrapolate to reactor regimes. Devices that are under construction should go a long way toward resolving this scaling uncertainty. The 4 MA ZTH is expected to extend the nτ E transport scaling data by three orders of magnitude above the results of ZT-40M, and, if the present scaling holds, ZTH is expected to achieve a D-T equivalent scientific energy breakeven, Q = 1. A base case RFP ignition point is identified with a plasma current of 8.1 MA and no auxiliary heating. (author). 19 refs, 11 figs, 3 tabs

  9. Reversible machine code and its abstract processor architecture

    DEFF Research Database (Denmark)

    Axelsen, Holger Bock; Glück, Robert; Yokoyama, Tetsuo

    2007-01-01

    A reversible abstract machine architecture and its reversible machine code are presented and formalized. For machine code to be reversible, both the underlying control logic and each instruction must be reversible. A general class of machine instruction sets was proven to be reversible, building ...... on our concept of reversible updates. The presentation is abstract and can serve as a guideline for a family of reversible processor designs. By example, we illustrate programming principles for the abstract machine architecture formalized in this paper....

  10. Chemical reactions in reverse micelle systems

    Science.gov (United States)

    Matson, Dean W.; Fulton, John L.; Smith, Richard D.; Consani, Keith A.

    1993-08-24

    This invention is directed to conducting chemical reactions in reverse micelle or microemulsion systems comprising a substantially discontinuous phase including a polar fluid, typically an aqueous fluid, and a microemulsion promoter, typically a surfactant, for facilitating the formation of reverse micelles in the system. The system further includes a substantially continuous phase including a non-polar or low-polarity fluid material which is a gas under standard temperature and pressure and has a critical density, and which is generally a water-insoluble fluid in a near critical or supercritical state. Thus, the microemulsion system is maintained at a pressure and temperature such that the density of the non-polar or low-polarity fluid exceeds the critical density thereof. The method of carrying out chemical reactions generally comprises forming a first reverse micelle system including an aqueous fluid including reverse micelles in a water-insoluble fluid in the supercritical state. Then, a first reactant is introduced into the first reverse micelle system, and a chemical reaction is carried out with the first reactant to form a reaction product. In general, the first reactant can be incorporated into, and the product formed in, the reverse micelles. A second reactant can also be incorporated in the first reverse micelle system which is capable of reacting with the first reactant to form a product.

  11. Reversible Lithium Neurotoxicity: Review of the Literature

    Science.gov (United States)

    Netto, Ivan

    2012-01-01

    Objective: Lithium neurotoxicity may be reversible or irreversible. Reversible lithium neurotoxicity has been defined as cases of lithium neurotoxicity in which patients recovered without any permanent neurologic sequelae, even after 2 months of an episode of lithium toxicity. Cases of reversible lithium neurotoxicity differ in clinical presentation from those of irreversible lithium neurotoxicity and have important implications in clinical practice. This review aims to study the clinical presentation of cases of reversible lithium neurotoxicity. Data Sources: A comprehensive electronic search was conducted in the following databases: MEDLINE (PubMed), 1950 to November 2010; PsycINFO, 1967 to November 2010; and SCOPUS (EMBASE), 1950 to November 2010. MEDLINE and PsycINFO were searched by using the OvidSP interface. Study Selection: A combination of the following search terms was used: lithium AND adverse effects AND central nervous system OR neurologic manifestation. Publications cited include articles concerned with reversible lithium neurotoxicity. Data Extraction: The age, sex, clinical features, diagnostic categories, lithium doses, serum lithium levels, precipitating factors, and preventive measures of 52 cases of reversible lithium neurotoxicity were extracted. Data Synthesis: Among the 52 cases of reversible lithium neurotoxicity, patients ranged in age from 10 to 80 years and a greater number were female (P = .008). Most patients had affective disorders, schizoaffective disorders, and/or depression (P lithium levels were less than or equal to 1.5 mEq/L (P lithium, underlying brain pathology, abnormal tissue levels, specific diagnostic categories, and elderly populations were some of the precipitating factors reported for reversible lithium neurotoxicity. The preventive measures were also described. Conclusions: Reversible lithium neurotoxicity presents with a certain clinical profile and precipitating factors for which there are appropriate

