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Sample records for fp prostanoid receptors

  1. Prostanoid Receptors Involved in Regulation of the Beating Rate of Neonatal Rat Cardiomyocytes

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    Mechiche, Hakima; Grassin-Delyle, Stanislas; Robinet, Arnaud; Nazeyrollas, Pierre; Devillier, Philippe

    2012-01-01

    Although prostanoids are known to be involved in regulation of the spontaneous beating rate of cultured neonatal rat cardiomyocytes, the various subtypes of prostanoid receptors have not been investigated in detail. In our experiments, prostaglandin (PG)F2α and prostanoid FP receptor agonists (fluprostenol, latanoprost and cloprostenol) produced a decrease in the beating rate. Two prostanoid IP receptor agonists (iloprost and beraprost) induced first a marked drop in the beating rate and then definitive abrogation of beating. In contrast, the prostanoid DP receptor agonists (PGD2 and BW245C) and TP receptor agonists (U-46619) produced increases in the beating rate. Sulprostone (a prostanoid EP1 and EP3 receptor agonist) induced marked increases in the beating rate, which were suppressed by SC-19220 (a selective prostanoid EP1 antagonist). Butaprost (a selective prostanoid EP2 receptor agonist), misoprostol (a prostanoid EP2 and EP3 receptor agonist), 11-deoxy-PGE1 (a prostanoid EP2, EP3 and EP4 receptor agonist) did not alter the beating rate. Our results strongly suggest that prostanoid EP1 receptors are involved in positive regulation of the beating rate. Prostanoid EP1 receptor expression was confirmed by western blotting with a selective antibody. Hence, neonatal rat cardiomyocytes express both prostanoid IP and FP receptors (which negatively regulate the spontaneous beating rate) and prostanoid TP, DP1 and EP1 receptors (which positively regulate the spontaneous beating rate). PMID:22984630

  2. Expression of prostanoid receptors in human ductus arteriosus

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    Leonhardt, Andreas; Glaser, Alexander; Wegmann, Markus; Schranz, Dietmar; Seyberth, Hannsjörg; Nüsing, Rolf

    2003-01-01

    Prostaglandins play a major role in maintaining ductal patency in utero. Ductal tone is regulated by both locally released and circulating vasodilatory prostaglandins. In infants with ductus arteriosus-dependent congenital heart disease, ductal patency is maintained by intravenous administration of prostaglandin (PG) E1. Little information is available regarding the expression of prostaglandin receptors in man. By means of RT–PCR and immunohistochemistry we studied the expression of the PGI2 receptor (IP), the four different PGE2 receptors (EP1, EP2, EP3 and EP4), and the receptors for thromboxane (Tx) A2 (TP), PGD2 (DP) and PGF2α (FP) in the ductus arteriosus of three newborn infants with ductus arteriosus-dependent congenital heart disease and intravenous infusion of PGE1 and of one 8 month old child with a patent ductus arteriosus. The EP3, EP4, FP, IP and TP receptor were markedly expressed at the mRNA and protein level, whereas the EP2 receptor was weakly expressed and the EP1 receptor was detected in two out of four tissue specimens only. The DP receptor was not detected in any of the samples. The most pronounced expression, which was located in the media of the ductus arteriosus, was observed for the EP4 and TP receptors followed by IP and FP receptor protein. These data indicate that ductal patency during the infusion of PGE1 in infants with ductus arteriosus-dependent congenital heart disease might be mediated by the EP4 and IP receptor. The data further suggest that a heterogeneous population of prostanoid receptors may contribute to the regulation of ductus arteriosus tone in humans. PMID:12598419

  3. Prostanoid receptors as possible targets for anti-allergic drugs: recent advances in prostanoids on allergy and immunology.

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    Honda, Tetsuya; Tokura, Yoshiki; Miyachi, Yoshiki; Kabashima, Kenji

    2010-12-01

    Prostanoids, consisting of prostaglandins and thromboxane, are cyclooxygenase metabolites of arachidonic acid released in various pathophysiological conditions which exert a range of actions mediated through their respective receptors expressed on target cells. Although it has been difficult to analyze the physiological role of prostanoids, recent developments in both the disruption of the respective gene and receptor selective compounds have enabled us to investigate the physiological roles for each receptor. It has been demonstrated that each prostanoid receptor has multiple functions, and that their expression is regulated in a context-dependent manner that sometimes results in opposite, excitatory and inhibitory, outcomes. The balance of prostanoid production and receptor expression has been revealed to be important for homeostasis of the human body. Here, we review new findings on the roles of prostanoids in allergic and immune diseases, focusing on contact dermatitis, atopic dermatitis, asthma, rheumatoid arthritis, and encephalomyelitis, and also discuss the clinical potentials of receptor-selective drugs.

  4. Prostaglandin Receptor Signaling in Disease

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    Toshiyuki Matsuoka

    2007-01-01

    Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

  5. Role of the ERC motif in the proximal part of the second intracellular loop and the C-terminal domain of the human prostaglandin F2alpha receptor (hFP-R) in G-protein coupling control.

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    Pathe-Neuschäfer-Rube, Andrea; Neuschäfer-Rube, Frank; Püschel, Gerhard P

    2005-05-15

    The human FP-R (F2alpha prostaglandin receptor) is a Gq-coupled heptahelical ectoreceptor, which is of significant medical interest, since it is a potential target for the treatment of glaucoma and preterm labour. On agonist exposure, it mediates an increase in intracellular inositol phosphate formation. Little is known about the structures that govern the agonist-dependent receptor activation. In other prostanoid receptors, the C-terminal domain has been inferred in the control of agonist-dependent receptor activation. A DRY motif at the beginning of the second intracellular loop is highly conserved throughout the G-protein-coupled receptor family and appears to be crucial for controlling agonist-dependent receptor activation. It is replaced by an ERC motif in the FP-R and no evidence for the relevance of this motif in ligand-dependent activation of prostanoid receptors has been provided so far. The aim of the present study was to elucidate the potential role of the C-terminal domain and the ERC motif in agonist-controlled intracellular signalling in FP-R mutants generated by site-directed mutagenesis. It was found that substitution of the acidic Glu(132) in the ERC motif by a threonine residue led to full constitutive activation, whereas truncation of the receptor's C-terminal domain led to partial constitutive activation of all three intracellular signal pathways that had previously been shown to be activated by the FP-R, i.e. inositol trisphosphate formation, focal adhesion kinase activation and T-cell factor signalling. Inositol trisphosphate formation and focal adhesion kinase phosphorylation were further enhanced by ligand binding in cells expressing the truncation mutant but not the E132T (Glu132-->Thr) mutant. Thus C-terminal truncation appeared to result in a receptor with partial constitutive activation, whereas substitution of Glu132 by threonine apparently resulted in a receptor with full constitutive activity.

  6. Pharmacology of functional endogenous IP prostanoid receptors in NCB-20 cells: comparison with binding data from human platelets.

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    Crider, J Y; Xu, S X; Sharif, N A

    2001-01-01

    The objective of these studies was to characterize the effects of a broad range of prostanoid agonists upon the stimulation of cAMP production in National Cancer Bank (NCB-20; mouse neuroblastoma/hamster brain hybridoma) cells. The pharmacology of these functional responses in NCB-20 cells was compared with that of the classic endogenous IP receptor present on human platelets using [3H]-iloprost binding techniques. In both assay systems, agonists from the IP prostanoid class exhibited the highest affinities and functional potencies. Specific prostanoids exhibited the following rank order of potency (EC50 +/- SEM) in stimulating cAMP production in the NCB-20 cells: carbaprostacyclin (4.3 +/- 0.9 nM) = PGI2 (6.6 +/-1.5 nM) > iloprost (75+/-13 nM) > 11-deoxy PGE, (378+/-138 nM) > misoprostol (1,243+/-48) > PGE2 (3020+/-700 nM) > ZK-118182 (7265+/-455 nM). Iloprost wasthe most potent compound in the human platelet binding assay while prostanoidsfromthe DPand EP receptor classes showed modest affinity. These studies provide functional and binding information for a broad range of both natural and synthetic prostanoid receptor ligands at the endogenous IP receptor in two different cell types.

  7. Prostanoid receptor EP2 as a therapeutic target.

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    Ganesh, Thota

    2014-06-12

    Cycoloxygenase-2 (COX-2) induction is prevalent in a variety of (brain and peripheral) injury models where COX-2 levels correlate with disease progression. Thus, COX-2 has been widely explored for anti-inflammatory therapy with COX-2 inhibitors, which proved to be effective in reducing the pain and inflammation in patients with arthritis and menstrual cramps, but they have not provided any benefit to patients with chronic inflammatory neurodegenerative disease. Recently, two COX-2 drugs, rofecoxib and valdecoxib, were withdrawn from the United States market due to cardiovascular side effects. Thus, future anti-inflammatory therapy could be targeted through a specific prostanoid receptor downstream of COX-2. The PGE2 receptor EP2 is emerging as a pro-inflammatory target in a variety of CNS and peripheral diseases. Here we highlight the latest developments on the role of EP2 in diseases, mechanism of activation, and small molecule discovery targeted either to enhance or to block the function of this receptor.

  8. Intermittent hypoxia alters dose dependent caffeine effects on renal prostanoids and receptors in neonatal rats.

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    Beharry, Kay D; Cai, Charles L; Soontarapornchai, Kultida; Ahmad, Taimur; Valencia, Gloria B; Aranda, Jacob V

    2018-01-01

    Caffeine, one of the most commonly prescribed drugs in preterm neonates, is given in standard or suprapharmacologic doses. Although known as a diuretic, its effects in the neonatal kidneys are not well studied. We tested the hypothesis that neonatal intermittent hypoxia (IH) and high caffeine doses (HCD) alter renal regulators of vasomotor tone and water balance. Newborn rats were randomized to room air, hyperoxia, or IH and treated with standard or high caffeine doses; or placebo saline. Renal prostanoids; histopathology; and cyclooxygenase (COX), prostanoid receptor, and aquaporin (AQP) immunoreactivity were determined. HCD in IH caused severe pathological changes in the glomeruli and proximal tubules, consistent with acute kidney injury. This was associated with reductions in anthropometric growth, PGI 2, and IP, DP, and AQP-4 immunoreactivity, well as a robust increase in COX-2, suggesting that the use of HCD should be avoided in preterm infants who experience frequent IH episodes. Published by Elsevier Inc.

  9. Prostaglandin D2 inhibits airway dendritic cell migration and function in steady state conditions by selective activation of the D prostanoid receptor 1

    NARCIS (Netherlands)

    H. Hammad (Hamida); H.J. de Heer; T. Soullié (Thomas); H.C. Hoogsteden (Henk); F. Trottein; B.N.M. Lambrecht (Bart)

    2003-01-01

    textabstractPGD(2) is the major mediator released by mast cells during allergic responses, and it acts through two different receptors, the D prostanoid receptor 1 (DP1) and DP2, also known as CRTH2. Recently, it has been shown that PGD(2) inhibits the migration of epidermal

  10. Why does the agonist [18F]FP-TZTP bind preferentially to the M2 muscarinic receptor?

    International Nuclear Information System (INIS)

    Ravasi, L.; Kiesewetter, D.O.; Shimoji, K.; Lucignani, G.; Eckelman, W.C.

    2006-01-01

    Preferential binding of FP-TZTP at the M 2 receptor in vivo led to investigation of [ 18 F]FP-TZTP as a potential PET tracer for Alzheimer's disease, in which a substantial reduction of M 2 receptors has been observed in autopsy studies. We hereby investigated in vitro the FP-TZTP behavior to further elucidate the properties of FP-TZTP that lead to its M 2 selectivity. Chinese hamster ovarian cells expressing the five subtypes of human muscarinic receptor as well as the wild type were harvested in culture to assess equilibrium binding. Specific binding was calculated by subtraction of non-specific binding from total binding. Internal specific binding was calculated by subtraction of external specific binding from the total specific binding. Saturation assays were also performed to calculate B max , K i , and IC 50 . In addition, equilibrium binding and dissociation kinetic studies were performed on rat brain tissue. Selected regions of interest were drawn on the digital autoradiograms and [ 18 F]FP-TZTP off-rates were determined by measurement of the rate of release into a buffer solution of [ 18 F]FP-TZTP from slide-bound cells that had been preincubated with [ 18 F]FP-TZTP. At equilibrium in vitro, M 2 subtype selectivity of [ 18 F]FP-TZTP was not evident. We demonstrated that ATP-dependent mechanisms are not responsible for FP-TZTP M 2 selectivity. In vitro off-rate studies from rat brain tissue showed that the off-rate of FP-TZTP varied with the percentage of M 2 subtype in the tissue region. The slower dissociation kinetics of FP-TZTP from M 2 receptors compared with the four other muscarinic receptor subtypes may be a factor in its M 2 selectivity. (orig.)

  11. Prostaglandin F2α–F-Prostanoid Receptor Signalling Promotes Neutrophil Chemotaxis via Chemokine (CXC motif) Ligand-1 in Endometrial Adenocarcinoma

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    Wallace, Alison E; Sales, Kurt J; Catalano, Roberto D; Anderson, Richard A; Williams, Alistair RW; Wilson, Martin R; Schwarze, Jurgen; Wang, Hongwei; Rossi, Adriano G; Jabbour, Henry N

    2009-01-01

    The prostaglandin F2α (PGF2α) receptor (FP) is elevated in endometrial adenocarcinoma. This study found that PGF2α signalling via FP regulates expression of chemokine (C-X-C motif) ligand 1 (CXCL1) in endometrial adenocarcinoma cells. Expression of CXCL1 and its receptor, CXCR2, are elevated in cancer tissue as compared to normal endometrium and localised to glandular epithelium, endothelium and stroma. Treatment of Ishikawa cells stably transfected with the FP receptor (FPS cells) with 100nM PGF2α increased CXCL1 promoter activity, mRNA and protein expression, and these effects were abolished by co-treatment of cells with FP antagonist or chemical inhibitors of Gq, EGFR and ERK. Similarly, CXCL1 was elevated in response to 100 nM PGF2α in endometrial adenocarcinoma explant tissue. CXCL1 is a potent neutrophil chemoattractant. The expression of CXCR2 colocalised to neutrophils in endometrial adenocarcinoma and increased neutrophils were present in endometrial adenocarcinoma compared with normal endometrium. Conditioned media from PGF2α-treated FPS cells stimulated neutrophil chemotaxis which could be abolished by CXCL1 protein immunoneutralisation of the conditioned media or antagonism of CXCR2. Finally, xenograft tumours in nude mice arising from inoculation with FPS cells showed increased neutrophil infiltration compared to tumours arising from wild-type cells or following treatment of mice bearing FPS tumours with CXCL1-neutralising antibody. In conclusion, our results demonstrate a novel PGF2α-FP pathway that may regulate the inflammatory microenvironment in endometrial adenocarcinoma via neutrophil chemotaxis. PMID:19549892

  12. Prostaglandins in the kidney: developments since Y2K.

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    Nasrallah, Rania; Clark, Jordan; Hébert, Richard L

    2007-10-01

    There are five major PGs (prostaglandins/prostanoids) produced from arachidonic acid via the COX (cyclo-oxygenase) pathway: PGE(2), PGI(2) (prostacyclin), PGD(2), PGF(2alpha) and TXA(2) (thromboxane A(2)). They exert many biological effects through specific G-protein-coupled membrane receptors, namely EP (PGE(2) receptor), IP (PGI(2) receptor), DP (PGD(2) receptor), FP (PGF(2alpha) receptor) and TP (TXA(2) receptor) respectively. PGs are implicated in physiological and pathological processes in all major organ systems, including cardiovascular function, gastrointestinal responses, reproductive processes, renal effects etc. This review highlights recent insights into the role of each prostanoid in regulating various aspects of renal function, including haemodynamics, renin secretion, growth responses, tubular transport processes and cell fate. A thorough review of the literature since Y2K (year 2000) is provided, with a general overview of PGs and their synthesis enzymes, and then specific considerations of each PG/prostanoid receptor system in the kidney.

  13. Prostanoids modulate inflammation and alloimmune responses during graft rejection

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    P.N. Rocha

    2005-12-01

    Full Text Available Acute rejection of a transplanted organ is characterized by intense inflammation within the graft. Yet, for many years transplant researchers have overlooked the role of classic mediators of inflammation such as prostaglandins and thromboxane (prostanoids in alloimmune responses. It has been demonstrated that local production of prostanoids within the allograft is increased during an episode of acute rejection and that these molecules are able to interfere with graft function by modulating vascular tone, capillary permeability, and platelet aggregation. Experimental data also suggest that prostanoids may participate in alloimmune responses by directly modulating T lymphocyte and antigen-presenting cell function. In the present paper, we provide a brief overview of the alloimmune response, of prostanoid biology, and discuss the available evidence for the role of prostaglandin E2 and thromboxane A2 in graft rejection.

  14. NO and prostanoids blunt endothelin-mediated coronary vasoconstrictor influence in exercising swine

    NARCIS (Netherlands)

    D. Merkus (Daphne); O. Sorop (Oana); B. Houweling (Birgit); F. Boomsma (Frans); A.H. van den Meiracker (Anton); D.J.G.M. Duncker (Dirk)

    2006-01-01

    textabstractWithdrawal of the endothelin (ET)-mediated vasoconstrictor influence contributes to metabolic coronary vasodilation during exercise. Because production of nitric oxide (NO) and prostanoids increases with increasing shear stress and because NO and prostanoids are able to modify the

  15. Prostanoid-dependent bladder pain caused by proteinase-activated receptor-2 activation in mice: Involvement of TRPV1 and T-type Ca2+ channels

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    Maho Tsubota

    2018-01-01

    Full Text Available We studied the pronociceptive role of proteinase-activated receptor-2 (PAR2 in mouse bladder. In female mice, intravesical infusion of the PAR2-activating peptide, SLIGRL-amide (SL, caused delayed mechanical hypersensitivity in the lower abdomen, namely ‘referred hyperalgesia’, 6–24 h after the administration. The PAR2-triggered referred hyperalgesia was prevented by indomethacin or a selective TRPV1 blocker, and restored by a T-type Ca2+ channel blocker. In human urothelial T24 cells, SL caused delayed prostaglandin E2 production and COX-2 upregulation. Our data suggest that luminal PAR2 stimulation in the bladder causes prostanoid-dependent referred hyperalgesia in mice, which involves the activation of TRPV1 and T-type Ca2+ channels.

  16. Expression of the TPα and TPβ isoforms of the thromboxane prostanoid receptor (TP) in prostate cancer: clinical significance and diagnostic potential.

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    Mulvaney, Eamon P; Shilling, Christine; Eivers, Sarah B; Perry, Antoinette S; Bjartell, Anders; Kay, Elaine W; Watson, R William; Kinsella, B Therese

    2016-11-08

    The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPα and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown.This study evaluated expression of the TPα and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa). Expression of TPβ was significantly increased in PCa relative to benign tissue and strongly correlated with increasing Gleason grade. Furthermore, higher TPβ expression was associated with increased risk of biochemical recurrence (BCR) and significantly shorter disease-free survival time in patients post-surgery. While TPα was more variably expressed than TPβ in PCa, increased/high TPα expression within the tumour also trended toward increased BCR and shorter disease-free survival time. Comparative genomic CpG DNA methylation analysis revealed substantial differences in the extent of methylation of the promoter regions of the TBXA2R that specifically regulate expression of TPα and TPβ, respectively, both in benign prostate and in clinically-derived tissue representative of precursor lesions and progressive stages of PCa. Collectively, TPα and TPβ expression is differentially regulated both in the benign and tumourigenic prostate, and coincides with clinical pathology and altered CpG methylation of the TBXA2R gene. Analysis of TPβ, or a combination of TPα/TPβ, expression levels may have significant clinical potential as a diagnostic biomarker and predictor of PCa disease recurrence.

  17. Prostaglandin E2 Prevents Hyperosmolar-Induced Human Mast Cell Activation through Prostanoid Receptors EP2 and EP4

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    Torres-Atencio, Ivonne; Ainsua-Enrich, Erola; de Mora, Fernando; Picado, César; Martín, Margarita

    2014-01-01

    Background Mast cells play a critical role in allergic and inflammatory diseases, including exercise-induced bronchoconstriction (EIB) in asthma. The mechanism underlying EIB is probably related to increased airway fluid osmolarity that activates mast cells to the release inflammatory mediators. These mediators then act on bronchial smooth muscle to cause bronchoconstriction. In parallel, protective substances such as prostaglandin E2 (PGE2) are probably also released and could explain the refractory period observed in patients with EIB. Objective This study aimed to evaluate the protective effect of PGE2 on osmotically activated mast cells, as a model of exercise-induced bronchoconstriction. Methods We used LAD2, HMC-1, CD34-positive, and human lung mast cell lines. Cells underwent a mannitol challenge, and the effects of PGE2 and prostanoid receptor (EP) antagonists for EP1–4 were assayed on the activated mast cells. Beta-hexosaminidase release, protein phosphorylation, and calcium mobilization were assessed. Results Mannitol both induced mast cell degranulation and activated phosphatidyl inositide 3-kinase and mitogen-activated protein kinase (MAPK) pathways, thereby causing de novo eicosanoid and cytokine synthesis. The addition of PGE2 significantly reduced mannitol-induced degranulation through EP2 and EP4 receptors, as measured by beta-hexosaminidase release, and consequently calcium influx. Extracellular-signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38 phosphorylation were diminished when compared with mannitol activation alone. Conclusions Our data show a protective role for the PGE2 receptors EP2 and EP4 following osmotic changes, through the reduction of human mast cell activity caused by calcium influx impairment and MAP kinase inhibition. PMID:25329458

  18. Anti-Inflammatory Prostanoids: Focus on the Interactions between Electrophile Signaling and Resolution of Inflammation

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    Beatriz Díez-Dacal

    2010-01-01

    Full Text Available Prostanoids are products of cyclooxygenase biosynthetic pathways and constitute a family of lipidic mediators of widely diverse structures and biological actions. Besides their known proinflammatory role, numerous works have revealed the anti-inflammatory effects of various prostanoids and established their role in the resolution of inflammation. Among these, prostaglandins with cyclopentenone structure (cyPG are electrophilic lipids that may act through various mechanisms, including the activation of nuclear and membrane receptors and, importantly, direct addition to protein cysteine residues and modification of protein function. Due to their ability to influence cysteine modification–mediated signaling, cyPG may play a critical role in the interplay between redox and inflammatory signaling pathways. Moreover, cellular redox status modulates cyPG addition to proteins; thus, a reciprocal regulation exists between these two factors. After initial controversy, it is becoming clear that endogenous cyPG are generated at concentrations sufficient to promote inflammatory resolution. As for other prostanoids, cyPG effects are highly dependent on context factors and they may exert pro- or anti-inflammatory actions in a cell type–dependent manner, or even biphasic or dual actions in a given cell type or tissue. In light of the growing number of cyPG protein targets identified, cyPG resemble other pleiotropic mediators acting through protein modification. However, their complex structure results in an inter- and intramolecular selectivity of the residues being modified, thus opening the way for structure-activity and drug discovery studies. Detailed characterization of cyPG interactions with cellular proteins will help us to understand their mechanism of action fully and establish their therapeutic potential in inflammation.

  19. Mortality in Pulmonary Arterial Hypertension Patients Treated with Continuous Prostanoids.

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    Bartolome, S D; Sood, N; Shah, T S; Styrvoky, K; Torres, F T; Chin, K M

    2018-04-18

    Parenteral prostanoids are considered the treatment of choice for patients with severe pulmonary arterial hypertension (PAH). Prognostic studies for patients treated in the modern era are limited. In this retrospective cohort study, patients initiating IV epoprostenol or IV or SC treprostinil therapy for PAH from 2007-2016 at UT Southwestern, Dallas, TX and Ohio State University, Columbus, OH were included. Transplant-free survival was assessed from the time of IV/SC initiation and from the time of first follow-up. The utility of traditional prognostic measures was assessed using categories (lower, intermediate, higher risk) recommended in the 2015 ESC/ERS guidelines for functional class (FC), six-minute walk distance (6MWD), brain natriuretic peptide (BNP) or N-terminal BNP (NT-proBNP) level and hemodynamic results. Patients with group 1 PAH receiving IV epoprostenol (N=132), IV treprostinil (N=25) or SC treprostinil (N=38) were included. Survival from IV/SC prostanoid initiation was 84%, 77% and 67% at one, two and three years. Follow-up assessment was performed after a minimum of 90 days therapy (mean 356±247 days) in 163 patients. After treatment with an IV/SC prostanoid, better FC, 6MWD, BNP / NT-proBNP and SVO2 but not cardiac index associated with survival, as did the total number of lower-risk and higher-risk findings. Having zero lower risk or two or more higher risk findings was associated with particularly poor outcomes. In PAH patients receiving treatment with a parenteral prostanoid, survival associates significantly with the number of guideline recommended lower-risk and higher-risk criteria achieved at first follow-up. Copyright © 2018. Published by Elsevier Inc.

  20. Comparison of MEK/ERK pathway inhibitors on the upregulation of vascular G-protein coupled receptors in rat cerebral arteries

    DEFF Research Database (Denmark)

    Sandhu, Hardip; Ansar, Saema; Edvinsson, Lars

    2010-01-01

    on translational level and increased respective contractions. The prostanoid TP receptor mediated contraction curve was left-wards shifted by organ culture. Organ culture was associated with elevated pERK1/2 in the vascular smooth muscle cells: the MEK1/2 inhibitor U0126 attenuated the endothelin ET(B) receptor...... mediated contraction at post-translational level or by changing the receptor affinities. The serotonin 5-HT(1B) receptor and prostanoid TP receptor mediated contractions were abolished by U0126. Administration of U0126 6h after start of incubation blocked the receptor upregulation. In conclusion, MEK...

  1. The Vasopressin Type-2 Receptor and Prostaglandin Receptors EP2 and EP4 can Increase Aquaporin-2 Plasma Membrane Targeting Through a cAMP Independent Pathway

    DEFF Research Database (Denmark)

    Olesen, Emma Tina Bisgaard; Moeller, Hanne Bjerregaard; Assentoft, Mette

    2016-01-01

    Apical membrane targeting of the collecting duct water channel aquaporin-2 (AQP2) is essential for body water balance. As this event is regulated by Gs coupled 7-transmembrane receptors such as the vasopressin type 2 receptor (V2R) and the prostanoid receptors EP2 and EP4, it is believed to be c...

  2. The prostaglandin EP1 receptor potentiates kainate receptor activation via a protein kinase C pathway and exacerbates status epilepticus

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    Rojas, Asheebo; Gueorguieva, Paoula; Lelutiu, Nadia; Quan, Yi; Shaw, Renee; Dingledine, Raymond

    2014-01-01

    Prostaglandin E2 (PGE2) regulates membrane excitability, synaptic transmission, plasticity, and neuronal survival. The consequences of PGE2 release following seizures has been the subject of much study. Here we demonstrate that the prostaglandin E2 receptor 1 (EP1, or Ptger1) modulates native kainate receptors, a family of ionotropic glutamate receptors widely expressed throughout the central nervous system. Global ablation of the EP1 gene in mice (EP1-KO) had no effect on seizure threshold after kainate injection but reduced the likelihood to enter status epilepticus. EP1-KO mice that did experience typical status epilepticus had reduced hippocampal neurodegeneration and a blunted inflammatory response. Further studies with native prostanoid and kainate receptors in cultured cortical neurons, as well as with recombinant prostanoid and kainate receptors expressed in Xenopus oocytes, demonstrated that EP1 receptor activation potentiates heteromeric but not homomeric kainate receptors via a second messenger cascade involving phospholipase C, calcium and protein kinase C. Three critical GluK5 C-terminal serines underlie the potentiation of the GluK2/GluK5 receptor by EP1 activation. Taken together, these results indicate that EP1 receptor activation during seizures, through a protein kinase C pathway, increases the probability of kainic acid induced status epilepticus, and independently promotes hippocampal neurodegeneration and a broad inflammatory response. PMID:24952362

  3. Comparison of MEK/ERK pathway inhibitors on the upregulation of vascular G-protein coupled receptors in rat cerebral arteries

    DEFF Research Database (Denmark)

    Sandhu, Hardip; Ansar, Saema; Edvinsson, Lars

    2010-01-01

    on translational level and increased respective contractions. The prostanoid TP receptor mediated contraction curve was left-wards shifted by organ culture. Organ culture was associated with elevated pERK1/2 in the vascular smooth muscle cells: the MEK1/2 inhibitor U0126 attenuated the endothelin ET(B) receptor......Organ culture is an in vitro method for investigating cellular mechanisms involved in upregulation of vasocontractile G-protein coupled receptors. We hypothesize that mitogen-activated-protein kinase (MEK) and/or extracellular-signal-regulated kinase (ERK) specific inhibitors will attenuate the G......), prostanoid TP receptor, and angiotensin II receptor type 1 and type 2 were investigated. Results were verified by measurement of mRNA with real time PCR and by protein immunohistochemistry. Organ culture induced transcriptional upregulation of endothelin ET(B) receptor and of serotonin 5-HT(1B) receptor...

  4. Diagnostic value of asymmetric striatal D2 receptor upregulation in Parkinson's disease: an [123I]IBZM and [123I]FP-CIT SPECT study

    International Nuclear Information System (INIS)

    Verstappen, C.C.P.; Bloem, B.R.; Haaxma, C.A.; Horstink, M.W.I.M.; Oyen, W.J.G.

    2007-01-01

    Striatal postsynaptic D 2 receptors in Parkinson's disease (PD) are thought to be upregulated in the first years of the disease, especially contralateral to the clinically most affected side. The aim of this study was to evaluate whether the highest striatal D 2 binding is found contralateral to the most affected side in PD, and whether this upregulation can be used as a diagnostic tool. Cross-sectional survey was undertaken of 81 patients with clinically asymmetric PD, without antiparkinsonian drugs and with a disease duration of ≤5 years and 26 age-matched controls. Striatal D 2 binding was assessed with [ 123 I]IBZM SPECT, and severity of the presynaptic dopaminergic lesion with [ 123 I]FP-CIT SPECT. The mean striato-occipital ratio of [ 123 I]IBZM binding was significantly higher in PD patients (1.56 ±0.09) than in controls (1.53 ±0.06). In PD patients, higher values were found contralateral to the clinically most affected side (1.57 ±0.09 vs 1.55 ±0.10 ipsilaterally), suggesting D 2 receptor upregulation, and the reverse was seen using [ 123 I]FP-CIT SPECT. However, on an individual basis only 56% of PD patients showed this upregulation. Our study confirms asymmetric D 2 receptor upregulation in PD. However, the sensitivity of contralateral higher striatal [ 123 I]IBZM binding is only 56%. Therefore, the presence of contralateral higher striatal IBZM binding has insufficient diagnostic accuracy for PD, and PD cannot be excluded in patients with parkinsonism and no contralateral upregulation of D 2 receptors, assessed with [ 123 I]IBZM SPECT. (orig.)

  5. Bibliometric performance analysis of publications from Danish researchers linked to FP6 and FP7

    DEFF Research Database (Denmark)

    Schneider, Jesper Wiborg; Ryan, Thomas Kjeldager

    2015-01-01

    This chapter presents an analysis29 of the impact of Danish scientific publications that were the result of FP6 or FP7 funding. The purpose is to gain an insight into the scientific impact researchers can achieve when participating in FP6 and FP7. In order to look at impact we have identified cit...... Foundation (DNRF) and the Danish Council for Independent Research (DFF). Finally the analyses also explore the impact at the level of programme themes under FP6 and FP7....

  6. IL-6 Overexpression in ERG-Positive Prostate Cancer Is Mediated by Prostaglandin Receptor EP2.

    Science.gov (United States)

    Merz, Constanze; von Mässenhausen, Anne; Queisser, Angela; Vogel, Wenzel; Andrén, Ove; Kirfel, Jutta; Duensing, Stefan; Perner, Sven; Nowak, Michael

    2016-04-01

    Prostate cancer is the most diagnosed cancer in men and multiple risk factors and genetic alterations have been described. The TMPRSS2-ERG fusion event and the overexpression of the transcription factor ERG are present in approximately 50% of all prostate cancer patients, however, the clinical outcome is still controversial. Prostate tumors produce various soluble factors, including the pleiotropic cytokine IL-6, regulating cellular processes such as proliferation and metastatic segregation. Here, we used prostatectomy samples in a tissue microarray format and analyzed the co-expression and the clinicopathologic data of ERG and IL-6 using immunohistochemical double staining and correlated the read-out with clinicopathologic data. Expression of ERG and IL-6 correlated strongly in prostate tissue samples. Forced expression of ERG in prostate tumor cell lines resulted in significantly increased secretion of IL-6, whereas the down-regulation of ERG decreased IL-6 secretion. By dissecting the underlying mechanism in prostate tumor cell lines we show the ERG-mediated up-regulation of the prostanoid receptors EP2 and EP3. The prostanoid receptor EP2 was overexpressed in human prostate cancer tissue. Furthermore, the proliferation rate and IL-6 secretion in DU145 cells was reduced after treatment with EP2-receptor antagonist. Collectively, our study shows that the expression of ERG in prostate cancer is linked to the expression of IL-6 mediated by the prostanoid receptor EP2. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. An improved radiosynthesis of the muscarinic M2 radiopharmaceutical, [18F]FP-TZTP

    International Nuclear Information System (INIS)

    Oosten, Erik M. van; Wilson, Alan A.; Stephenson, Karin A.; Mamo, David C.; Pollock, Bruce G.; Mulsant, Benoit H.; Yudin, Andrei K.; Houle, Sylvain; Vasdev, Neil

    2009-01-01

    The radioligand 3-(4-(3-[ 18 F]fluoropropylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5, 6-tetrahydropyridine ([ 18 F]FP-TZTP) is an agonist with specificity towards subtype 2 of muscarinic acetylcholine (M2) receptors. It is currently the only radiotracer available for imaging M2 receptors in human subjects with positron emission tomography. The present study reports on an improved method for the synthesis of [ 18 F]FP-TZTP, automated using a GE TRACERlab TM FX FN radiosynthesis module. A key facet was the use of a new precursor, 3-(4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazol-3-ylthio) propyl 4-methylbenzenesulfonate. The precursor was fluorinated via nucleophilic displacement of the tosyloxy group by potassium cryptand [ 18 F]fluoride (K[ 18 F]/K 222 ) in CH 3 CN at 80 deg. C for 5 min, and purified by HPLC. Formulated [ 18 F]FP-TZTP was prepared in an uncorrected radiochemical yield of 29±4%, with a specific activity of 138±41 GBq/μmol (3732±1109 mCi/μmol) at the end of synthesis (35 min; n=3). This methodology offers higher yields, faster synthesis times, an optimized precursor, and simpler automation than previously reported

  8. Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors.

    Science.gov (United States)

    Tunaru, Sorin; Althoff, Till F; Nüsing, Rolf M; Diener, Martin; Offermanns, Stefan

    2012-06-05

    Castor oil is one of the oldest drugs. When given orally, it has a laxative effect and induces labor in pregnant females. The effects of castor oil are mediated by ricinoleic acid, a hydroxylated fatty acid released from castor oil by intestinal lipases. Despite the wide-spread use of castor oil in conventional and folk medicine, the molecular mechanism by which ricinoleic acid acts remains unknown. Here we show that the EP(3) prostanoid receptor is specifically activated by ricinoleic acid and that it mediates the pharmacological effects of castor oil. In mice lacking EP(3) receptors, the laxative effect and the uterus contraction induced via ricinoleic acid are absent. Although a conditional deletion of the EP(3) receptor gene in intestinal epithelial cells did not affect castor oil-induced diarrhea, mice lacking EP(3) receptors only in smooth-muscle cells were unresponsive to this drug. Thus, the castor oil metabolite ricinoleic acid activates intestinal and uterine smooth-muscle cells via EP(3) prostanoid receptors. These findings identify the cellular and molecular mechanism underlying the pharmacological effects of castor oil and indicate a role of the EP(3) receptor as a target to induce laxative effects.

  9. Uridine Adenosine Tetraphosphate-Induced Coronary Relaxation Is Blunted in Swine With Pressure Overload: A Role for Vasoconstrictor Prostanoids.

    Science.gov (United States)

    Zhou, Zhichao; Lankhuizen, Inge M; van Beusekom, Heleen M; Cheng, Caroline; Duncker, Dirk J; Merkus, Daphne

    2018-01-01

    Plasma levels of the vasoactive substance uridine adenosine tetraphosphate (Up 4 A) are elevated in hypertensive patients and Up 4 A-induced vascular contraction is exacerbated in various arteries isolated from hypertensive animals, suggesting a potential role of Up 4 A in development of hypertension. We previously demonstrated that Up 4 A produced potent and partially endothelium-dependent relaxation in the porcine coronary microvasculature. Since pressure-overload is accompanied by structural abnormalities in the coronary microvasculature as well as by endothelial dysfunction, we hypothesized that pressure-overload blunts the coronary vasodilator response to Up 4 A, and that the involvement of purinergic receptors and endothelium-derived factors is altered. The effects of Up 4 A were investigated using wire-myography in isolated coronary small arteries from Sham-operated swine and swine with prolonged (8 weeks) pressure overload of the left ventricle induced by aortic banding (AoB). Expression of purinergic receptors and endothelium-derived factors was assessed in isolated coronary small arteries using real-time PCR. Up 4 A (10 -9 to 10 -5 M) failed to produce contraction in isolated coronary small arteries from either Sham or AoB swine, but produced relaxation in preconstricted arteries, which was significantly blunted in AoB compared to Sham. Blockade of purinergic P1, and P2 receptors attenuated Up 4 A-induced coronary relaxation more, while the effect of P2X 1 -blockade was similar and the effects of A 2A - and P2Y 1 -blockade were reduced in AoB as compared to Sham. mRNA expression of neither A1, A2, A3, nor P2X 1 , P2X 7 , P2Y 1 , P2Y 2 , nor P2Y 6 -receptors was altered in AoB as compared to Sham, while P2Y 12 expression was higher in AoB. eNOS inhibition attenuated Up 4 A-induced coronary relaxation in both Sham and AoB. Additional blockade of cyclooxygenase enhanced Up 4 A-induced coronary relaxation in AoB but not Sham swine, suggesting the involvement

  10. Stable expression of lipocalin-type prostaglandin D synthase in cultured preadipocytes impairs adipogenesis program independently of endogenous prostanoids

    Energy Technology Data Exchange (ETDEWEB)

    Hossain, Mohammad Salim; Chowdhury, Abu Asad; Rahman, Mohammad Sharifur [Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane 690-8504 (Japan); Nishimura, Kohji [Department of Molecular and Functional Genomics, Center for Integrated Research in Science, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane 690-8504 (Japan); Jisaka, Mitsuo; Nagaya, Tsutomu [Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane 690-8504 (Japan); Shono, Fumiaki [Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Yamashiro-cho, Tokushima-shi, Tokushima 770-8514 (Japan); Yokota, Kazushige, E-mail: yokotaka@life.shimane-u.ac.jp [Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane 690-8504 (Japan)