  12. Reversible lithium neurotoxicity: review of the literatur.

    Science.gov (United States)

    Netto, Ivan; Phutane, Vivek H

    2012-01-01

    Lithium neurotoxicity may be reversible or irreversible. Reversible lithium neurotoxicity has been defined as cases of lithium neurotoxicity in which patients recovered without any permanent neurologic sequelae, even after 2 months of an episode of lithium toxicity. Cases of reversible lithium neurotoxicity differ in clinical presentation from those of irreversible lithium neurotoxicity and have important implications in clinical practice. This review aims to study the clinical presentation of cases of reversible lithium neurotoxicity. A comprehensive electronic search was conducted in the following databases: MEDLINE (PubMed), 1950 to November 2010; PsycINFO, 1967 to November 2010; and SCOPUS (EMBASE), 1950 to November 2010. MEDLINE and PsycINFO were searched by using the OvidSP interface. A combination of the following search terms was used: lithium AND adverse effects AND central nervous system OR neurologic manifestation. Publications cited include articles concerned with reversible lithium neurotoxicity. The age, sex, clinical features, diagnostic categories, lithium doses, serum lithium levels, precipitating factors, and preventive measures of 52 cases of reversible lithium neurotoxicity were extracted. Among the 52 cases of reversible lithium neurotoxicity, patients ranged in age from 10 to 80 years and a greater number were female (P = .008). Most patients had affective disorders, schizoaffective disorders, and/or depression (P lithium levels were less than or equal to 1.5 mEq/L (P lithium, underlying brain pathology, abnormal tissue levels, specific diagnostic categories, and elderly populations were some of the precipitating factors reported for reversible lithium neurotoxicity. The preventive measures were also described. Reversible lithium neurotoxicity presents with a certain clinical profile and precipitating factors for which there are appropriate preventive measures. This recognition will help in early diagnosis and prompt treatment of

  13. Parallelization of Reversible Ripple-carry Adders

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Axelsen, Holger Bock

    2009-01-01

    The design of fast arithmetic logic circuits is an important research topic for reversible and quantum computing. A special challenge in this setting is the computation of standard arithmetical functions without the generation of \\emph{garbage}. Here, we present a novel parallelization scheme......{O}(m\\cdot k)$. The underlying mechanisms of the parallelization scheme are formally proven correct. We also show designs for garbage-less reversible comparison circuits. We compare the circuit costs of the resulting ripple-block carry adder with known optimized reversible ripple-carry adders in measures...

  14. Reverse logistics in the Brazilian construction industry.

    Science.gov (United States)

    Nunes, K R A; Mahler, C F; Valle, R A

    2009-09-01

    In Brazil most Construction and Demolition Waste (C&D waste) is not recycled. This situation is expected to change significantly, since new federal regulations oblige municipalities to create and implement sustainable C&D waste management plans which assign an important role to recycling activities. The recycling organizational network and its flows and components are fundamental to C&D waste recycling feasibility. Organizational networks, flows and components involve reverse logistics. The aim of this work is to introduce the concepts of reverse logistics and reverse distribution channel networks and to study the Brazilian C&D waste case.