    2012-02-15

    Lipocalin-type prostaglandin D synthase (L-PGDS) expressed preferentially in adipocytes is responsible for the synthesis of PGD{sub 2} and its non-enzymatic dehydration products, PGJ{sub 2} series, serving as pro-adipogenic factors. However, the role of L-PGDS in the regulation of adipogenesis is complex because of the occurrence of several derivatives from PGD{sub 2} and their distinct receptor subtypes as well as other functions such as a transporter of lipophilic molecules. To manipulate the expression levels of L-PGDS in cultured adipocytes, cultured preadipogenic 3T3-L1 cells were transfected stably with a mammalian expression vector having cDNA encoding murine L-PGDS oriented in the sense direction. The isolated cloned stable transfectants with L-PGDS expressed higher levels of the transcript and protein levels of L-PGDS, and synthesized PGD{sub 2} from exogenous arachidonic acid at significantly higher levels. By contrast, the synthesis of PGE{sub 2} remained unchanged, indicating no influence on the reactions of cyclooxygenase (COX) and PGE synthase. Furthermore, the ability of those transfectants to synthesize {Delta}{sup 12}-PGJ{sub 2} increased more greatly during the maturation phase. The sustained expression of L-PGDS in cultured stable transfectants hampered the storage of fats during the maturation phase of adipocytes, which was accompanied by the reduced gene expression of adipocyte-specific markers reflecting the down-regulation of the adipogenesis program. The suppressed adipogenesis was not rescued by either exogenous aspirin or peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) agonists including troglitazone and {Delta}{sup 12}-PGJ{sub 2}. Taken together, the results indicate the negative regulation of the adipogenesis program by the enhanced expression of L-PGDS through a cellular mechanism involving the interference of the PPAR{gamma} signaling pathway without the contribution of endogenous pro-adipogenic prostanoids

  11. An improved radiosynthesis of the muscarinic M2 radiopharmaceutical, [{sup 18}F]FP-TZTP

    Energy Technology Data Exchange (ETDEWEB)

    Oosten, Erik M. van [Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada); PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Wilson, Alan A.; Stephenson, Karin A. [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Mamo, David C. [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Geriatric Mental Health Program, Centre for Addiction and Mental Health, 1001 Queen Street West, Toronto, Ontario, M6J 1H4 (Canada); Pollock, Bruce G.; Mulsant, Benoit H. [Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Geriatric Mental Health Program, Centre for Addiction and Mental Health, 1001 Queen Street West, Toronto, Ontario, M6J 1H4 (Canada); Yudin, Andrei K. [Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada); Houle, Sylvain [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Vasdev, Neil [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada)], E-mail: neil.vasdev@camhpet.ca

    2009-04-15

    The radioligand 3-(4-(3-[{sup 18}F]fluoropropylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5, 6-tetrahydropyridine ([{sup 18}F]FP-TZTP) is an agonist with specificity towards subtype 2 of muscarinic acetylcholine (M2) receptors. It is currently the only radiotracer available for imaging M2 receptors in human subjects with positron emission tomography. The present study reports on an improved method for the synthesis of [{sup 18}F]FP-TZTP, automated using a GE TRACERlab{sup TM} FX{sub FN} radiosynthesis module. A key facet was the use of a new precursor, 3-(4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazol-3-ylthio) propyl 4-methylbenzenesulfonate. The precursor was fluorinated via nucleophilic displacement of the tosyloxy group by potassium cryptand [{sup 18}F]fluoride (K[{sup 18}F]/K{sub 222}) in CH{sub 3}CN at 80 deg. C for 5 min, and purified by HPLC. Formulated [{sup 18}F]FP-TZTP was prepared in an uncorrected radiochemical yield of 29{+-}4%, with a specific activity of 138{+-}41 GBq/{mu}mol (3732{+-}1109 mCi/{mu}mol) at the end of synthesis (35 min; n=3). This methodology offers higher yields, faster synthesis times, an optimized precursor, and simpler automation than previously reported.

  12. Effects of lysine clonixinate and ketorolac tromethamine on prostanoid release from various rat organs incubated ex vivo.

    Science.gov (United States)

    Pallapies, D; Salinger, A; Meyer zum Gottesberge, A; Atkins, D J; Rohleder, G; Nagyiványi, P; Peskar, B A

    1995-01-01

    The release of prostanoids from rat brain, gastric mucosa, lungs and kidneys incubated ex vivo has been investigated for up to 5 h after oral administration of 10 mg/kg lysine clonixinate or 1 mg/kg ketorolac tromethamine. Additionally, 60 min after drug administration, a time point of near-maximal inhibition of prostanoid release, the effects of 2.5, 10 and 30 mg/kg lysine clonixinate and of 0.0225, 0.15 and 1 mg/kg ketorolac tromethamine were compared. In all organs investigated both drugs inhibited fatty acid cyclooxygenase (COX) in a dose-dependent manner, but ketorolac tromethamine was more potent and had a longer-lasting effect than lysine clonixinate. While the ID50 values for lysine clonixinate were in the same order of magnitude for all 4 organs investigated, ketorolac tromethamine exhibited some organ selectivity with a particularly high activity in the kidneys. This effect might be related to the renal toxicity of ketorolac tromethamine. On the other hand, the difference in potency was smallest in brain suggesting that inhibition of central prostanoid biosynthesis could contribute to the rapid and effective inhibition of pain by both drugs. IC50 values for inhibition of purified COX-1 and COX-2 in vitro were slightly lower for lysine clonixinate (2.4 and 24.6 micrograms/ml, respectively) than for ketorolac tromethamine (3.7 and 25.6 micrograms/ml, respectively).

  13. The role of the prostaglandin D2 receptor, DP, in eosinophil trafficking

    DEFF Research Database (Denmark)

    Schratl, Petra; Royer, Julia F; Kostenis, Evi

    2007-01-01

    of DP has remained unclear. We report in this study that, in addition to CRTH2, the DP receptor plays an important role in eosinophil trafficking. First, we investigated the release of eosinophils from bone marrow using the in situ perfused guinea pig hind limb preparation. PGD2 induced the rapid......Prostaglandin (PG) D2 is a major mast cell product that acts via two receptors, the D-type prostanoid (DP) and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptors. Whereas CRTH2 mediates the chemotaxis of eosinophils, basophils, and Th2 lymphocytes, the role...

  14. [{sup 18}F]{beta}-CIT-FP is superior to [{sup 11}C]{beta}-CIT-FP for quantitation of the dopamine transporter

    Energy Technology Data Exchange (ETDEWEB)

    Lundkvist, Camilla; Halldin, Christer; Ginovart, Nathalie; Swahn, Carl-Gunnar; Farde, Lars

    1997-10-01

    {beta}-CIT-FP [N-(3-fluoropropyl)-2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)nortropane] is a cocaine analogue with high affinity for the dopamine transporter. Positron emission tomography (PET) studies with [O-methyl-{sup 11}C]{beta}-CIT-FP ([{sup 11}C]{beta}-CIT-FP) has shown that equilibrium conditions were approached but, however, not reached at the end of measurement. Moreover, metabolite studies of [{sup 11}C]{beta}-CIT-FP in monkey plasma demonstrated a lipophilic-labelled metabolite that may enter the brain. We therefore labelled {beta}-CIT-FP with fluorine-18 in a position that may avoid the formation of labelled lipophilic metabolites. The more long-lived radionuclide ({sup 18}F) was used to allow for measurements over longer time. [N-fluoropropyl-{sup 18}F]{beta}-CIT-FP ([{sup 18}F]{beta}-CIT-FP) was prepared by N-alkylation of nor-{beta}-CIT with [{sup 18}F]fluoropropyl bromide. PET studies were performed in cynomolgus monkeys. [{sup 18}F]{beta}-CIT-FP entered the brain rapidly. There was a high concentration of radioactivity in the striatum and much lower in the thalamus, neocortex, and cerebellum. The striatum-to-cerebellum ratio was about 5 at time of transient equilibrium, which occurred after 60 to 100 min. After pretreatment with GBR 12909, radioactivity in the striatum was markedly reduced, thus indicating specific [{sup 18}F]{beta}-CIT-FP binding to the dopamine transporter. The fraction of unchanged [{sup 18}F]{beta}-CIT-FP determined by HPLC was 10-15% after 140 min. No lipophilic labelled metabolites were detected. The absence of measurable lipophilic labelled metabolites and the occurrence of transient equilibrium within the time of the PET measurement indicate that [{sup 18}F]{beta}-CIT-FP is superior to [{sup 11}C]{beta}-CIT-FP as a PET radioligand for quantification of the dopamine transporter in the human brain.

  15. Present status and plans of JENDL FP data evaluation project

    International Nuclear Information System (INIS)

    Kawano, Toshihiko

    2003-01-01

    The Fission Product (FP) data evaluation is one of the key issues for the next revision of JENDL, since many data were carried over from JENDL-3.2 to 3.3. The new FP Working Group (FPWG) was organized in the Japanese Nuclear Data Committee (JNDC) to perform new evaluations of FP data for JENDL. In the present review of FP data evaluation, we show the history and current status of FP nuclear data, requirements of FP data, new measurements, the international cooperation, and the future plans toward the new JENDL. (author)

  16. Women's development key to MCH/FP.

    Science.gov (United States)

    1991-05-01

    The Sri Lankan government has included women in its development process thereby raising literacy levels to 91% for urban women and 87% for rural women. Their successful participation has in turn resulted in improvements in maternal and child health (MCH) and family planning (FP) acceptance. Indeed MCH/FP promotion could not have occurred without their participation in development. Since the 1960s, the Health and Women's Affairs Ministry continues to provide broad support for grass roots health care, such as strengthening the capacity of local clinics to increase coverage of health monitoring for women and children. There fore infant mortality in Sri Lanka has decreased from 47.5 in 1970 to 34 in 1980 to 19 in 1989. In addition, the total fertility rate fell from 5 in 1962-1964 to 3.4 in 1980-1982 to 2.8 in 1982-1987. The Ministry initiated its Integrated FP, Nutrition, and Parasite Control Project (IP) in 8 pilot areas in 1981. IP continues to encourage women's developed and MCH/FP at the grass roots level. In fact, FP acceptance rates increased from 31.8% in 1980 to 59% in 1989 in Nakulugamuwa and from 2.3% in 1980 to 70.5% in 1989 in Galnewa. The MCH component operating from community level clinics includes growth monitoring and immunization. Project activities include construction of latrines and wells, promotion of regular health examinations for mothers and children, FP education, counseling, nutrition promotion for children, and training programs for health staff, community volunteers, mothers' groups, and teachers. The volunteers form a link between the community and government health workers. Mothers' groups participate in school nutrition programs, home gardening, and income generation. Parasite control is consequently accomplished by community health and environmental sanitation promotion.

  17. Phebus FP. An international severe accident research programme

    International Nuclear Information System (INIS)

    Hardt, P.; Tattegrain, A.

    1995-01-01

    The main hazard during a hypothetical severe nuclear reactor accident resides in its fission product (FP) inventory. For this reason, the behaviour of FPs has been extensively studied, with the aim of determining the potential source to the environment. The Phebus FP programme proposes a novel, integral approach to this research. After 5 years of construction and of analytical preparation the Phebus FP programme has been supplying a large volume of new experimental data. Their processing by code calculations is presently a major challenge to all partners. The intense collaboration of 25 organizations from 15 countries has proven to be a major asset of Phebus FP. (author). 6 refs., 2 figs

  18. Nitric oxide signaling and the cross talk with prostanoids pathways in vascular system.

    Science.gov (United States)

    Silva, Bruno R; Paula, Tiago D; Paulo, Michele; Bendhack, Lusiane M

    2016-12-28

    This review provides an overview of the cellular signaling of nitric oxide (NO) and prostanoids in vascular cells and the possible cross talk between their pathways, mainly in hypertension, since the imbalance of these two systems has been attributed to development of some cardiovascular diseases. It also deals with the modulation of vasodilation induced by NO donors. NO is a well-known second messenger involved in many cellular functions. In the vascular system, the NO produced by endothelial NO-synthase (eNOS) or released by NO donors acts in vascular smooth muscle cells, the binding of NO to Fe2+-heme of soluble guanylyl-cyclase (sGC) activates sGC and the production of cyclic guanosine-3-5-monophosphate (cGMP). The second messenger (cGMP) activates protein kinase G and the signaling cascade, including K+ channels. Activation of K+ channels leads to cell membrane hyperpolarization and Ca2+ channels blockade, which induce vascular relaxation. Moreover, the enzyme cyclooxygenase (COX) is also an important regulator of the vascular function by prostanoids production such as thromboxane A2 (TXA2) and prostacyclin (PGI2), which classically induce contraction and relaxation, respectively. Additionaly, studies indicate that the activity of both enzymes can be modulated by their products and reactive oxygen species (ROS) in cardiovascular diseases such as hypertension. The interaction of NO with cellular molecules, particularly the reaction of NO with ROS, determines the biological mechanisms of action and short half-life of NO. We have been working on the vascular effects of ruthenium-derived complexes that release NO. Our research group has published works on the vasodilating effects of ruthenium-derived NO donors and the mechanisms of vascular cells involved in the relaxation of the vascular smooth muscle in health and hypertensive rats. In our previous studies, we have compared the new NO donors synthesized by our group to SNP. It shows the cellular signaling of NO

  19. Metabolism of 123I-FP-CIT in humans

    International Nuclear Information System (INIS)

    Tanaka, Akihiro; Okano, Kyoko; Tamagami, Hiroshi

    1999-01-01

    The metabolism of N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ( 123 I) ( 123 I-FP-CIT) in healthy humans was studied. Plasma and urine samples, obtained after i.v. administration of 123 I-FP-CIT, were analyzed using the two-dimensional thin-layer chromatography technique. Eleven radiochemical components were detected in both plasma and urine, and four of them were the parent 123 I-FP-CIT and its metabolites, N-(3-fluoropropyl)-2β-carboxy-3β-(4-iodophenyl)nortropane ( 123 I) ( 123 I-acid), 2β-carboxy-3β-(4-iodophenyl)nortropane ( 123 I) ( 123 I-nor-acid) and 2β-carbomethoxy-3β-(4-iodophenyl)nortropane ( 123 I) ( 123 I-nor-CIT). These four identified radiochemical components occupied about 80% or more in ratio of the radiochemical components in the plasma and urine. In the metabolites of 123 I-FP-CIT, the high polar metabolites- 123 I-acid and 123 I-nor-acid-were found to be the major components, while lipophilic 123 I-nor-CIT was a minor component. Free iodide ( 123 I - ) was not found in the plasma or urine. Thus, the main metabolic reactions which 123 I-FP-CIT undergoes in humans seem to be hydrolysis of the ester bond and N-dealkylation. In vivo deiodination of 123 I-FP-CIT was found to be minimum. Current results suggest that the metabolites of 123 I-FP-CIT hardly influence evaluation of the dopamine transporter in the human brain. (author)

  20. The retinoid X receptor response element in the human aldehyde dehydrogenase 2 promoter is antagonized by the chicken ovalbumin upstream promoter family of orphan receptors

    NARCIS (Netherlands)

    Pinaire, J; Hasanadka, R; Fang, M; Chou, WY; Stewart, MJ; Kruijer, W; Crabb, D

    2000-01-01

    Two tandem sites in the aldehyde dehydrogenase 2 promoter (designated FP330-5' and FP330-3') that bind members of the nuclear receptor superfamily mere recently identified. Antibodies against apolipoprotein regulatory protein (ARP-1) altered DNA-protein interactions in electrophoretic mobility shift

  1. Basics of FP promotion.

    Science.gov (United States)

    1994-03-01

    Joseph Van Arendonk, deputy executive director of the UN Population Fund (UNFPA), stated in an interview that UNFPA had identified the critical points of success for a family planning (FP) program. First is the public and consistent commitment of the political leadership of a country. Second, very good quality services must be readily available, the clinics should be clean, and the workers well-trained, especially in counseling. Third, services must be accessible and physically near to people, who must be informed of service availability. Fourth, women should have the ability to decide for themselves about their fertility. However, FP should be a joint decision, and therefore education for men is vital. Another important element to success is to have proper service statistics built into the FP program for assessment of the problem of dropping out and for a continuous program evaluation. Other aspects of management are good supervision and control as well as proper logistics. Although the Earth Summit made sustainable development the objective for the year 2000 and beyond, this goal is only viable if it is linked with an appropriate population policy. In population, the same kinds of challenges persist that existed 25 years ago. This is because once contraception is introduced, the relationship between men and women and the whole concept of family are changed, bringing about changes in society.

  2. The Phebus FP project

    International Nuclear Information System (INIS)

    Delchambre, P.; Von der Hardt, P.

    1989-01-01

    This report summarizes the pre-project studies concerning the PHEBUS FP facility. After recalling the programme objectives, it describes the projected modifications to the PHEBUS reactor, outlines new installations and justifies the selected options

  3. SPECT 123-I-[FP-CIT] diagnostic in the presynaptic parkinsonism

    International Nuclear Information System (INIS)

    Piperkova, E.; Georgiev, R.; Dimitrova, M.; Daskalov, M.; Orosova, M.; Milanova, M.; Danon, S.

    2005-01-01

    Detection of loss off functional dopaminergic neurone terminals in the striatum of patients with clinically uncertain Parkinsonian Syndromes will help to differentiate the Essential Tremor (ET) from the Parkinson Syndromes related to idiopathic Parkinson's Disease (PD), Multiple System Atrophy (MSA) or Progressive Supranuclear Palsy (PSP). In these cases dopaminic medication should be avoided for patients not suffering from true parkinsonism.Objective of the study is to determine the utility of [ 123 I] FP-CIT SPECT in clinically uncertain Parkinsonian syndromes and their differentiation from ET. Materials and Methods: This prospective study involved 9 patients (4 males and 5 females, aged between 38 - 81 years) with clinically uncertain Parkinsonism. The main symptoms were tremor (n=8), gait alteration (n=6), bradykinesia (n=3) and Negro phenomena positive (n=2), or a combination of these symptoms (n=9), with subsequent follow-up of 7-8 months. Dopamine agonists and antagonists acting on the postsynaptic dopamine receptors were not accepted to interfere with 123 I-Ioflupane. All patients underwent appropriate thyroid blocking by oral administration of 120 mg potassium iodide before and after [ 123 ] I FP-CIT application. All patents underwent SPECT scans 3-4 hours after i.v. injection of 185 MBq [ 123 ] FP-CIT (DaTSCAN - Amersham) on a Diacam Gamma-Camera System (Siemens). To estimate [ 123 ] FP-CIT biodistribution whole-body scans were performed, 15 minutes and 2-3 hrs after the i.v. application of the tracer. The SPECT results were evaluated visually and semi quantitatively. The [ 123 ] FP-CIT uptake of the striatum (nucleus caudatus and putamen) was referenced to the occipital cortex and to the symmetrical ROI. The scanning procedure was completed according to strict conditions for symmetry and geometry. The filtering and reconstructing procedures if the images were performed individually for each patient to avoid artifacts and errors. In all patients CT scans

  4. Precise measurements of neutron capture cross sections for FP

    International Nuclear Information System (INIS)

    Nakamura, Shoji; Harada, Hideo; Katoh, Toshio

    2000-01-01

    The thermal neutron capture cross sections (σ 0 ) and the resonance integrals (I 0 ) of some fission products (FP), such as 137 Cs, 90 Sr, 99 Tc, 129 I and 135 Cs, were measured by the activation and γ-ray spectroscopic methods. Moreover, the cross section measurements were done for other FP elements, such as 127 I, 133 Cs and 134 Cs. This paper provides the summary of the FP cross section measurements, which have been performed by authors. (author)

  5. Modeling photoabsorption of the asFP595 chromophore.

    Science.gov (United States)

    Bravaya, Ksenia B; Bochenkova, Anastasia V; Granovsky, Alexander A; Savitsky, Alexander P; Nemukhin, Alexander V

    2008-09-18

    The fluorescent protein asFP595 is a promising photoswitchable biomarker for studying processes in living cells. We present the results of a high level theoretical study of photoabsorption properties of the model asFP595 chromophore molecule in biologically relevant protonation states: anionic, zwitterionic, and neutral. Ground state equilibrium geometry parameters are optimized in the PBE0/(aug)-cc-pVDZ density functional theory approximation. An augmented version of multiconfigurational quasidegenerate perturbation theory (aug-MCQDPT2) following the state-averaged CASSCF/(aug)-cc-pVDZ calculations is used to estimate the vertical S0-S1 excitation energies for all chromophore species. An accuracy of this approach is validated by comparing the computed estimates of the S0-S1 absorption maximum of the closely related chromophore from the DsRed protein to the known experimental value in the gas phase. An influence of the CASSCF active space on the aug-MCQDPT2 excitation energies is analyzed. The zwitterionic form of the asFP595 chromophore is found to be the most sensitive to a particular choice and amount of active orbitals. This observation is explained by the charge-transfer type of the S0-S1 transition involving the entire conjugated pi-electron system for the zwitterionic protonation state. According to the calculation results, the anionic form in the trans conformation is found to possess the most red-shifted absorption band with the maximum located at 543 nm. The bands of the zwitterionic and neutral forms are considerably blue-shifted compared to those of the anionic form. These conclusions are at variance with the results obtained in the TDDFT approximation for the asFP595 chromophore. The absorption wavelengths computed in the aug-MCQDPT2/CASSCF theory are as follows: 543 (535), 470 (476), and 415 (417) nm for the anionic, zwitterionic, and neutral forms of the trans and cis (in parentheses) isomers of the asFP595 chromophore. These data can be used as a

  6. Results and exploitation of FP-4 and FP-5 research in the area 'Safety of existing installations'. Part II

    International Nuclear Information System (INIS)

    Goethem, G. van; Zurita, A.; Manolatos, P.; Casalta, S.

    2004-01-01

    An overview is given of the most important achievements of the research programme co-financed by the European Union (EU) in the area of LWR safety over the FP-4 and FP-5 periods from the end-users point of view. The end-users are: the contracting organisations (i.e. utilities and associated engineering companies, regulatory bodies and associated technical safety organisations, manufacturing industry and associated services), the non-contracting organisations (including decision makers and opinion leaders) and the European Commission. Besides Community research strategy and programme implementation aspects in general, this paper is focusing on the S/T achievements obtained by multi-partner projects in the - 7 clusters of multi-partner projects in Euratom FP-4 (1994-1998): AGE for structural ageing, INV and EXV for in-vessel core degradation and ex-vessel molten corium coolability, ST for radiological source term, CONT for containment integrity, AMM for accident management measures and INNO for innovative safety features - the total cost of the 67 multipartner projects comprised in this Community research was Euro 71.3 million, out of which Euro 35.9 million was contributed by the EU budget - 3 clusters of multi-partner projects in Euratom FP-5 (1998-2002): PLEM for plant life extension and management; SAM for severe accident management and EVOL for evolutionary safety concepts - the total cost of the 71 multipartner projects comprised in this Community research is Euro 85.4 million, out of which Euro 43.5 million is contributed by the EU budget. The objectives of this Community research are discussed and a number of FP-4 and FP-5 projects are selected to demonstrate to what extent the proposed objectives were indeed met. Besides technological requirements, socio-economic aspects are becoming increasingly important due to the level of public and political acceptance and to the economic pressure of deregulated electricity markets; this is also discussed. Finally the

  7. Simulation of COMEDIE Fission Product Plateout Experiment Using GAMMA-FP

    International Nuclear Information System (INIS)

    Tak, Nam-il; Yoon, Churl

    2014-01-01

    FThis phenomenon is particularly important under a VHTR design with vented low pressure confinement (VLPC), because the vent allows the prompt release of fission products accumulated within the primary circuit to environment during an initial blow-down phase after pipe break accidents. In order to analyze the fission product plateout, an numerical model was developed by Yoo et al. and incorporated into the GAMMA-FP code in the past. The GAMMA-FP model was validated against two experiment data, i.e., VAMPYR-1 and OGL, during the development phase. One of the well-known experiments for fission product plateout is the COMEDIE experiment. In this work, the COMEDIE experiment has been simulated using the GAMMA-FP code to investigate the reliability and applicability of the plateout model of GAMMA-FP. The COMEDIE experiment for fission product plateout was simulated using the GAMMA-FP code in this work. A good agreement was achieved between the measured and predicted plateout activities. The existing solution scheme was modified to allow larger time step size for fission product analysis in order to speed-up the computational time. Nevertheless, the modification of the existing numerical model of GAMMA-FP is necessary when a simulation capability of a long duration of plateout period (e.g., 60 years) is targeted

  8. Mechanisms underlying sodium nitroprusside-induced tolerance in the mouse aorta: Role of ROS and cyclooxygenase-derived prostanoids.

    Science.gov (United States)

    Diniz, Mariana C; Olivon, Vania C; Tavares, Lívia D; Simplicio, Janaina A; Gonzaga, Natália A; de Souza, Daniele G; Bendhack, Lusiane M; Tirapelli, Carlos R; Bonaventura, Daniella

    2017-05-01

    To determine the role of reactive oxygen species (ROS) on sodium nitroprusside (SNP)-induced tolerance. Additionally, we evaluated the role of ROS on NF-κB activation and pro-inflammatory cytokines production during SNP-induced tolerance. To induce in vitro tolerance, endothelium-intact or -denuded aortic rings isolated from male Balb-c mice were incubated for 15, 30, 45 or 60min with SNP (10nmol/L). Tolerance to SNP was observed after incubation of endothelium-denuded, but not endothelium-intact aortas for 60min with this inorganic nitrate. Pre-incubation of denuded rings with tiron (superoxide anion (O 2 - ) scavenger), and the NADPH oxidase inhibitors apocynin and atorvastatin reversed SNP-induced tolerance. l-NAME (non-selective NOS inhibitor) and l-arginine (NOS substrate) also prevented SNP-induced tolerance. Similarly, ibuprofen (non-selective cyclooxygenase (COX) inhibitor), nimesulide (selective COX-2 inhibitor), AH6809 (prostaglandin PGF 2 α receptor antagonist) or SQ29584 [PGH 2 /thromboxane TXA 2 receptor antagonist] reversed SNP-induced tolerance. Increased ROS generation was detected in tolerant arteries and both tiron and atorvastatin reversed this response. Tiron prevented tolerance-induced increase on O 2 - and hydrogen peroxide (H 2 O 2 ) levels. The increase onp65/NF-κB expression and TNF-α production in tolerant arteries was prevented by tiron. The major new finding of our study is that SNP-induced tolerance is mediated by NADPH-oxidase derived ROS and vasoconstrictor prostanoids derived from COX-2, which are capable of reducing the vasorelaxation induced by SNP. Additionally, we found that ROS mediate the activation of NF-κB and the production of TNF-α in tolerant arteries. These findings identify putative molecular mechanisms whereby SNP induces tolerance in the vasculature. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. The Phebus FP thermal-hydraulic analysis with Melcor

    Energy Technology Data Exchange (ETDEWEB)

    Akgane, Kikuo; Kiso, Yoshihiro [Nuclear Power Engineering Corporation, Tokyo (Japan); Fukahori, Takanori [Hitachi Engineering Company, Ltd., Hitachi-shi Ibaraki-ken (Japan); Yoshino, Mamoru [Nuclear Engineering Ltd., Tosabori Nishi-ku (Japan)

    1995-09-01

    The severe accident analysis code MELCOR, version 1.8.2, has been applied for thermal-hydraulic pre-test analysis of the first test of the Phebus FP program (test FPT-0) to study the best test parameters and the applicability of the code. The Phebus FP program is an in-pile test program which has been planned by the French Commissariate a L`Energie Atomique and the Commission of the European Union. The experiments are being conducted by an international collaboration to study the release and transport of fission products (FPs) under conditions assumed to be the most representative of those that would occur in a severe accident. The Phebus FP test apparatus simulates a test bundle of an in-pile section, the circuit including the steam generator U-tubes and the containment. The FPT-0 test was designed to simulate the heat-up and subsequent fuel bundle degradation after a loss of coolant severe accident, using fresh fuel. Two options for fuel degradation models in MELCOR have been applied to fuel degradation behavior. the first model assumes that fuel debris will be formed immediately after the fuel support fails by cladding relocation due to the candling process. The other is the uncollapsed bare fuel pellets option, in which the fuel pellets remain standing in a columnar shape until the fuel reaches its melting point, even if the cladding has been relocated by candling. The thermal-hydraulic behaviors in the circuit and containment of Phebus FP are discussed herein. Flow velocities in the Phebus FP circuit are high in order to produce turbulent flow in a small diameter test pipe. The MELCOR calculation has shown that the length of the hot leg and steam generator are adequate to attain steam temperatures or 700{degrees}C and 150{degrees}C in the respective outlets. The containment atmosphere temperature and humidity derived by once through integral system calculation show that objective test conditions would be satisfied in the Phebus FP experiment.

  10. The Phebus FP thermal-hydraulic analysis with Melcor

    International Nuclear Information System (INIS)

    Akgane, Kikuo; Kiso, Yoshihiro; Fukahori, Takanori; Yoshino, Mamoru

    1995-01-01

    The severe accident analysis code MELCOR, version 1.8.2, has been applied for thermal-hydraulic pre-test analysis of the first test of the Phebus FP program (test FPT-0) to study the best test parameters and the applicability of the code. The Phebus FP program is an in-pile test program which has been planned by the French Commissariate a L'Energie Atomique and the Commission of the European Union. The experiments are being conducted by an international collaboration to study the release and transport of fission products (FPs) under conditions assumed to be the most representative of those that would occur in a severe accident. The Phebus FP test apparatus simulates a test bundle of an in-pile section, the circuit including the steam generator U-tubes and the containment. The FPT-0 test was designed to simulate the heat-up and subsequent fuel bundle degradation after a loss of coolant severe accident, using fresh fuel. Two options for fuel degradation models in MELCOR have been applied to fuel degradation behavior. the first model assumes that fuel debris will be formed immediately after the fuel support fails by cladding relocation due to the candling process. The other is the uncollapsed bare fuel pellets option, in which the fuel pellets remain standing in a columnar shape until the fuel reaches its melting point, even if the cladding has been relocated by candling. The thermal-hydraulic behaviors in the circuit and containment of Phebus FP are discussed herein. Flow velocities in the Phebus FP circuit are high in order to produce turbulent flow in a small diameter test pipe. The MELCOR calculation has shown that the length of the hot leg and steam generator are adequate to attain steam temperatures or 700 degrees C and 150 degrees C in the respective outlets. The containment atmosphere temperature and humidity derived by once through integral system calculation show that objective test conditions would be satisfied in the Phebus FP experiment

  11. FP-4 and FP-5 Euratom research activities in the field of plant life management

    International Nuclear Information System (INIS)

    Lemaitre, P.; Goethem, G. van

    2001-01-01

    In this paper an overview is given of the European Union (EU) Euratom research conducted through shared cost and concerted actions in the field of plant life management. After a general introduction on the organisation of the research framework programmes the achievements of the 4th framework programme (FP-4/1994-1998) and the activities under the 5th framework programme (FP-5/1999-2002) in the field of plant life management are presented and discussed in detail. Besides technological safety requirements, socio-economic aspects are becoming increasingly important due to the level of public and political acceptance and to the economic pressure of deregulated electricity markets. It is shown that research conducted in the Euratom framework may contribute to meet these requirements, thereby maintaining nuclear power as a competitive and sustainable option for the energy policy of the European Union. (author)

  12. Biotechnological Fluorescent Ligands of the Bradykinin B1 Receptor: Protein Ligands for a Peptide Receptor.

    Directory of Open Access Journals (Sweden)

    Xavier Charest-Morin

    Full Text Available The bradykinin (BK B1 receptor (B1R is a peculiar G protein coupled receptor that is strongly regulated to the point of being inducible in immunopathology. Limited clinical evidence suggests that its expression in peripheral blood mononuclear cells is a biomarker of active inflammatory states. In an effort to develop a novel imaging/diagnostic tool, we report the rational design and testing of a fusion protein that is a ligand of the human B1R but not likely to label peptidases. This ligand is composed of a fluorescent protein (FP (enhanced green FP [EGFP] or mCherry prolonged at its N-terminus by a spacer peptide and a classical peptide agonist or antagonist (des-Arg9-BK, [Leu8]des-Arg9-BK, respectively. The design of the spacer-ligand joint peptide was validated by a competition assay for [3H]Lys-des-Arg9-BK binding to the human B1R applied to 4 synthetic peptides of 18 or 19 residues. The labeling of B1R-expressing cells with EGFP or mCherry fused with 7 of such peptides was performed in parallel (microscopy. Both assays indicated that the best design was FP-(Asn-Glyn-Lys-des-Arg9-BK; n = 15 was superior to n = 5, suggesting benefits from minimizing steric hindrance between the FP and the receptor. Cell labeling concerned mostly plasma membranes and was inhibited by a B1R antagonist. EGFP-(Asn-Gly15-Lys-des-Arg9-BK competed for the binding of [3H]Lys-des-Arg9-BK to human recombinant B1R, being only 10-fold less potent than the unlabeled form of Lys-des-Arg9-BK to do so. The fusion protein did not label HEK 293a cells expressing recombinant human BK B2 receptors or angiotensin converting enzyme. This study identifies a modular C-terminal sequence that can be adapted to protein cargoes, conferring high affinity for the BK B1R, with possible applications in diagnostic cytofluorometry, histology and drug delivery (e.g., in oncology.

  13. The PHEBUS FP project. Status report 1989-1990

    International Nuclear Information System (INIS)

    Scott de Martinville, E.F.; Delchambre, P.; Von der Hardt, P.

    1992-01-01

    Major achievements of PHEBUS Fission Product (FP) Programme during the year 1989 have been - seismic safety studies and civil engineering design of buildings and major components - transition into the detail design phase of experimental equipment and instrumentation - first orders for large components and other long delivery items - detailed definition of the test matrix - adaptation of existing, and generation of specific computation tools - dimensioning verification of the overall design proposal and of the first irradiation test - specific supporting studies, like analytical aerosol experiments, FP chemistry research, gamma spectrometry system layout, neutronic calculations. This report describes the experimental equipment, as defined in spring of 1990, and the underlying analytical studies. It updates earlier publications but can be read as a stand-alone description of PHEBUS FP. The present schedule forecasts the first in-pile test, with fresh fuel, by the middle of 1992

  14. osFP: a web server for predicting the oligomeric states of fluorescent proteins.

    Science.gov (United States)

    Simeon, Saw; Shoombuatong, Watshara; Anuwongcharoen, Nuttapat; Preeyanon, Likit; Prachayasittikul, Virapong; Wikberg, Jarl E S; Nantasenamat, Chanin

    2016-01-01

    Currently, monomeric fluorescent proteins (FP) are ideal markers for protein tagging. The prediction of oligomeric states is helpful for enhancing live biomedical imaging. Computational prediction of FP oligomeric states can accelerate the effort of protein engineering efforts of creating monomeric FPs. To the best of our knowledge, this study represents the first computational model for predicting and analyzing FP oligomerization directly from the amino acid sequence. After data curation, an exhaustive data set consisting of 397 non-redundant FP oligomeric states was compiled from the literature. Results from benchmarking of the protein descriptors revealed that the model built with amino acid composition descriptors was the top performing model with accuracy, sensitivity and specificity in excess of 80% and MCC greater than 0.6 for all three data subsets (e.g. training, tenfold cross-validation and external sets). The model provided insights on the important residues governing the oligomerization of FP. To maximize the benefit of the generated predictive model, it was implemented as a web server under the R programming environment. osFP affords a user-friendly interface that can be used to predict the oligomeric state of FP using the protein sequence. The advantage of osFP is that it is platform-independent meaning that it can be accessed via a web browser on any operating system and device. osFP is freely accessible at http://codes.bio/osfp/ while the source code and data set is provided on GitHub at https://github.com/chaninn/osFP/.Graphical Abstract.

  15. FP plate-out and compound formation analysis in hot helium coolant of 600 MWt GTHTR300 system by FP concentration difference diffusion and aerosol-condensation mechanism

    International Nuclear Information System (INIS)

    Ishiyama, Shintaro

    2004-01-01

    To estimate FP deposition rate on the typical turbomachinary, including gas turbine of GTHTR300 and exposure dose limit at its maintenance, FP plate-out analysis was been carried out using FP compound formation theory and FP concentration controlled diffusion mechanism. As the results, following conclusions were derived; (1) It is found that the analysis data computed by the VICTORIA code with assumption of the correct thickness of reactive zone exhibits very good correlation with the experimental data obtained by simulated FP plate-out experiment. (2) 137 Cs, 110m Ag and 137 Cs (131+133) I compound are major fission products deposited on the surface of turbomachinery. (3) Deposition rates of major FPs on the surface of gas turbine blade and disk are (131+133) I> 137 Cs> 110m Ag. (4) Total dose rate and allowable work time at turbine of GTHTR300 are given as 19.2 mSv/h and 2.6 h by VICTORIA code analysis and these values are conservative than that given by simple code analysis. (author)

  16. Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors

    OpenAIRE

    Tunaru, Sorin; Althoff, Till F.; Nüsing, Rolf M.; Diener, Martin; Offermanns, Stefan

    2012-01-01

    Castor oil is one of the oldest drugs. When given orally, it has a laxative effect and induces labor in pregnant females. The effects of castor oil are mediated by ricinoleic acid, a hydroxylated fatty acid released from castor oil by intestinal lipases. Despite the wide-spread use of castor oil in conventional and folk medicine, the molecular mechanism by which ricinoleic acid acts remains unknown. Here we show that the EP3 prostanoid receptor is specifically activated by ricinoleic acid and...

  17. Whither α-FP in the diagnosis of hepatocellular carcinoma?

    Directory of Open Access Journals (Sweden)

    Kew MC

    2015-08-01

    Full Text Available Michael C Kew1,2 1Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, 2University of the Witwatersrand, Johannesburg, South Africaα-FP is an α1-globulin present in high concentration in the fetal serum of mammals. It is the dominant plasma protein in the developing embryo, and is synthesized by the embryonal liver, by the endodermal cells of the visceral yolk sac, and, in very small amounts, by the embryonal intestine.1 Approximately 80% of fetal hepatocytes synthesize and secrete α-FP. The protein has been closely conserved throughout phylogenesis, suggesting that it has functions essential to the fetus, although precisely what these functions are remains to be learned. There does, however, appear to be an inverse relationship between serum α-FP and albumin levels, suggesting that α-FP might function as fetal albumin.2 Other possible biological properties of the α1-globulin include binding to estrogens and bilirubin, immunosuppressive activity, and a growth-promoting potential.3 The serum level of the protein remains constant until week 32, when it begins to sharply decrease. After birth, production of α-FP normally remains completely repressed, and serum concentrations are correspondingly very low.

  18. Modulus, Strength and Thermal Exposure Studies of FP-Al2O3/Aluminum and FP-Al2O3/Magnesium Composites.

    Science.gov (United States)

    1981-01-01

    for the ~AUG18IS~ 1W Symposium on Comites and Advanced Materials*M sponsored by the American Ceramic Society Coco Beach, Florida, January 18424, 1981E...properties of cFP-A203 fiber reinforced composites prepared by liquid metal infiltration f a techniques. The first approach was the incorporation of a...coated FP-A1203 fibers in the composites. This coating is readily wet by molten aluminum and permitted the use of more conventional aluminum alloys

  19. Curcumin improves prostanoid ratio in diabetic mesenteric arteries associated with cyclooxygenase-2 and NF-κB suppression

    Directory of Open Access Journals (Sweden)

    Patumraj S

    2010-12-01

    Full Text Available Sirada Rungseesantivanon1, Naris Thengchaisri4, Preecha Ruangvejvorachai2, Suthiluk Patumraj31Interdepartment of Physiology, Graduate School, 2Department of Pathology, 3Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 4Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, ThailandBackground: Curcumin, the active ingredient from turmeric rhizomes, has been shown to have a wide range of pharmacological properties including antioxidant and anti-inflammatory effects. Curcumin has been reviewed for its multiple molecular action on inhibiting tumor angiogenesis via its mechanisms of cyclooxygenase (COX-2, and vascular endothelial growth factor (VEGF inhibition. In this present study, we aimed to assess the effects of curcumin on preventing diabetes-induced vascular dysfunction in association with COX-2, nuclear factor-κB (NF-κB expression, and prostanoid production.Methods: Twelve-week-old male Wistar rats were separated into five groups: 1 diabetes with 0.9% normal saline (DM-NSS; n = 10, 2 diabetes treated with curcumin 30 mg/kg (n = 10, 3 diabetes treated with curcumin 300 mg/kg (n = 10, 4 the control with 0.9% normal saline (n = 10, and 5 the control treated with 300 mg/kg (n = 10. Daily oral feeding of curcumin was started at 6 weeks after the streptozotocin injection. Levels of 6-keto prostaglandin (PG F1α and thromboxane (TX B2 were determined from mesenteric perfusates using enzyme immunoassay kits. Protein kinase C (PKC-ßII and COX-2 with NF-κB levels were analyzed in the mesenteric arteries by immunofluorescent staining and immunohistochemistry, respectively.Results: The ratio of 6-keto-PGF1α and TXB2 was significantly decreased in DM-NSS compared with the control (P < 0.05. Double-immunofluorescent staining with specific antibodies for PKC-βII and a-smooth muscle actins showed that the diabetic mesenteric arteries contained increased

  20. PHEBUS FP release analysis using a microstructure-based code

    International Nuclear Information System (INIS)

    Carlucci, L.N.