  15. Time reversibility, computer simulation, and chaos

    CERN Document Server

    Hoover, William Graham

    1999-01-01

    A small army of physicists, chemists, mathematicians, and engineers has joined forces to attack a classic problem, the "reversibility paradox", with modern tools. This book describes their work from the perspective of computer simulation, emphasizing the author's approach to the problem of understanding the compatibility, and even inevitability, of the irreversible second law of thermodynamics with an underlying time-reversible mechanics. Computer simulation has made it possible to probe reversibility from a variety of directions and "chaos theory" or "nonlinear dynamics" has supplied a useful

  16. Performance of the reverse Helmbold universal portfolio

    Science.gov (United States)

    Tan, Choon Peng; Kuang, Kee Seng; Lee, Yap Jia

    2017-04-01

    The universal portfolio is an important investment strategy in a stock market where no stochastic model is assumed for the stock prices. The zero-gradient set of the objective function estimating the next-day portfolio which contains the reverse Kullback-Leibler order-alpha divergence is considered. From the zero-gradient set, the explicit, reverse Helmbold universal portfolio is obtained. The performance of the explicit, reverse Helmbold universal portfolio is studied by running them on some stock-price data sets from the local stock exchange. It is possible to increase the wealth of the investor by using these portfolios in investment.

  17. NARCOSIS AND EMULSION REVERSAL BY INERT GASES

    Science.gov (United States)

    Sears, Dewey F.; Fenn, Wallace O.

    1957-01-01

    Investigations of the effect of high pressures of Na (100 to 130 atmospheres) and of Ar (60 to 80 atmospheres) showed that these gases are effective in reversing the phases of an oil in water emulsion. Nitrous oxide did not cause reversal at pressures as high as 53 atmospheres nor did helium as high as 107 atmospheres. We found CO2 most effective in reversing the emulsions and attributed this to its chemical properties. It is suggested that these observations may help to explain the narcotic effects of inert gases. PMID:13416527

  18. Contextual influences on reverse knowledge transfer

    DEFF Research Database (Denmark)

    Søberg, Peder Veng

    2010-01-01

    Further development of theories about how contextual factors influence the beneficial reverse knowledge transfer from subsidiary to head quarters in disparate national country contexts, is the aim of our study. Earlier studies do not fully capture the different effects national country cultures can....... A proposition model is developed where the dependent variable is beneficial reverse knowledge transfer. The independent variables are: higher relative knowledge level in subsidiaty than in HQ, authority respect, activity fit with contextual learning preference. The conclusion suggest that different contexts...... promote different learning preferences and possibly complementarities may exist between these. Furthermore, double loop learning is not required for beneficial reverse knowledge transfer....

  19. Dynamic Reverse Code Generation for Backward Execution

    DEFF Research Database (Denmark)

    Lee, Jooyong

    2007-01-01

    he need for backward execution in debuggers has been raised a number of times. Backward execution helps a user naturally think backwards and, in turn, easily locate the cause of a bug. Backward execution has been implemented mostly by state-saving or checkpointing, which are inherently not scalable....... In this paper, we present a method to generate reverse code, so that backtracking can be performed by executing reverse code. The novelty of our work is that we generate reverse code on-the-fly, while running a debugger, which makes it possible to apply the method even to debugging multi-threaded programs....

  20. Cognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    De Jesus Moreno Moreno, Maria

    2003-01-01

    Parallel with the development of hypotheses regarding cholinergic involvement in geriatric memory dysfunction, the first attempts to treat patients with Alzheimer's disease (AD) involved the cholinergic-precursor loading approach. Despite encouraging early results, well-controlled clinical trials did not confirm a clinical utility of cholinergic precursors such as choline and lecithin (phosphatidylcholine) in AD. This study assessed the efficacy and tolerability of the cholinergic precursor choline alfoscerate (CA) in the treatment of cognitive impairment due to mild to moderate AD. In this multicenter, double-blind, randomized, placebo-controlled trial, patients affected by mild to moderate dementia of the Alzheimer type were treated with CA (400-mg capsules) or placebo capsules, 3 times daily, for 180 days. Efficacy outcome measures that were assessed at the beginning of the investigation and after 90 and 180 days of treatment included scores of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), the Mini-Mental State Examination (MMSE), the Global Deterioration Scale (GDS), the Alzheimer's Disease Assessment Scale-Behavioral Subscale (ADAS-Behav), all items of the Alzheimer's Disease Assessment Scale (ADAS-Total), and the Clinical Global Impression (CGI) scale. The Global Improvement Scale (GIS) score was assessed after 90 and 180 days of treatment. A total of 261 patients (132 in the CA group, 129 in the placebo group) were enrolled in the study. The mean (SD) age in the CA group was 72.2(7.5) years (range, 60-80 years), and in the placebo group it was 71.7 (7.4) years(range, 60-80 years). The CA group comprised 105 women and 27 men; the placebo group, 94 women and 35 men. The mean decrease in ADAS-Cog score in patients treated with CA was 2.42 points after 90 days of treatment and 3.20 points at the end of the study (day 180) (P vs baseline for both), whereas in patients receiving placebo the mean increase in ADAS-Cog score was 0.36 point