    1992-03-01

    The results of pre-test fission-product (FP) release analyses of the first two PHEBUS FP experiments, FPT0 and FPT1, indicate that the FREEDOM microstructure-based code predicts significant differences in both the timing and percent of gaseous FP releases for the two tests. To provide an indication of its predictive capability, FREEDOM was also used to model the high-burnup fuel tested in the Oak Ridge National Laboratory experiments VI-2 and VI-3. For these, the code was found to overpredict releases during the early stages of the tests and to underpredict releases during the later stages. The release kinetics in both tests were reasonably predicted, however. In view of the above, it is likely that the FREEDOM predictions of the final cumulative releases for the first two PHEBUS FP tests are lower-bound estimates. However, the significant difference in the predicted timing of initial releases for the two tests is felt to be indicative of what will occur. Therefore, this difference should be considered in the planning and conduct of the two tests, particularly aspects related to on-line measurements

  1. Functional-light JavaScript balanced, pragmatic FP in JavaScript

    CERN Document Server

    Simpson, Kyle

    2017-01-01

    Functional-Light JavaScript is a balanced, pragmatic exploration of Functional Programming in JavaScript. Functional Programming (FP) is an incredibly powerful paradigm for structuring code that yields more robust, verifiable, and readable programs. If you've ever tried to learn FP but struggled with terms like "monad", mathematical concepts like category theory, or symbols like (lambda), you're not alone. Functional-Light programming distills the most vital aspects of FP—function purity, value immutability, composition, and more!—down to approachable JavaScript patterns. Rather than the all-or-nothing dogmatism often encountered in FP, this book teaches you how to improve your programs line by line.

  2. Computer Security: Well fought, FP!

    CERN Multimedia

    Stefan Lueders, Computer Security Team

    2015-01-01

    We are used to spam and phishing emails. But at the end of last year, a very special email struck one of our colleagues in the FP Department.   An accountant was gently asked in an email from “Rolf.Heuer@cern.ch” to prepare a financial transaction - in the strictest confidence. A phone call from the beneficiary to the accountant was made in an attempt to support this request. Despite being instructed not to talk to anyone, the e-mail, the phone conversation and the circumstances were all so suspicious that our colleague consulted his hierarchy, the internal audit service and us. Well done, FP Department! This is a rare case of an attempt at “social engineering”, i.e. luring someone into doing something detrimental to the Organization. The e-mail was fake. While it appeared to come from “Rolf.Heuer@cern.ch”, it actually came from an alleged fraudster outside CERN. The e-mail and the phone call showed that he was well prepared and dire...

  3. CERN in FP7: very successful participation so far

    CERN Multimedia

    2009-01-01

    The first two years of the seventh Framework Programme were very successful for CERN – 27 EU projects were selected for funding in 2007 and 2008, with the total EC contribution exceeding 33 million euros.The seventh European Union Framework Programme for research, technological development and demonstration activities (FP7) started on 1 January 2007 and will cover the period from 2007 to 2013. With a total budget of 50.5 billion euros, FP7 is the largest Framework Programme in the history of the EU. FP7 consists of four major sub-programmes, referred to as "Specific Programmes": "Cooperation" is focused on collaborative research projects and is divided into 10 thematic areas. "Ideas" is a new EU programme for funding frontier research in all fields of science. "Capacities" aims at strengthening the research capacities in Europe, including research infrastructures and e-infrastructures. Finally, "People" succeeds the p...

  4. Study of fp States in Nuclei with High Neutron Excess

    CERN Multimedia

    2002-01-01

    Previous results obtained at ISOLDE on GT transitions in n-rich Na and Mg nuclei have shown the sharp decrease of excitation energy for fp states when A$>$29. \\\\ \\\\ Independently, shell model calculations have revealed that the onset of a deformation region near N=20 for Ne, Na and Mg nuclei was related to a sudden transition in the ground state properties with the appearance of a major (sd)$^{-2}$(fp)$^2$ component. \\\\ \\\\ We propose to use the new possibilities of producing and detecting n-rich nuclei to study by $\\gamma$ and n spectroscopy the properties of fp states with different cores: around N=20 (Na, Mg and Al) and N=28 (Ar, K and Ca). In particular, the cases of $^3

  5. DASH-FP, Multicomponent Time-Dependent Concentration Diffusion

    International Nuclear Information System (INIS)

    Apperson, C.E. Jr.; Carruthers, L.M.; Shinn, J.F.; Lee, C.E.

    1995-01-01

    1 - Description of program or function: The program DASH-FP calculates the transient concentration of multiple diffusing species with radioactive decay. 2 - Method of solution: Uses finite difference and exponential operator techniques

  6. Influence of Prostanoids in the Diuretic and Natriuretic Effects of Extracts and Kaempferitrin from Bauhinia forficata Link Leaves in Rats.

    Science.gov (United States)

    de Souza, Priscila; da Silva, Luisa Mota; Boeing, Thaise; Somensi, Lincon Bordignon; Cechinel-Zanchett, Camile Cecconi; Campos, Adriana; Krueger, Clarissa de Medeiros Amorim; Bastos, Jairo Kenupp; Cechinel-Filho, Valdir; Andrade, Sérgio Faloni de

    2017-10-01

    Although Bauhinia forficata Link is popularly used in Brazil to induce diuresis, no scientific investigation has focused on demonstrating its efficacy in preclinical trials. For that, normotensive male Wistar and spontaneously hypertensive rats were used to test the effect of extracts and kaempferitrin obtained from Bauhinia forficata leaves in the experimental model of diuresis. Cumulative urine volume, Na + and K + excretion, calcium, creatinine, prostaglandin E 2 , pH, density, and conductivity were measured at the end of the experiment (after 8 or 24 h). The treatment with aqueous infusion, methanolic extract, trichloromethane, or ethyl acetate-butanolic fractions significantly increase urinary volume and electrolytes levels when orally given to rats, without altering the pH or density parameters. Kaempferitrin induced diuretic, natriuretic, but not kaliuretic effects in both normotensive and hypertensive rats. In addition, kaempferitrin enhanced urinary creatinine and prostaglandin E 2 excretion, without modifying calcium levels. Kaempferitrin-induced diuresis was unaffected by previous treatment with a nonselective inhibitor of nitric oxide synthase and neither with a nonselective muscarinic receptor antagonist. On the other hand, a cyclooxygenase inhibitor was able to decrease its effect when compared with vehicle-treated rats, suggesting that the diuretic and natriuretic properties from kaempferitrin are associated with endogenous prostanoids generation. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Genetics, structure, and prevalence of FP967 (CDC Triffid) T-DNA in flax.

    Science.gov (United States)

    Young, Lester; Hammerlindl, Joseph; Babic, Vivijan; McLeod, Jamille; Sharpe, Andrew; Matsalla, Chad; Bekkaoui, Faouzi; Marquess, Leigh; Booker, Helen M

    2015-01-01

    The detection of T-DNA from a genetically modified flaxseed line (FP967, formally CDC Triffid) in a shipment of Canadian flaxseed exported to Europe resulted in a large decrease in the amount of flax planted in Canada. The Canadian flaxseed industry undertook major changes to ensure the removal of FP967 from the supply chain. This study aimed to resolve the genetics and structure of the FP967 transfer DNA (T-DNA). The FP967 T-DNA is thought to be inserted in at single genomic locus. The junction between the T-DNA and genomic DNA consisted of two inverted Right Borders with no Left Border (LB) flanking genomic DNA sequences recovered. This information was used to develop an event-specific quantitative PCR (qPCR) assay. This assay and an existing assay specific to the T-DNA construct were used to determine the genetics and prevalence of the FP967 T-DNA. These data supported the hypothesis that the T-DNA is present at a single location in the genome. The FP967 T-DNA is present at a low level (between 0.01 and 0.1%) in breeder seed lots from 2009 and 2010. None of the 11,000 and 16,000 lines selected for advancement through the Flax Breeding Program in 2010 and 2011, respectively, tested positive for the FP967 T-DNA, however. Most of the FP967 T-DNA sequence was resolved via PCR cloning and next generation sequencing. A 3,720 bp duplication of an internal portion of the T-DNA (including a Right Border) was discovered between the flanking genomic DNA and the LB. An event-specific assay, SAT2-LB, was developed for the junction between this repeat and the LB.

  8. PanFP: pangenome-based functional profiles for microbial communities.

    Science.gov (United States)

    Jun, Se-Ran; Robeson, Michael S; Hauser, Loren J; Schadt, Christopher W; Gorin, Andrey A

    2015-09-26

    For decades there has been increasing interest in understanding the relationships between microbial communities and ecosystem functions. Current DNA sequencing technologies allows for the exploration of microbial communities in two principle ways: targeted rRNA gene surveys and shotgun metagenomics. For large study designs, it is often still prohibitively expensive to sequence metagenomes at both the breadth and depth necessary to statistically capture the true functional diversity of a community. Although rRNA gene surveys provide no direct evidence of function, they do provide a reasonable estimation of microbial diversity, while being a very cost-effective way to screen samples of interest for later shotgun metagenomic analyses. However, there is a great deal of 16S rRNA gene survey data currently available from diverse environments, and thus a need for tools to infer functional composition of environmental samples based on 16S rRNA gene survey data. We present a computational method called pangenome-based functional profiles (PanFP), which infers functional profiles of microbial communities from 16S rRNA gene survey data for Bacteria and Archaea. PanFP is based on pangenome reconstruction of a 16S rRNA gene operational taxonomic unit (OTU) from known genes and genomes pooled from the OTU's taxonomic lineage. From this lineage, we derive an OTU functional profile by weighting a pangenome's functional profile with the OTUs abundance observed in a given sample. We validated our method by comparing PanFP to the functional profiles obtained from the direct shotgun metagenomic measurement of 65 diverse communities via Spearman correlation coefficients. These correlations improved with increasing sequencing depth, within the range of 0.8-0.9 for the most deeply sequenced Human Microbiome Project mock community samples. PanFP is very similar in performance to another recently released tool, PICRUSt, for almost all of survey data analysed here. But, our method is unique

  9. Global scaling for semi-quantitative analysis in FP-CIT SPECT.

    Science.gov (United States)

    Kupitz, D; Apostolova, I; Lange, C; Ulrich, G; Amthauer, H; Brenner, W; Buchert, R

    2014-01-01

    Semi-quantitative characterization of dopamine transporter availability from single photon emission computed tomography (SPECT) with 123I-ioflupane (FP-CIT) is based on uptake ratios relative to a reference region. The aim of this study was to evaluate the whole brain as reference region for semi-quantitative analysis of FP-CIT SPECT. The rationale was that this might reduce statistical noise associated with the estimation of non-displaceable FP-CIT uptake. 150 FP-CIT SPECTs were categorized as neurodegenerative or non-neurodegenerative by an expert. Semi-quantitative analysis of specific binding ratios (SBR) was performed with a custom-made tool based on the Statistical Parametric Mapping software package using predefined regions of interest (ROIs) in the anatomical space of the Montreal Neurological Institute. The following reference regions were compared: predefined ROIs for frontal and occipital lobe and whole brain (without striata, thalamus and brainstem). Tracer uptake in the reference region was characterized by the mean, median or 75th percentile of its voxel intensities. The area (AUC) under the receiver operating characteristic curve was used as performance measure. The highest AUC of 0.973 was achieved by the SBR of the putamen with the 75th percentile in the whole brain as reference. The lowest AUC for the putamen SBR of 0.937 was obtained with the mean in the frontal lobe as reference. We recommend the 75th percentile in the whole brain as reference for semi-quantitative analysis in FP-CIT SPECT. This combination provided the best agreement of the semi-quantitative analysis with visual evaluation of the SPECT images by an expert and, therefore, is appropriate to support less experienced physicians.

  10. Role of nitric oxide and prostanoids in the regulation of leg blood flow and blood pressure in humans with essential hypertension: effect of high-intensity aerobic training

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Jensen, Lasse Gliemann; Thaning, Pia

    2012-01-01

    We examined the role of nitric oxide (NO) and prostanoids in the regulation of leg blood flow and systemic blood pressure before and after 8 weeks of aerobic high-intensity training in individuals with essential hypertension (n=10) and matched healthy control subjects (n=11). Hypertensive subjects...

  11. Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes.

    Science.gov (United States)

    Santhosh, K T; Elkhateeb, O; Nolette, N; Outbih, O; Halayko, A J; Dakshinamurti, S

    2011-07-01

    Neonatal pulmonary hypertension (PPHN) is characterized by pulmonary vasoconstriction, due in part to dysregulation of the thromboxane prostanoid (TP) receptor. Hypoxia induces TP receptor-mediated hyperresponsiveness, whereas serine phosphorylation mediates desensitization of TP receptors. We hypothesized that prostacyclin (IP) receptor activity induces TP receptor phosphorylation and decreases ligand affinity; that TP receptor sensitization in hypoxic myocytes is due to IP receptor inactivation; and that this would be reversible by the cAMP-specific phosphodiesterase inhibitor milrinone. We examined functional regulation of TP receptors by serine phosphorylation and effects of IP receptor stimulation and protein kinase A (PKA) activity on TP receptor sensitivity in myocytes from neonatal porcine resistance pulmonary arteries after 72 h hypoxia in vitro. Ca(2+) response curves to U46619 (TP receptor agonist) were determined in hypoxic and normoxic myocytes incubated with or without iloprost (IP receptor agonist), forskolin (adenylyl cyclase activator), H8 (PKA inhibitor) or milrinone. TP and IP receptor saturation binding kinetics were measured in presence of iloprost or 8-bromo-cAMP. Ligand affinity for TP receptors was normalized in vitro by IP receptor signalling intermediates. However, IP receptor affinity was compromised in hypoxic myocytes, decreasing cAMP production. Milrinone normalized TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptor phosphorylation. TP receptor sensitivity and EC(50) for TP receptor agonists was regulated by PKA, as TP receptor serine phosphorylation by PKA down-regulated Ca(2+) mobilization. Hypoxia decreased IP receptor activity and cAMP generation, inducing TP receptor hyperresponsiveness, which was reversed by milrinone. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  12. JNDC FP decay data file

    International Nuclear Information System (INIS)

    Yamamoto, Tohru; Akiyama, Masatsugu

    1981-02-01

    The decay data file for fission product nuclides (FP DECAY DATA FILE) has been prepared for summation calculation of the decay heat of fission products. The average energies released in β- and γ-transitions have been calculated with computer code PROFP. The calculated results and necessary information have been arranged in tabular form together with the estimated results for 470 nuclides of which decay data are not available experimentally. (author)

  13. [123I]FP-CIT binding in rat brain after acute and sub-chronic administration of dopaminergic medication

    International Nuclear Information System (INIS)

    Lavalaye, J.; Knol, R.J.J.; Bruin, K. de; Reneman, L.; Booij, J.; Janssen, A.G.M.

    2000-01-01

    The recently developed radioligand [ 123 I]FP-CIT is suitable for clinical single-photon emission tomography (SPET) imaging of the dopamine (DA) transporter in vivo. To date it has remained unclear whether dopaminergic medication influences the striatal [ 123 I]FP-CIT binding. The purpose of this study was to investigate the influence of this medication on [ 123 I]FP-CIT binding in the brain. We used an animal model in which we administered dopaminomimetics, antipsychotics and an antidepressant. In vivo [ 123 I]FP-CIT binding to the DA and serotonin transporters was evaluated after sub-chronic and acute administration of the drugs. The administered medication induced small changes in striatal [ 123 I]FP-CIT binding which were not statistically significant. As expected, the DA reuptake blocker GBR 12,909 induced a significant decrease in [ 123 I]FP-CIT binding. [ 123 I]FP-CIT binding in the serotonin-rich hypothalamus was decreased only after acute administration of fluvoxamine. The results of this study suggest that dopaminergic medication will not affect the results of DA transporter SPET imaging with [ 123 I]FP-CIT. (orig.)

  14. Growth of electron plasma waves above and below f(p) in the electron foreshock

    Science.gov (United States)

    Cairns, Iver H.; Fung, Shing F.

    1988-01-01

    This paper investigates the conditions required for electron beams to drive wave growth significantly above and below the electron plasma frequency, f(p), by numerically solving the linear dispersion equation. It is shown that kinetic growth well below f(p) may occur over a broad range of frequencies due to the beam instability, when the electron beam is slow, dilute, and relatively cold. Alternatively, a cold or sharp feature at low parallel velocities in the distribution function may drive kinetic growth significantly below f(p). Kinetic broadband growth significantly above f(p) is explained in terms of faster warmer beams. A unified qualitative theory for the narrow-band and broad-band waves is proposed.

  15. [(123)I]FP-CIT ENC-DAT normal database

    DEFF Research Database (Denmark)

    Tossici-Bolt, Livia; Dickson, John C; Sera, Terez

    2017-01-01

    BACKGROUND: [(123)I]FP-CIT is a well-established radiotracer for the diagnosis of dopaminergic degenerative disorders. The European Normal Control Database of DaTSCAN (ENC-DAT) of healthy controls has provided age and gender-specific reference values for the [(123)I]FP-CIT specific binding ratio...... quantifications methods, BRASS and Southampton, and explores the performance of the striatal phantom calibration in their harmonisation. RESULTS: BRASS and Southampton databases comprising 123 ENC-DAT subjects, from gamma cameras with parallel collimators, were reconstructed using filtered back projection (FBP......) and iterative reconstruction OSEM without corrections (IRNC) and compared against the recommended OSEM with corrections for attenuation and scatter and septal penetration (ACSC), before and after applying phantom calibration. Differences between databases were quantified using the percentage difference...

  16. Collaboration on HiPER EU FP7 Project

    International Nuclear Information System (INIS)

    Rhee, Yong Joo; Han, Jae Min; Nam, Sung Mo; Chung, Chin Man; Lim, Chang Hwan; Cha, Yong Ho; Kwon, Duck Hee

    2011-06-01

    European Union started the HiPER project to establish a laser fusion research facility for energy production in Europe. Feasibility study and conceptual design has been performed for 2 years from 2005 and based on this study HiPER preparatory phase project has been proposed in 2007 as a EU FP7 project by 10 European countries and approved by EC. The project started in April of 2008 officially for 36 months until April of 2011. HiPER is a unique pure civilian laser fusion research facility and supported by ESFRI road map. KAERI has been participating HiPER from the feasibility study phase and still collaborating with HiPER EU FP7 project officially with the funding from the Korean government. Through this technical collaboration, participation in the joint experiments at large laser facilities has been possible and infrastructure of scientists exchange has been established Although the EU FP7 HiPER preparatory phase project ends at April of 2011 (actually it is extended until 2013 without further budget allocation fm EC) the total HiPER programme is planned to continue for more than 10 more years until the construction and commission of the fusion reactor. And KAERI also continue to participate in the HiPER programme in the future until the end of the programme

  17. Autopsy validation of 123I-FP-CIT dopaminergic neuroimaging for the diagnosis of DLB.

    Science.gov (United States)

    Thomas, Alan J; Attems, Johannes; Colloby, Sean J; O'Brien, John T; McKeith, Ian; Walker, Rodney; Lee, Lean; Burn, David; Lett, Debra J; Walker, Zuzana

    2017-01-17

    To conduct a validation study of 123 I-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane ( 123 I-FP-CIT) SPECT dopaminergic imaging in the clinical diagnosis of dementia with Lewy bodies (DLB) with autopsy as the gold standard. Patients >60 years of age with dementia who had undergone 123 I-FP-CIT imaging in research studies and who had donated their brain tissue to the Newcastle Brain Tissue Resource were included. All had structured clinical research assessments, and clinical diagnoses were applied by consensus panels using international diagnostic criteria. All underwent 123 I-FP-CIT imaging at baseline, and scans were rated as normal or abnormal by blinded raters. Patients were reviewed in prospective studies and after death underwent detailed autopsy assessment, and neuropathologic diagnoses were applied with the use of standard international criteria. Fifty-five patients (33 with DLB and 22 with Alzheimer disease) were included. Against autopsy diagnosis, 123 I-FP-CIT had a balanced diagnostic accuracy of 86% (sensitivity 80%, specificity 92%) compared with clinical diagnosis, which had an accuracy of 79% (sensitivity 87%, specificity 72%). Among patients with DLB, 10% (3 patients) met pathologic criteria for Lewy body disease but had normal 123 I-FP-CIT imaging. This large autopsy analysis of 123 I-FP-CIT imaging in dementia demonstrates that it is a valid and accurate biomarker for DLB, and the high specificity compared with clinical diagnosis (20% higher) is clinically important. The results need to be replicated with patients recruited from a wider range of settings, including movement disorder clinics and general practice. While an abnormal 123 I-FP-CIT scan strongly supports Lewy body disease, a normal scan does not exclude DLB with minimal brainstem involvement. This study provides Class I evidence that 123 I-FP-CIT dopaminergic neuroimaging accurately identifies patients with DLB. Copyright © 2016 The Author(s). Published by Wolters Kluwer

  18. The collective bands of positive parity states in odd-A (fp) shell nuclei

    International Nuclear Information System (INIS)

    Ahalpara, D.P.

    1979-01-01

    The low-lying collective bands of positive parity states in (fp) shell nuclei are described in the deformed Hartree-Fock method by projecting states of definite angular momenta from 'the lowest energy intrinsic states in (sd)sup(-1)(fp)sup(n+1) configurations. The modified Kuo-Brown effective interaction for (fp) shell and modified surface delta interaction (MSDI) for a hole in (sd) shell with a particle in (fp) shell have been used. The collective bands of states are in general well reproduced by the effective interactions. The excitation energies of the band head states are however off by about one MeV. The calculated magnetic moments of the band head j = 3/2 + states are in reasonable agreement with experiment. Using effective charges esub(p) = 1.33 e and esub(n) = 0.64 e fairly good agreement is obtained for E(2) transitions. The hindered M(1) transition strengths are reproduced to the correct order, however they are slightly higher compared to the experiment. (author)

  19. The interplay of universities and industry through the FP5 network

    International Nuclear Information System (INIS)

    Almendral, Juan A; Oliveira, J G; Lopez, L; Sanjuan, Miguel A F; Mendes, J F F

    2007-01-01

    To improve the quality of life in a modern society it is essential to reduce the distance between basic research and applications, whose crucial roles in shaping today's society prompt us to seek their understanding. Existing studies on this subject, however, have neglected the network character of the interaction between universities and industry. Here we use state-of-the-art network theory methods to analyse this interplay in the so-called Framework Programme (FP)-an initiative which sets out the priorities for the European Union's research and technological development. In particular we study in the 5th FP (FP5) the role played by companies and scientific institutions and how they contribute to enhance the relationship between research and industry. Our approach provides quantitative evidence that while firms are size hierarchically organized, universities and research organizations keep the network from falling into pieces, paving the way for an effective knowledge transfer

  20. Dopamine transporter imaging with [123I]FP-CIT SPECT: potential effects of drugs

    International Nuclear Information System (INIS)

    Booij, Jan; Kemp, Paul

    2008-01-01

    [ 123 I]N-ω-fluoropropyl-2β-carbomethoxy-3β-{4-iodophenyl}nortropane ([ 123 I]FP-CIT) single photon emission computed tomography (SPECT) is a frequently and routinely used technique to detect or exclude dopaminergic degeneration by imaging the dopamine transporter (DAT) in parkinsonian and demented patients. This technique is also used in scientific studies in humans, as well as in preclinical studies to assess the availability of DAT binding in the striatum. In routine clinical studies, but also in scientific studies, patients are frequently on medication and sometimes even use drugs of abuse. Moreover, in preclinical studies, animals will be anesthetized. Prescribed drugs, drugs of abuse, and anesthetics may influence the visual interpretation and/or quantification of [ 123 I]FP-CIT SPECT scans. Here, we discuss the basic principle of how drugs and anesthetics might influence the visual interpretation and/or quantification of [ 123 I]FP-CIT SPECT scans. We also review drugs which are likely to have a significant influence on the visual interpretation and/or quantification of [ 123 I]FP-CIT SPECT scans. Additionally, we discuss the evidence as to whether frequently prescribed drugs in parkinsonian and demented patients may have an influence on the visual interpretation and/or quantification of [ 123 I]FP-CIT SPECT scans. Finally, we discuss our recommendations as to which drugs should be ideally withdrawn before performing a [ 123 I]FP-CIT SPECT scan for routine clinical purposes. The decision to withdraw any medication must always be made by the specialist in charge of the patient's care and taking into account the pros and cons of doing so. (orig.)

  1. Striatal FP-CIT uptake differs in the subtypes of early Parkinson's disease

    International Nuclear Information System (INIS)

    Spiegel, J.; Fassbender, K.; Dillmann, U.; Hellwig, D.; Samnick, S.; Moellers, M.-O.; Kirsch, C.-M.; Jost, W.

    2007-01-01

    In idiopathic Parkinson's disease (PD), a tremor-dominant type (TDT), an akinetic-rigid type (ART), and a mixed type (MT) are distinguished. We compared cerebral [I- 123 ]FP-CIT SPECT in the PD subtypes (67 patients Hoehn and Yahr stage 1:26 with ART, 19 with MT, 22 with TDT). We measured the ratios putamen/occipital lobe binding and caudate nucleus/occipital lobe binding. Parkinsonian motor symptoms were quantified by UPDRS motor scale. In both putamen and caudate nucleus contralateral to the clinically affected body side TDT patients showed a significantly higher FP-CIT uptake than ART or MT patients (ANOVA; p 0.05). The missing correlation between striatal FP-CIT uptake and tremor suggests, that further systems besides the nigrostriatal dopaminergic system may contribute to generation of parkinsonian tremor. (author)

  2. The interplay of universities and industry through the FP5 network

    Energy Technology Data Exchange (ETDEWEB)

    Almendral, Juan A [Departamento de Fisica, Universidad Rey Juan Carlos, Tulipan s/n, 28933 Mostoles, Madrid (Spain); Oliveira, J G [Departamento de Fisica, Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Lopez, L [Departamento de IngenierIa Telematica y TecnologIa Electronica, Universidad Rey Juan Carlos, Tulipan s/n, 28933 Mostoles, Madrid (Spain); Sanjuan, Miguel A F [Departamento de Fisica, Universidad Rey Juan Carlos, Tulipan s/n, 28933 Mostoles, Madrid (Spain); Mendes, J F F [Departamento de Fisica, Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal)

    2007-06-15

    To improve the quality of life in a modern society it is essential to reduce the distance between basic research and applications, whose crucial roles in shaping today's society prompt us to seek their understanding. Existing studies on this subject, however, have neglected the network character of the interaction between universities and industry. Here we use state-of-the-art network theory methods to analyse this interplay in the so-called Framework Programme (FP)-an initiative which sets out the priorities for the European Union's research and technological development. In particular we study in the 5th FP (FP5) the role played by companies and scientific institutions and how they contribute to enhance the relationship between research and industry. Our approach provides quantitative evidence that while firms are size hierarchically organized, universities and research organizations keep the network from falling into pieces, paving the way for an effective knowledge transfer.

  3. Identification of a functional nuclear export signal in the green fluorescent protein asFP499

    International Nuclear Information System (INIS)

    Mustafa, Huseyin; Strasser, Bernd; Rauth, Sabine; Irving, Robert A.; Wark, Kim L.

    2006-01-01

    The green fluorescent protein (GFP) asFP499 from Anemonia sulcata is a distant homologue of the GFP from Aequorea victoria. We cloned the asFP499 gene into a mammalian expression vector and showed that this protein was expressed in the human lymphoblast cell line Ramos RA1 and in the embryonic kidney 293T cell line (HEK 293T). In HEK 293T cells, asFP499 was localized mainly in the cytoplasm, suggesting that the protein was excluded from the nucleus. We identified 194 LRMEKLNI 201 as a candidate nuclear export signal in asFP499 and mutated the isoleucine at position 201 to an alanine. Unlike the wildtype form, the mutant protein was distributed throughout the cytoplasm and nucleus. This is First report of a GFP that contains a functional NES

  4. TRAC-PF1 code assessment using OECD LOFT LP-FP-1 experiment

    International Nuclear Information System (INIS)

    Barbero, F.J.

    1992-04-01

    This report assesses thermal-hydraulic aspects of LOFT LP-FP-1 experiment making use of TRAC-PF1/MOD1. LP-FP-1 experiment studies the system thermal-hydraulic and core thermal response for initial and boundary conditions similar to a large-break design basis LOCA leading to fission product release from the fuel cladding gap region. It also assesses the fission product retention effectiveness of the PWR-ECCS in best estimate conditions

  5. Effects of intraluteal implants of prostaglandin E1 or E2 on angiogenic growth factors in luteal tissue of Angus and Brahman cows.

    Science.gov (United States)

    Weems, Yoshie S; Ma, Yan; Ford, Stephen P; Nett, Terry M; Vann, Rhonda C; Lewis, Andrew W; Neuendorff, Don A; Welsh, Thomas H; Randel, Ronald D; Weems, Charles W

    2014-12-01

    Previously, it was reported that intraluteal implants containing prostaglandin E1 or E2 (PGE1 and PGE2) in Angus or Brahman cows prevented luteolysis by preventing loss of mRNA expression for luteal LH receptors and luteal unoccupied and occupied LH receptors. In addition, intraluteal implants containing PGE1 or PGE2 upregulated mRNA expression for FP prostanoid receptors and downregulated mRNA expression for EP2 and EP4 prostanoid receptors. Luteal weight during the estrous cycle of Brahman cows was reported to be lesser than that of Angus cows but not during pregnancy. The objective of this experiment was to determine whether intraluteal implants containing PGE1 or PGE2 alter vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), angiopoietin-1 (ANG-1), and angiopoietin-2 (ANG-2) protein in Brahman or Angus cows. On Day 13 of the estrous cycle, Angus cows received no intraluteal implant and corpora lutea were retrieved, or Angus and Brahman cows received intraluteal silastic implants containing vehicle, PGE1, or PGE2 on Day 13 and corpora lutea were retrieved on Day 19. Corpora lutea slices were analyzed for VEGF, FGF-2, ANG-1, and ANG-2 angiogenic proteins via Western blot. Day-13 Angus cow luteal tissue served as preluteolytic controls. Data for VEGF were not affected (P > 0.05) by day, breed, or treatment. PGE1 or PGE2 increased (P Angus cows compared with Day-13 and Day-19 Angus controls but decreased (P Angus controls. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-1 in Angus luteal tissue when compared with Day-13 or Day-19 controls, but ANG-1 was decreased (P Angus Vehicle controls when compared with Day-13 Angus controls, which was prevented (P Angus cows. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-2 in Brahman cows. PGE1 or PGE2 may alter cow luteal FGF-2, ANG-1, or ANG-2 but not VEGF to prevent luteolysis; however, species or breed differences may exist. Published by Elsevier Inc.

  6. Safety and efficacy of the prostaglandin D2 receptor antagonist AMG 853 in asthmatic patients.

    Science.gov (United States)

    Busse, William W; Wenzel, Sally E; Meltzer, Eli O; Kerwin, Edward M; Liu, Mark C; Zhang, Nan; Chon, Yun; Budelsky, Alison L; Lin, Joseph; Lin, Shao-Lee

    2013-02-01

    The D-prostanoid receptor and the chemoattractant receptor homologous molecule expressed on T(H)2 cells (CRTH2) are implicated in asthma pathogenesis. AMG 853 is a potent, selective, orally bioavailable, small-molecule dual antagonist of human D-prostanoid and CRTH2. We sought to determine the efficacy and safety of AMG 853 compared with placebo in patients with inadequately controlled asthma. Adults with moderate-to-severe asthma were randomized to placebo; 5, 25, or 100 mg of oral AMG 853 twice daily; or 200 mg of AMG 853 once daily for 12 weeks. All patients continued their inhaled corticosteroids. Long-acting β-agonists were not allowed during the treatment period. Allowed concomitant medications included short-acting β-agonists and a systemic corticosteroid burst for asthma exacerbation. The primary end point was change in total Asthma Control Questionnaire score from baseline to week 12. Secondary and exploratory end points included FEV(1), symptom scores, rescue short-acting β-agonist use, and exacerbations. Among treated patients, no effect over placebo (n = 79) was observed in mean changes in Asthma Control Questionnaire scores at 12 weeks (placebo, -0.492; range for AMG 853 groups [n = 317], -0.444 to -0.555). No significant differences between the active and placebo groups were observed for secondary end points. The most commonly reported adverse events were asthma, upper respiratory tract infection, and headache; 9 patients experienced serious adverse events, all of which were deemed unrelated to study treatment by the investigator. AMG 853 as an add-on to inhaled corticosteroid therapy demonstrated no associated risks but was not effective at improving asthma symptoms or lung function in patients with inadequately controlled moderate-to-severe asthma. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  7. PGE2 maintains the tone of the guinea pig trachea through a balance between activation of contractile EP1 receptors and relaxant EP2 receptors

    Science.gov (United States)

    Säfholm, J; Dahlén, S-E; Delin, I; Maxey, K; Stark, K; Cardell, L-O; Adner, M

    2013-01-01

    Background and Purpose The guinea pig trachea (GPT) is commonly used in airway pharmacology. The aim of this study was to define the expression and function of EP receptors for PGE2 in GPT as there has been ambiguity concerning their role. Experimental Approach Expression of mRNA for EP receptors and key enzymes in the PGE2 pathway were assessed by real-time PCR using species-specific primers. Functional studies of GPT were performed in tissue organ baths. Key Results Expression of mRNA for the four EP receptors was found in airway smooth muscle. PGE2 displayed a bell-shaped concentration–response curve, where the initial contraction was inhibited by the EP1 receptor antagonist ONO-8130 and the subsequent relaxation by the EP2 receptor antagonist PF-04418948. Neither EP3 (ONO-AE5-599) nor EP4 (ONO-AE3-208) selective receptor antagonists affected the response to PGE2. Expression of COX-2 was greater than COX-1 in GPT, and the spontaneous tone was most effectively abolished by selective COX-2 inhibitors. Furthermore, ONO-8130 and a specific PGE2 antibody eliminated the spontaneous tone, whereas the EP2 antagonist PF-04418948 increased it. Antagonists of other prostanoid receptors had no effect on basal tension. The relaxant EP2 response to PGE2 was maintained after long-term culture, whereas the contractile EP1 response showed homologous desensitization to PGE2, which was prevented by COX-inhibitors. Conclusions and Implications Endogenous PGE2, synthesized predominantly by COX-2, maintains the spontaneous tone of GPT by a balance between contractile EP1 receptors and relaxant EP2 receptors. The model may be used to study interactions between EP receptors. PMID:22934927

  8. Diagnostic accuracy of combined FP-CIT, IBZM, and MIBG scintigraphy in the differential diagnosis of degenerative parkinsonism: a multidimensional statistical approach.

    Science.gov (United States)

    Südmeyer, Martin; Antke, Christina; Zizek, Tanja; Beu, Markus; Nikolaus, Susanne; Wojtecki, Lars; Schnitzler, Alfons; Müller, Hans-Wilhelm

    2011-05-01

    In vivo molecular imaging of pre- and postsynaptic nigrostriatal neuronal degeneration and sympathetic cardiac innervation with SPECT is used to distinguish idiopathic Parkinson disease (PD) from atypical parkinsonian disorder (APD). However, the diagnostic accuracy of these imaging approaches as stand-alone procedures is often unsatisfying. The aim of this study was therefore to evaluate to which extent diagnostic accuracy can be increased by their combined use together with a multidimensional statistical algorithm. The SPECT radiotracers (123)I-(S)-2-hydroxy-3-iodo-6-methoxy-N-[1-ethyl-2-pyrrodinyl)-methyl]benzamide (IBZM), (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropan (FP-CIT), and meta-(123)I-iodobenzylguanidine (MIBG) were used to assess striatal postsynaptic D(2) receptor binding, striatal presynaptic dopamine transporter binding, and myocardial adrenergic innervation, respectively. Thirty-one PD and 17 APD patients were prospectively investigated. PD and APD diagnoses were established using consensus criteria and reevaluated after 37.4 ± 12.4 and 26 ± 11.6 mo in PD and APD, respectively. Test accuracy (TA) for PD-APD differentiation was computed for all logical (Boolean) combinations of imaging modalities by receiver-operating-characteristic analysis--that is, after multidimensional optimization of cutoff values. Analysis showed moderate TA for PD-APD differentiation using each molecular approach alone (IBZM, 79%; MIBG, 73%; and FP-CIT, 73%). For combined use, the highest TA resulted under the assumption that at least 2 of the 3 biologic markers had to be positive for APD using the following cutoff values: 1.46 or less for IBZM, less than 2.10 for FP-CIT, and greater than 1.43 for MIBG. This algorithm distinguished APD from PD with a sensitivity of 94%, specificity of 94% (TA, 94%), positive predictive value of 89%, and negative predictive value of 97%. Results suggest that the multidimensional combination of FP-CIT, IBZM, and MIBG

  9. Dopamine transporter imaging with [{sup 123}I]FP-CIT SPECT: potential effects of drugs

    Energy Technology Data Exchange (ETDEWEB)

    Booij, Jan [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands); Kemp, Paul [Southampton University Hospitals Trust, Department of Nuclear Medicine, Southampton (United Kingdom)

    2008-02-15

    [{sup 123}I]N-{omega}-fluoropropyl-2{beta}-carbomethoxy-3{beta}-{l_brace}4-iodophenyl{r_brace}nortropane ([{sup 123}I]FP-CIT) single photon emission computed tomography (SPECT) is a frequently and routinely used technique to detect or exclude dopaminergic degeneration by imaging the dopamine transporter (DAT) in parkinsonian and demented patients. This technique is also used in scientific studies in humans, as well as in preclinical studies to assess the availability of DAT binding in the striatum. In routine clinical studies, but also in scientific studies, patients are frequently on medication and sometimes even use drugs of abuse. Moreover, in preclinical studies, animals will be anesthetized. Prescribed drugs, drugs of abuse, and anesthetics may influence the visual interpretation and/or quantification of [{sup 123}I]FP-CIT SPECT scans. Here, we discuss the basic principle of how drugs and anesthetics might influence the visual interpretation and/or quantification of [{sup 123}I]FP-CIT SPECT scans. We also review drugs which are likely to have a significant influence on the visual interpretation and/or quantification of [{sup 123}I]FP-CIT SPECT scans. Additionally, we discuss the evidence as to whether frequently prescribed drugs in parkinsonian and demented patients may have an influence on the visual interpretation and/or quantification of [{sup 123}I]FP-CIT SPECT scans. Finally, we discuss our recommendations as to which drugs should be ideally withdrawn before performing a [{sup 123}I]FP-CIT SPECT scan for routine clinical purposes. The decision to withdraw any medication must always be made by the specialist in charge of the patient's care and taking into account the pros and cons of doing so. (orig.)