  1. 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.

  2. Thermodynamics and activity coefficients at infinite dilution for organic solutes, water and diols in the ionic liquid choline bis(trifluoromethylsulfonyl)imide

    International Nuclear Information System (INIS)

    Domańska, Urszula; Papis, Paulina; Szydłowski, Jerzy

    2014-01-01

    Graphical abstract: - Highlights: • Measurements of activity coefficients at infinite dilution using GLC. • 63 Solvents including water and 6 diols in the ionic liquid choline bis(trifluoromethylsulfonyl)imide. • High selectivity for thiophene/heptane and pyridine/heptane separation. • The excess thermodynamic functions and the (gas + liquid) partition coefficients were calculated. - Abstract: The activity coefficients at infinite dilution, γ 13 ∞ , for 63 solutes, including alkanes, cycloalkanes, alkenes, alkynes, aromatic hydrocarbons, alcohols, water, thiophene, ethers, ketones, esters, aldehyde, acetonitrile, pyridine and 1-nitropropane and 6 diols in the ionic liquid (IL) choline bis(trifluoromethylsulfonyl)imide, [N 1112OH ][NTf 2 ] were determined by (gas + liquid) chromatography at six temperatures in range of (318.15 to 368.15) K and at three temperatures for diols in the range of (388.15 to 418.15) K. The thermodynamic functions at infinite dilution as partial molar excess Gibbs free energy, ΔG 1 E,∞ , enthalpy ΔH 1 E,∞ , and entropy term T ref ΔS 1 E,∞ were calculated from the experimental γ 13 ∞ values obtained over the temperature range. The density of [N 1112OH ][NTf 2 ] was measured within temperature range (313.15 to 353.15) K. The (gas + liquid) partition coefficient K L was calculated for all solutes. The values of selectivity and capacity for a few separation problems as hexane/benzene, cyclohexane/benzene, heptane/thiophene at T = 328.15 K were calculated from γ 13 ∞ and compared to literature values for similar ionic liquids, N-methyl-2-pyrrolidinone (NMP), and sulfolane. In comparison with the former measured ammonium-based ILs and the morpholinium-based ILs, the [N 1112OH ][NTf 2 ] shows average selectivity for the separation of aromatic hydrocarbons, or sulfur compound from aliphatic hydrocarbons, and very high selectivity for pyridine/heptane separation. New data show that [N 1112OH ][NTf 2 ] IL may be proposed as

  3. 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.