  10. Synthesis and quality control of 18F-β-FP-CIT as a dopamine transporter imaging agent

    International Nuclear Information System (INIS)

    Tang Ganghua; Tang Xiaolan; Wang Mingfang; Huang Zuhan

    2002-01-01

    Objective: To develop 18 F-N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophenyl) nortropane ( 18 F-β-FP-CIT) as dopamine transporter imaging agent. Methods: The labelling of 18 F-β-FP-CIT was performed via a two-step synthesis. The 18 F-fluoropropyl bromide was prepared through a nucleophilic substitution by the use of the aminopolyether potassium complex (K/K222) +18 F - as a phase-transfer reagent, and then by N-fluoroalkylation of 2-β-carbomethoxy-3-β-(4-iodophenyl) nortropane (nor-β-CIT) with 18 F-fluoropropyl bromide the 18 F-β-FP-CIT was formed. Contents and analytical methods of quality control for 18 F-β-FP-CIT were investigated and the main quality criteria were achieved through strict control of the determining parameters by standard procedures. Results: The mean overall radiochemical yield from starting 18 F-fluoride was about 8%, the total radiochemical synthesis time was about 90-110 min, and the radiochemical purity was better than 99% by HPLC and TLC. Tests on sterility and apyrogenicity of 18 F-β-FP-CIT obtained by standard procedures were negative, and tests on other main quality criteria met the requirements of the local pharmacopoeia. Conclusion: 18 F-β-FP-CIT injection can be used in the animal and human PET study

  11. Preparation of lumped fission product (FP) cross sections for a multigroup library

    International Nuclear Information System (INIS)

    Ono, S.; Corcuera, R.P.

    1984-01-01

    A method for the calculation of lumped Fission Product (FP) cross sections has been developed. The group constants fo each nuclide are generated by NJOY code, based on ENDF/B-V data. In this first version, cross section of 28 nuclides are lumped for typical characteristics of Binary Breeder Reactor (BBR). One energy group calculations are made for a 1000 MWe fast reactor to verify the influence of burnup, number of FP and fuel composition on the lumped fission product cross sections. (Author) [pt

  12. JENDL FP decay data file 2000 and the beta-decay theory

    International Nuclear Information System (INIS)

    Yoshida, Tadashi; Katakura, Jun Ichi; Tachibana, Takahiro

    2002-01-01

    JENDL FP Decay Data File 2000 has been developed as one of the special purpose files of the Japanese Evaluated Nuclear Data Library (JENDL), which constitutes a versatile nuclear data basis for science and technology. In the format of ENDF-6 this file includes the decay data for 1087 unstable fission product (FP) nuclides and 142 stable nuclides as their daughters. The primary purpose of this file is to use in the summation calculation of FP decay heat, which plays a critical role in nuclear safety analysis; the loss-of-coolant accident analysis of reactors, for example. The data for a given nuclide are its decay modes, the Q value, the branching ratios, the average energies released in the form of beta- and gamma-rays per decay, and their spectral data. The primary source of the decay data adopted here is the ENSDF (Evaluated Nuclear Structure Data File). The data in ENSDF, however, cover only the measured values. The data of the short-lived nuclides, which are essential for the decay heat calculations at short cooling times, are often fully lacking or incomplete even if they exist. This is mainly because of their short half-life nature. For such nuclides a theoretical model calculation is applied in order to fill the gaps between the true and the experimentally known decay schemes. In practice we have to predict the average decay energies and the spectral data for a lot of short-lived FPs by use of beta-decay theories. Thus the beta-decay theory plays a very important role in generating the FP decay data file

  13. Rotational order–disorder structure of fluorescent protein FP480

    International Nuclear Information System (INIS)

    Pletnev, Sergei; Morozova, Kateryna S.; Verkhusha, Vladislav V.; Dauter, Zbigniew

    2009-01-01

    An analysis of the rotational order–disorder structure of fluorescent protein FP480 is presented. In the last decade, advances in instrumentation and software development have made crystallography a powerful tool in structural biology. Using this method, structural information can now be acquired from pathological crystals that would have been abandoned in earlier times. In this paper, the order–disorder (OD) structure of fluorescent protein FP480 is discussed. The structure is composed of tetramers with 222 symmetry incorporated into the lattice in two different ways, namely rotated 90° with respect to each other around the crystal c axis, with tetramer axes coincident with crystallographic twofold axes. The random distribution of alternatively oriented tetramers in the crystal creates a rotational OD structure with statistically averaged I422 symmetry, although the presence of very weak and diffuse additional reflections suggests that the randomness is only approximate

  14. Improvement and Validation of an Aerosol Deposition Model in the GAMMA-FP, a Fission Product Analysis Module for VHTRs

    International Nuclear Information System (INIS)

    Yoon, Churl; Lim, Hong Sik

    2013-01-01

    GAMMA-FP (GAs Multicomponent Mixture Analysis-Fission Products module), consists of gaseous and aerosol fission product analysis modules. The aerosol FP module adopts a multi-component and multi-sectional aerosol analysis model that has been developed based on the MAEROS model. For the first work of FP module development, the MAEROS model has been implemented and examined against some analytic solutions and experimental data by Yoo et al. An aerosol transport model was developed and implemented in the GAMMA-FP code, and verified. In this study, the aerosol deposition model in the GAMMA-FP code was improved by adopting recent achievements, and was validated against an experimental data available. The aerosol deposition model in the GAMMA-FP code has been improved and successfully validated against the STORM SR-11 deposition test. The simulation with the improved deposition model predicted the matched results with the experimental data well. For future studies, the aerosol deposition model by flow irregularities will be implemented and validated against the TRANSAT bend effect test

  15. Improvement and Validation of an Aerosol Deposition Model in the GAMMA-FP, a Fission Product Analysis Module for VHTRs

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Churl; Lim, Hong Sik [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-10-15

    GAMMA-FP (GAs Multicomponent Mixture Analysis-Fission Products module), consists of gaseous and aerosol fission product analysis modules. The aerosol FP module adopts a multi-component and multi-sectional aerosol analysis model that has been developed based on the MAEROS model. For the first work of FP module development, the MAEROS model has been implemented and examined against some analytic solutions and experimental data by Yoo et al. An aerosol transport model was developed and implemented in the GAMMA-FP code, and verified. In this study, the aerosol deposition model in the GAMMA-FP code was improved by adopting recent achievements, and was validated against an experimental data available. The aerosol deposition model in the GAMMA-FP code has been improved and successfully validated against the STORM SR-11 deposition test. The simulation with the improved deposition model predicted the matched results with the experimental data well. For future studies, the aerosol deposition model by flow irregularities will be implemented and validated against the TRANSAT bend effect test.

  16. Preparation of a dopamine transporter imaging agent 18F-FP-β-CIT and its biodistribution in rat brain

    International Nuclear Information System (INIS)

    Chen Zhengping; Wu Chunying; Li Xiaomin; Zhang Tongxing; Wang Songpei; Lu Chunxiong; Fu Ronggeng; Zhang Zhengwei; Guan Yihui

    2003-01-01

    Objective: To develop a simple and easy protocol of preparing 18 F-N-3-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (FP-β-CIT) as a dopamine transporter imaging agent, and to study the distribution of this agent in rat brain. Methods: 18 F-FP-β-CIT was prepared by direct reaction in CH 3 CN between K 18 F and the labeling precursor, N-(3-(mesyloxy) propyl )-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (MsOP-CIT), in which Kryptofix 222 was used as phase transfer catalyst. 18 F-FP-β-CIT was purified through a Sep-Pak SiO 2 cartridge and eluted with ethyl ether. The purified 18 F-FP-β-CIT was injected into the rat's tail vein. These rats were sacrificed by cervical dislocation at different time points (5, 30, 60, 120, 180 min) after injection. The brain tissue of interest was removed, weighed, and radiocounted. Results: The radiochemical purity of 18 F-FP-β-CIT was over 95%, and the radiochemical yield from starting 18 F-fluoride was about 10%. 18 F-FP-β-CIT was absorbed rapidly in rat brain and was cleaned gradually (1.49, 0.59, 0.31, 0.21, 0.17%ID at 5, 30, 60, 120, 180 min, respectively). Radiouptake of striatum was more than that of other tissues and was cleaned slower than in other tissues at 60 min. Ratios of radiouptake of striatum /cerebellum were 1.75, 3.38, 3.73, 3.71 and 3.20 at 5, 30, 60, 120, 180 min, respectively. Conclusions: 18 F-FP-β-CIT is synthesized by a one-step protocol in which the preparative high performance liquid chromatography is not necessary in purifying procedure. The dominant distribution of 18 F-FP-β-CIT in rat striatum indicates that it is a potential dopamine transporter imaging agent

  17. Clinical features and 123I-FP-CIT SPECT imaging in drug-induced parkinsonism and Parkinson's disease

    International Nuclear Information System (INIS)

    Diaz-Corrales, Francisco J.; Escobar-Delgado, Teresa; Sanz-Viedma, Salome; Garcia-Solis, David; Mir, Pablo

    2010-01-01

    To determine clinical predictors and accuracy of 123 I-FP-CIT SPECT imaging in the differentiation of drug-induced parkinsonism (DIP) and Parkinson's disease (PD). Several clinical features and 123 I-FP-CIT SPECT images in 32 patients with DIP, 25 patients with PD unmasked by antidopaminergic drugs (PDu) and 22 patients with PD without a previous history of antidopaminergic treatment (PDc) were retrospectively evaluated. DIP and PD shared all clinical features except symmetry of parkinsonian signs which was more frequently observed in patients with DIP (46.9%) than in patients with PDu (16.0%, p 123 I-FP-CIT SPECT images were normal in 29 patients with DIP (90.6%) and abnormal in all patients with PD, and this imaging technique showed high levels of accuracy. DIP and PD are difficult to differentiate based on clinical signs. The precision of clinical diagnosis could be reliably enhanced by 123 I-FP-CIT SPECT imaging. (orig.)

  18. Supply chain management using fp-growth algorithm for medicine distribution

    Science.gov (United States)

    Wahana, A.; Maylawati, D. S.; Irfan, M.; Effendy, H.

    2018-03-01

    Distribution of drugs evenly in accordance with the needs of Public Health Center (Puskesmas) become one of the responsibilities by the Health Office in Indonesia. This study aims to provide recommendations for distribution of drugs from the Department of Health according to the needs of each Puskesmas. Because often the distribution of drugs is not in accordance with the needs of medicines stock of each Puskesmas. This causes the possibility of drug stock void in Puskesmas in need, while there is excess stock of drugs in Puskesmas that do not need. Supply Chain Management (SCM) is applied as a controlling drug stock at Puskesmas in order to avoid drug vacuum or excess drug that eventually unused. In addition, the Frequent Pattern Growth (FP-Growth) algorithm that generates frequent item sets is used to provide drug distribution recommendations by looking at the highest frequency of drug occurrences and frequent drug frequencies. Based on testing black box system conducted in Health Office Purwakarta regency of Indonesia which oversees 20 Puskesmas with 100 data of drug distribution transactions, it can be concluded that system functionality is running well and SCM successfully implemented to arrange distribution process of medicine well. Furthermore FP-Growth algorithm was able to provide recommendations for distribution of drugs with a high success rate. This is evidenced by the test results with various combinations of input parameters, FP-Growth is able to produce the right frequent item sets.

  19. Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers

    International Nuclear Information System (INIS)

    Lavalaye, J.; Booij, J.; Reneman, L.; Habraken, J.B.A.; Royen, E.A. van

    2000-01-01

    Dopamine transporter imaging is a valuable tool to investigate the integrity of the dopaminergic neurons. To date, several reports have shown an age-associated decline in dopamine transporters in healthy volunteers. Although animal studies suggest an effect of gender on dopamine transporter density, this gender effect has not yet been confirmed in human studies. To study the influence of age and gender on dopamine transporter imaging in healthy volunteers, we performed single-photon emission tomography imaging with [ 123 I]FP-CIT to quantify dopamine transporters. Forty-five healthy volunteers (23 males and 22 females) were included, ranging in age from 18 to 83 years. SPET imaging was performed 3 h after injection of ±110 MBq [ 123 I]FP-CIT. An operator-independent volume of interest analysis was used for quantification of [ 123 I]FP-CIT binding in the striatum. The ratio of specific striatal to non-specific [ 123 I]FP-CIT binding was found to decrease significantly with age. Moreover, we found a high variance in [ 123 I]FP-CIT binding in young adults. Finally, females were found to have significantly higher [ 123 I]FP-CIT binding ratios than males. This effect of gender on [ 123 I]FP-CIT binding ratios was not related to age. The results of this study are consistent with findings from previous studies, which showed that dopamine transporter density declines with age. The intriguing finding of a higher dopamine transporter density in females than in males is in line with findings from animal studies. (orig.)

  20. Theoretical spectroscopy and the fp shell

    International Nuclear Information System (INIS)

    Poves, A.; Zuker, A.

    1980-01-01

    The recently developed quasiconfiguration method is applied to fp shell nuclei. Second order degenerate perturbation theory is shown to be sufficient to produce, for low lying states, the same results as large diagonalizations in the f(7/2)p(3/2)p(1/2)f(5/2)sup(n) full space. due to the operation of linked cluster mechanisms. Realistic interactions with minimal monopole changes are shown to be successful in reproducing spectra, binding energies, quadrupole moments and transition rates. Large shell model spaces are seen to exhibit typical many body behaviour. Quasiconfigurations allow insight into the underlying coupling schemes

  1. The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism

    International Nuclear Information System (INIS)

    Booij, J.; Speelman, J.DE.; Horstink, M. W.I.M.; Wolters, E.C.

    2001-01-01

    , and in three cases no conclusive diagnosis was established, but presynaptic parkinsonism was excluded clinically. A clinical diagnosis of presynaptic parkinsonism was established in two cases: one case of multiple system atrophy (in this patient loss of dopamine D 2 receptors was found with [ 123 I]iodobenzamide SPET performed 2 weeks after [ 123 I]FP-CIT imaging) and one case of Parkinson's disease. Our data suggest that the positive predictive value of [ 123 I]FP-CIT imaging is very high, and although the negative predictive value is lower, dopamine transporter imaging offers the prospect of a quick, objective method to confirm or exclude presynaptic parkinsonism in inconclusive cases. (orig.)

  2. Developing the "120 by 20" goal for the Global FP2020 Initiative.

    Science.gov (United States)

    Brown, Win; Druce, Nel; Bunting, Julia; Radloff, Scott; Koroma, Desmond; Gupta, Srishti; Siems, Brian; Kerrigan, Monica; Kress, Dan; Darmstadt, Gary L

    2014-03-01

    This report describes the purpose for developing a quantitative goal for the London Summit on Family Planning held in July 2012, the methodology behind its formulation, and the lessons learned in the process. The London Summit has evolved into the global initiative known as FP2020, and the goal has become "120 by 20," or reaching 120 million additional users of modern contraceptive methods by 2020 in the world's poorest countries. The success of FP2020 will first be evaluated on the basis of quantitative verification to determine that the "120 by 20" goal was reached. More important, however, is the extent to which the goal today serves as a global rallying cry to mobilize resources and leadership around current family planning programs, with a focus on voluntary family planning and quality of care, and with an emphasis on meeting girls' and women's unmet needs and their right to practice contraception. We hope this article provides greater transparency and understanding of the FP2020 goal, and that the global goal spurs annual monitoring of progress toward national goals in the world's poorest countries. © 2014 The Population Council, Inc.

  3. High spin structure of 35Cl and the sd-fp shell gap

    International Nuclear Information System (INIS)

    Kshetri, Ritesh; Saha Sarkar, M.; Ray, Indrani; Banerjee, P.; Sarkar, S.; Raut, Rajarshi; Goswami, A.; Chatterjee, J.M.; Chattopadhyay, S.; Datta Pramanik, U.; Mukherjee, A.; Dey, C.C.; Bhattacharya, S.; Dasmahapatra, B.; Bhowal, Samit; Gangopadhyay, G.; Datta, P.; Jain, H.C.; Bhowmik, R.K.; Muralithar, S.; Singh, R.P.; Kumar, R.

    2007-01-01

    The high spin states of 35 Cl have been studied by in-beam γ-spectroscopy following the fusion-evaporation reaction 12 C( 28 Si,αp) 35 Cl at E lab =70 and 88 MeV, using the Indian National Gamma (Clover) Array (INGA). Lifetimes of six new excited states have been estimated for the first time. To understand the underlying structure of the levels and transition mechanisms, experimental results have been compared with those from the large basis cross-shell shell model calculations. Involvement of orbitals from fp shell and squeezing of the sd-fp shell gap seem to be essential for reliable reproduction of high spin states

  4. Protein kinase C-related kinase 1 and 2 play an essential role in thromboxane-mediated neoplastic responses in prostate cancer

    OpenAIRE

    O'Sullivan, Aine G.; Mulvaney, Eamon P.; Hyland, Paula B.; Kinsella, B. Therese

    2015-01-01

    The prostanoid thromboxane (TX) A2 is increasingly implicated in neoplastic progression, including prostate cancer (PCa). Mechanistically, we recently identified protein kinase C-related kinase (PRK) 1 as a functional interactant of both the TP? and TP? isoforms of the human T prostanoid receptor (TP). The interaction with PRK1 was not only essential for TP?/TP?-induced PCa cell migration but also enabled the TXA2-TP axis to induce phosphorylation of histone H3 at Thr11 (H3Thr11), an epigenet...

  5. File Specification for GEOS-5 FP (Forward Processing)

    Science.gov (United States)

    Lucchesi, R.

    2013-01-01

    The GEOS-5 FP Atmospheric Data Assimilation System (GEOS-5 ADAS) uses an analysis developed jointly with NOAA's National Centers for Environmental Prediction (NCEP), which allows the Global Modeling and Assimilation Office (GMAO) to take advantage of the developments at NCEP and the Joint Center for Satellite Data Assimilation (JCSDA). The GEOS-5 AGCM uses the finite-volume dynamics (Lin, 2004) integrated with various physics packages (e.g, Bacmeister et al., 2006), under the Earth System Modeling Framework (ESMF) including the Catchment Land Surface Model (CLSM) (e.g., Koster et al., 2000). The GSI analysis is a three-dimensional variational (3DVar) analysis applied in grid-point space to facilitate the implementation of anisotropic, inhomogeneous covariances (e.g., Wu et al., 2002; Derber et al., 2003). The GSI implementation for GEOS-5 FP incorporates a set of recursive filters that produce approximately Gaussian smoothing kernels and isotropic correlation functions. The GEOS-5 ADAS is documented in Rienecker et al. (2008). More recent updates to the model are presented in Molod et al. (2011). The GEOS-5 system actively assimilates roughly 2 × 10(exp 6) observations for each analysis, including about 7.5 × 10(exp 5) AIRS radiance data. The input stream is roughly twice this volume, but because of the large volume, the data are thinned commensurate with the analysis grid to reduce the computational burden. Data are also rejected from the analysis through quality control procedures designed to detect, for example, the presence of cloud. To minimize the spurious periodic perturbations of the analysis, GEOS-5 FP uses the Incremental Analysis Update (IAU) technique developed by Bloom et al. (1996). More details of this procedure are given in Appendix A. The assimilation is performed at a horizontal resolution of 0.3125-degree longitude by 0.25- degree latitude and at 72 levels, extending to 0.01 hPa. All products are generated at the native resolution of the

  6. Direct comparison of FP-CIT SPECT and F-DOPA PET in patients with Parkinson's disease and healthy controls

    International Nuclear Information System (INIS)

    Eshuis, S.A.; Maguire, R.P.; Leenders, K.L.; Jager, P.L.; Jonkman, S.; Dierckx, R.A.