  4. Medical abortion reversal: science and politics meet.

    Science.gov (United States)

    Bhatti, Khadijah Z; Nguyen, Antoinette T; Stuart, Gretchen S

    2018-03-01

    Medical abortion is a safe, effective, and acceptable option for patients seeking an early nonsurgical abortion. In 2014, medical abortion accounted for nearly one third (31%) of all abortions performed in the United States. State-level attempts to restrict reproductive and sexual health have recently included bills that require physicians to inform women that a medical abortion is reversible. In this commentary, we will review the history, current evidence-based regimen, and regulation of medical abortion. We will then examine current proposed and existing abortion reversal legislation. The objective of this commentary is to ensure physicians are armed with rigorous evidence to inform patients, communities, and policy makers about the safety of medical abortion. Furthermore, given the current paucity of evidence for medical abortion reversal, physicians and policy makers can dispel bad science and misinformation and advocate against medical abortion reversal legislation. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The Cigeo project. The Cigeo reversibility

    International Nuclear Information System (INIS)

    2013-10-01

    This publication briefly presents the main aspects of the introduction of reversibility in the design, construction and operation of the industrial centre of deep geological storage (CIGEO) of radioactive wastes. It recalls that this reversibility has been demanded by the public and requested by the French Parliament: the storage must remain reversible during 100 years. The main proposals made by the ANDRA are briefly described: to be able to recover stored parcels (technical arrangements), to choose the planning of a step-by-step storage closure, and to prepare decision and to organise the relay between generations or to decide whether to go on or not. The issue of reversibility financing is also evoked

  6. Time reversibility, computer simulation, algorithms, chaos

    CERN Document Server

    Hoover, William Graham

    2012-01-01

    A small army of physicists, chemists, mathematicians, and engineers has joined forces to attack a classic problem, the "reversibility paradox", with modern tools. This book describes their work from the perspective of computer simulation, emphasizing the author's approach to the problem of understanding the compatibility, and even inevitability, of the irreversible second law of thermodynamics with an underlying time-reversible mechanics. Computer simulation has made it possible to probe reversibility from a variety of directions and "chaos theory" or "nonlinear dynamics" has supplied a useful vocabulary and a set of concepts, which allow a fuller explanation of irreversibility than that available to Boltzmann or to Green, Kubo and Onsager. Clear illustration of concepts is emphasized throughout, and reinforced with a glossary of technical terms from the specialized fields which have been combined here to focus on a common theme. The book begins with a discussion, contrasting the idealized reversibility of ba...

  7. Reversibility of hyperhidrosis post axillary depilatory laser.

    Science.gov (United States)

    Helou, Josiane; Habre, Maya; Soutou, Boutros; Maatouk, Ismael; Ibrahim, Tony; Tomb, Roland

    2014-03-01

    Hyperhidrosis and bromhidrosis were lately reported as novel side effects of laser-assisted removal of axillary hair. The goal of our study was to evaluate the reversibility of these two side effects. An observational, single-center cohort study included over a 30-month screening period 30 patients with newly reported hyperhidrosis and/or bromhidrosis related to axillary depilatory laser. After 26 weeks of follow-up, each patient was assessed for spontaneous reversibility. A 12-week duration treatment with topical aluminum chloride was evaluated in patients with persisting hyperhidrosis. Hyperhidrosis was assessed using the Hyperhidrosis Disease Severity Scale (HDSS). Spontaneous reversibility was observed in 20% of patients. In total, 23 out of 30 patients recovered normal axillary transpiration either spontaneously or after treatment. Mean HDSS score was significantly lower in the treated group. It appears that axillary hyperhidrosis and bromhidrosis, secondary to laser depilation, reverse either spontaneously or after using topical antiperspirant.

  8. Reversal of target-specific oral anticoagulants

    Science.gov (United States)

    Siegal, D.M.; Cuker, Adam

    2014-01-01

    Target-specific oral anticoagulants (TSOACs) provide safe and effective anticoagulation for the prevention and treatment of thrombosis in a variety of clinical settings by interfering with the activity of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban, betrixaban). Although TSOACs have practical advantages over vitamin K antagonists (VKAs), there are currently no antidotes to reverse their anticoagulant effect. Herein we summarize the available evidence for TSOAC reversal using nonspecific and specific reversal agents. We discuss important limitations of existing evidence, which is derived from studies in human volunteers, animal models and in vitro experiments. Studies evaluat