    2009-01-01

    Diagnosing Parkinson's disease (PD) on clinical grounds may be difficult, especially in the early stages of the disease. F-DOPA PET and FP-CIT SPECT scans are able to determine presynaptic dopaminergic activity in different ways. The aim of this study was to determine and compare the sensitivity and specificity of the two methods in the detection of striatal dopaminergic deficits in the same cohort of PD patients and healthy controls. Movement disorder specialists recruited 11 patients with early-stage PD and 17 patients with advanced PD. The patients underwent both an FP-CIT SPECT scan and an F-DOPA PET scan. In addition, 10 FP-CIT SPECT scans or 10 F-DOPA PET scans were performed in 20 healthy controls. A template with regions of interest was used to sample tracer activity of the caudate, putamen and a reference region in the brain. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were determined in the controls. The sensitivity and specificity of both scanning methods were calculated. FP-CIT SPECT and F-DOPA PET scans were both able to discriminate PD patients from healthy controls. For the early phases of the disease, sensitivity and specificity of the contralateral striatal and putaminal uptake of FP-CIT and F-DOPA was 100%. When only caudate uptake was considered, the specificities were 100% and 90% for FP-CIT and F-DOPA, respectively, while the sensitivity was 91% for both scanning techniques. FP-CIT SPECT and F-DOPA PET scans are both able to diagnose presynaptic dopaminergic deficits in early phases of PD with excellent sensitivity and specificity. (orig.)

  7. The role of boric acid in the Phebus-FP tests

    International Nuclear Information System (INIS)

    Bowsher, B.R.

    1991-12-01

    The data in this report should enable proposed methods for the introduction of boric acid into the Phebus-FP tests to be assessed. Boric acid chemistry is reviewed in the condensed, vapour and aqueous phases. The chemistry of concentrated aqueous solutions of boric acid is complex, involving polyborate species resulting in enhanced acidities. Equations are presented that allow the partition of boric acid between the vapour and aqueous phase to be calculated at different boric acid concentrations. The volatility of boric acid is enhanced significantly in the presence of steam. Equations are given that allow the effective vapour pressure of boric acid to be determined as functions of the water vapour pressure for temperatures in the range from 723 to 1000 o C. These data are confirmed by experimental studies designed to simulate specific aspects of the conditions in the Phebus-FP tests. (author)

  8. Utilisation des modules ATM pour le projet FP420

    CERN Document Server

    Renaglia, T

    2006-01-01

    Le but de cette note est de résumer les premières caractéristiques de l'intégration de 2 modules ATM pour le projet FP420 (voir note technique EDMS n° 743628) ainsi que la liste des problèmes découverts à ce jour sur l

  9. Acute administration of haloperidol does not influence 123I-FP-CIT binding to the dopamine transporter

    NARCIS (Netherlands)

    Booij, Jan; van Loon, Guus; de Bruin, Kora; Voorn, Pieter

    2014-01-01

    A recent (123)I-FP-CIT ((123)-I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane) SPECT study on rats suggested that a single 1 mg/kg dose of the antipsychotic haloperidol induces enough dopamine release to compete with (123)I-FP-CIT for binding to the dopamine transporter. Taking into

  10. Unmet Need for Contraception among Clients of FP/HIV Integrated ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    1 Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina at Chapel Hill,. Chapel Hill ... Keywords: Partner opposition, contraceptive use, HIV/FP service integration, Nigeria ..... new programs/policies that consider gender and cultural influence on family planning service.

  11. Dopamine transporter SPECT using fast kinetic ligands: 123I-FP-β-CIT versus 99mTc-TRODAT-1

    International Nuclear Information System (INIS)

    Laere, K. van; Ceuninck, L. de; Eynden, J. van den; Dupont, P.; Mortelmans, L.; Dom, R.; Vanbilloen, H.; Cleynhens, J.; Bormans, G.; Verbruggen, A.

    2004-01-01

    A comparative study was carried out on two promising presynaptic dopamine transporter single-photon emission tomography (SPECT) radioligands with a fast pharmacokinetic profile, 123 I-FP-β-CIT (FP) and 99m Tc-TRODAT-1 (TR), in order to assess their differential diagnostic power in early parkinsonism and their sensitivity for detection of disease progression. This cross-sectional study was conducted on 96 patients with early-stage parkinsonism referred in a tertiary clinical setting. Mean disease duration was 2.0±1.3 years, and patients had a modified Hoehn and Yahr (H and Y) stage of 1-2 (average 1.2). Forty-seven patients received TR, and 49 received FP. In both groups, ten patients with normal presynaptic function were included as a control population; all other patients were clinically diagnosed as having idiopathic Parkinson's disease. Groups were matched for gender, age, disease duration and modified H and Y stage. Triple-head gamma camera SPECT was analysed using a semiquantitative index of transporter binding (BI). Discriminant analysis with cross-validation resulted in a maximal classification accuracy for FP of 93% (sensitivity 95% and specificity 86%) for the contralateral putamen BI. For TR, the corresponding values were 87% accuracy, 92% sensitivity and 70% specificity. For FP, disease duration was correlated with both the putamen BI (-8.8%/year, ρ=-0.41, P=0.025) and the putamen/caudate ratio (-7.4%/year, ρ=-0.51, P=0.004), but for TR no significant correlation was found (all P values >0.5). In conclusion, both FP and TR show high sensitivity in a clinically relevant setting, but FP has superior accuracy for early differential diagnosis of idiopathic parkinsonism and non-degenerative extrapyramidal disorders, as well as better sensitivity for disease follow-up. (orig.)

  12. Tachykinin NK2 receptor and functional mechanisms in human colon: changes with indomethacin and in diverticular disease and ulcerative colitis.

    Science.gov (United States)

    Burcher, Elizabeth; Shang, Fei; Warner, Fiona J; Du, Qin; Lubowski, David Z; King, Denis W; Liu, Lu

    2008-01-01

    Neurokinin A (NKA) is an important spasmogen in human colon. We examined inflammatory disease-related changes in the tachykinin NK(2) receptor system in human sigmoid colon circular muscle, using functional, radioligand binding, and quantitative reverse transcription-polymerase chain reaction methods. In circular muscle strips, indomethacin enhanced contractile responses to NKA (p diverticular disease (DD) specimens, indicating NK(2) receptor-mediated release of relaxant prostanoids. Contractile responses to both tachykinins were reduced in strips from DD (p disease patients, demonstrating that the change in responsiveness to tachykinins in disease is specifically mediated by the NK(2) receptor. In membranes from UC specimens, receptor affinity for (125)I-NKA (median K(D) 0.91 nM, n = 16) was lower (p disease-related changes in receptor number (B(max)) were found (mean, 2.0-2.5 fmol/mg of wet weight tissue), suggesting that the reduced contractile responses in disease are not due to a loss of receptor number. Different mechanisms may account for the reduced contractility in DD compared with UC. A gender-related difference in receptor density was seen in controls, with B(max) lower in females (1.77 fmol/mg, n = 15) than in males (2.60 fmol/mg, n = 25, p = 0.01). In contrast, no gender-related differences were seen in NK(2) receptor mRNA in control colonic muscle, indicating that the gender difference is a post-translational event.

  13. GPCR-I-TASSER: A Hybrid Approach to G Protein-Coupled Receptor Structure Modeling and the Application to the Human Genome.

    Science.gov (United States)

    Zhang, Jian; Yang, Jianyi; Jang, Richard; Zhang, Yang

    2015-08-04

    Experimental structure determination remains difficult for G protein-coupled receptors (GPCRs). We propose a new hybrid protocol to construct GPCR structure models that integrates experimental mutagenesis data with ab initio transmembrane (TM) helix assembly simulations. The method was tested on 24 known GPCRs where the ab initio TM-helix assembly procedure constructed the correct fold for 20 cases. When combined with weak homology and sparse mutagenesis restraints, the method generated correct folds for all the tested cases with an average Cα root-mean-square deviation 2.4 Å in the TM regions. The new hybrid protocol was applied to model all 1,026 GPCRs in the human genome, where 923 have a high confidence score and are expected to have correct folds; these contain many pharmaceutically important families with no previously solved structures, including Trace amine, Prostanoids, Releasing hormones, Melanocortins, Vasopressin, and Neuropeptide Y receptors. The results demonstrate new progress on genome-wide structure modeling of TM proteins. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn

    Science.gov (United States)

    Majed, Batoule H.

    2012-01-01

    Prostacyclin (PGI2) is a member of the prostanoid group of eicosanoids that regulate homeostasis, hemostasis, smooth muscle function and inflammation. Prostanoids are derived from arachidonic acid by the sequential actions of phospholipase A2, cyclooxygenase (COX), and specific prostaglandin (PG) synthases. There are two major COX enzymes, COX1 and COX2, that differ in structure, tissue distribution, subcellular localization, and function. COX1 is largely constitutively expressed, whereas COX2 is induced at sites of inflammation and vascular injury. PGI2 is produced by endothelial cells and influences many cardiovascular processes. PGI2 acts mainly on the prostacyclin (IP) receptor, but because of receptor homology, PGI2 analogs such as iloprost may act on other prostanoid receptors with variable affinities. PGI2/IP interaction stimulates G protein-coupled increase in cAMP and protein kinase A, resulting in decreased [Ca2+]i, and could also cause inhibition of Rho kinase, leading to vascular smooth muscle relaxation. In addition, PGI2 intracrine signaling may target nuclear peroxisome proliferator-activated receptors and regulate gene transcription. PGI2 counteracts the vasoconstrictor and platelet aggregation effects of thromboxane A2 (TXA2), and both prostanoids create an important balance in cardiovascular homeostasis. The PGI2/TXA2 balance is particularly critical in the regulation of maternal and fetal vascular function during pregnancy and in the newborn. A decrease in PGI2/TXA2 ratio in the maternal, fetal, and neonatal circulation may contribute to preeclampsia, intrauterine growth restriction, and persistent pulmonary hypertension of the newborn (PPHN), respectively. On the other hand, increased PGI2 activity may contribute to patent ductus arteriosus (PDA) and intraventricular hemorrhage in premature newborns. These observations have raised interest in the use of COX inhibitors and PGI2 analogs in the management of pregnancy-associated and neonatal

  15. Quantification of Azospirillum brasilense FP2 Bacteria in Wheat Roots by Strain-Specific Quantitative PCR.

    Science.gov (United States)

    Stets, Maria Isabel; Alqueres, Sylvia Maria Campbell; Souza, Emanuel Maltempi; Pedrosa, Fábio de Oliveira; Schmid, Michael; Hartmann, Anton; Cruz, Leonardo Magalhães

    2015-10-01

    Azospirillum is a rhizobacterial genus containing plant growth-promoting species associated with different crops worldwide. Azospirillum brasilense strains exhibit a growth-promoting effect by means of phytohormone production and possibly by N2 fixation. However, one of the most important factors for achieving an increase in crop yield by plant growth-promoting rhizobacteria is the survival of the inoculant in the rhizosphere, which is not always achieved. The objective of this study was to develop quantitative PCR protocols for the strain-specific quantification of A. brasilense FP2. A novel approach was applied to identify strain-specific DNA sequences based on a comparison of the genomic sequences within the same species. The draft genome sequences of A. brasilense FP2 and Sp245 were aligned, and FP2-specific regions were filtered and checked for other possible matches in public databases. Strain-specific regions were then selected to design and evaluate strain-specific primer pairs. The primer pairs AzoR2.1, AzoR2.2, AzoR5.1, AzoR5.2, and AzoR5.3 were specific for the A. brasilense FP2 strain. These primer pairs were used to monitor quantitatively the population of A. brasilense in wheat roots under sterile and nonsterile growth conditions. In addition, coinoculations with other plant growth-promoting bacteria in wheat were performed under nonsterile conditions. The results showed that A. brasilense FP2 inoculated into wheat roots is highly competitive and achieves high cell numbers (∼10(7) CFU/g [fresh weight] of root) in the rhizosphere even under nonsterile conditions and when coinoculated with other rhizobacteria, maintaining the population at rather stable levels for at least up to 13 days after inoculation. The strategy used here can be applied to other organisms whose genome sequences are available. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Activated prostaglandin D2 receptors on macrophages enhance neutrophil recruitment into the lung

    Science.gov (United States)

    Jandl, Katharina; Stacher, Elvira; Bálint, Zoltán; Sturm, Eva Maria; Maric, Jovana; Peinhaupt, Miriam; Luschnig, Petra; Aringer, Ida; Fauland, Alexander; Konya, Viktoria; Dahlen, Sven-Erik; Wheelock, Craig E.; Kratky, Dagmar; Olschewski, Andrea; Marsche, Gunther; Schuligoi, Rufina; Heinemann, Akos

    2016-01-01

    Background Prostaglandin (PG) D2 is an early-phase mediator in inflammation, but its action and the roles of the 2 D-type prostanoid receptors (DPs) DP1 and DP2 (also called chemoattractant receptor–homologous molecule expressed on TH2 cells) in regulating macrophages have not been elucidated to date. Objective We investigated the role of PGD2 receptors on primary human macrophages, as well as primary murine lung macrophages, and their ability to influence neutrophil action in vitro and in vivo. Methods In vitro studies, including migration, Ca2+ flux, and cytokine secretion, were conducted with primary human monocyte-derived macrophages and neutrophils and freshly isolated murine alveolar and pulmonary interstitial macrophages. In vivo pulmonary inflammation was assessed in male BALB/c mice. Results Activation of DP1, DP2, or both receptors on human macrophages induced strong intracellular Ca2+ flux, cytokine release, and migration of macrophages. In a murine model of LPS-induced pulmonary inflammation, activation of each PGD2 receptor resulted in aggravated airway neutrophilia, tissue myeloperoxidase activity, cytokine contents, and decreased lung compliance. Selective depletion of alveolar macrophages abolished the PGD2-enhanced inflammatory response. Activation of PGD2 receptors on human macrophages enhanced the migratory capacity and prolonged the survival of neutrophils in vitro. In human lung tissue specimens both DP1 and DP2 receptors were located on alveolar macrophages along with hematopoietic PGD synthase, the rate-limiting enzyme of PGD2 synthesis. Conclusion For the first time, our results show that PGD2 markedly augments disease activity through its ability to enhance the proinflammatory actions of macrophages and subsequent neutrophil activation. PMID:26792210

  17. A short life history of Prof. Dr. F.P. Jonker

    NARCIS (Netherlands)

    Janssen, C.R.

    1978-01-01

    This year Prof. Dr. F.P. Jonker, Frits as he is known among his friends, will retire from the formal academic life at the State University of Utrecht: a long and busy life of 49 years, devoted to teaching, administration, and scientific research. Looking back on all these years, one realises the

  18. [Development of a Striatal and Skull Phantom for Quantitative 123I-FP-CIT SPECT].

    Science.gov (United States)

    Ishiguro, Masanobu; Uno, Masaki; Miyazaki, Takuma; Kataoka, Yumi; Toyama, Hiroshi; Ichihara, Takashi

    123 Iodine-labelled N-(3-fluoropropyl) -2β-carbomethoxy-3β-(4-iodophenyl) nortropane ( 123 I-FP-CIT) single photon emission computerized tomography (SPECT) images are used for differential diagnosis such as Parkinson's disease (PD). Specific binding ratio (SBR) is affected by scattering and attenuation in SPECT imaging, because gender and age lead to changes in skull density. It is necessary to clarify and correct the influence of the phantom simulating the the skull. The purpose of this study was to develop phantoms that can evaluate scattering and attenuation correction. Skull phantoms were prepared based on the measuring the results of the average computed tomography (CT) value, average skull thickness of 12 males and 16 females. 123 I-FP-CIT SPECT imaging of striatal phantom was performed with these skull phantoms, which reproduced normal and PD. SPECT images, were reconstructed with scattering and attenuation correction. SBR with partial volume effect corrected (SBR act ) and conventional SBR (SBR Bolt ) were measured and compared. The striatum and the skull phantoms along with 123 I-FP-CIT were able to reproduce the normal accumulation and disease state of PD and further those reproduced the influence of skull density on SPECT imaging. The error rate with the true SBR, SBR act was much smaller than SBR Bolt . The effect on SBR could be corrected by scattering and attenuation correction even if the skull density changes with 123 I-FP-CIT on SPECT imaging. The combination of triple energy window method and CT-attenuation correction method would be the best correction method for SBR act .

  19. Practical benefit of [123I[FP-CIT SPET in the demonstration of the dopaminergic deficit in Parkinson's disease

    International Nuclear Information System (INIS)

    Booij, J.; Tissingh, G.; Winogrodzka, A.; Boer, G.J.; Wolters, E.C.; Royen, E.A. van

    1997-01-01

    Loss of striatal dopamine (DA) transporters in Parkinson's disease (PD) has been accurately assessed in vivo by single-photon emission tomography (SPET) studies using [ 123 I[β-CIT. However, these studies have also shown that adequate imaging of the striatal DA transporter content can be performed only 20-30 h following the injection of [ 123 I[β-CIT, which is not convenient for routine out-patient evaluations. Recently, a new ligand, N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)tropane (FP-CIT), became available for in vivo imaging of the DA transporter. The faster kinetics of [ 123 I[FP-CIT have been shown to allow adequate acquisition as early as 3 h following injection. In the present study, loss of striatal DA transporters in five non-medicated PD patients was assessed on two consecutive SPET scans, one with [ 123 I[β-CIT (24 h following injection) and one with [ 123 I[FP-CIT (3 h following injection). The ratios of specific to non-specific [ 123 I[FP-CIT uptake in the caudate nucleus and putamen were consistently 2.5-fold lower than those of [ 123 I[β-CIT. However, when the uptake ratio of both ligands in these brain regions of patients was expressed as a percentage of the uptake ratio found in healthy controls, both the decrease and the variation of the data were similar. It is concluded on the basis of these findings that [ 123 I[FP-CIT seems as good as [ 123 I[β-CIT for the assessment of the dopaminergic deficit in PD. The faster kinetics of [ 123 I[FP-CIT are a clear advantage. (orig.). With 3 figs

  20. Differential diagnosis of Parkinsonism using dual phase F 18 FP CIT PET imaging

    International Nuclear Information System (INIS)

    Jin, So Young; Oh, Min Young; Ok, Seung Jun; Oh, Jung Su; Lee, Sang Ju; Chung, Sun Ju; Lee, Chong Sik; Kim, Jae Seung

    2012-01-01

    Dopamine transporter (DAT) imaging can demonstrate presynaptic dopaminergic neuronal loss in Parkinson's disease (PD). However, differentiating atypical parkinsonism (APD) from PD is often difficult. We investigated the usefulness of dual phase F 18 FP CIT positron emission tomography (PET) imaging in the differential diagnosis of parkinsonism. Ninety eight subjects [five normal, seven drug induced parkinsonism (DIP), five essential tremor (ET), 24 PD, 20 multiple system atrophy parkinson type (MSA-P), 13 multiple system atrophy cerebellar type (MSA-C), 13 progressive supranuclear palsy (PSP), and 11 dementia with Lewy bodies(DLB)] underwent F 18 FP CIT PET. PET images were acquired at 5 min (early phase) and 3 h (late phase) after F 18 FP CIT administration (185MBq). Regional uptake pattern of cerebral and cerebellar hemispheres was assessed on early phase images, using visual, quantitative, and statistical parametric mapping (SPM) analyses. Striatal DAT binding was normal in normal, ET, DIP, and MSA C groups, but abnormal in PD, MSA P PSP, and DLB groups. No difference was found in regional uptake on early phase images among normal DAT binding groups, except in the MSA C group. Abnormal DAT binding groups showed different regional uptake pattern on early phase images compared with PD in SPM analysis (FDR<0.05). When discriminating APD from PD, visual interpretation of the early phase image showed high diagnostic sensitivity and specificity (75.4% and 100%, respectively). Regarding the ability to distinguish specific APD, sensitivities were 81% for MSA P, 77% for MSA C, 23% for PSP, and 54.5% for DLB. Dual phase F 18 FP CIT PET imaging is useful in demonstrating striatal DAT loss in neurodegenerative parkinsonism, and also in differentiating APD, particularly MSA, from PD

  1. Differential diagnosis of Parkinsonism using dual phase F 18 FP CIT PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Jin, So Young; Oh, Min Young; Ok, Seung Jun; Oh, Jung Su; Lee, Sang Ju; Chung, Sun Ju; Lee, Chong Sik; Kim, Jae Seung [Univ. of Ulsan, Seoul (Korea, Republic of)

    2012-03-15

    Dopamine transporter (DAT) imaging can demonstrate presynaptic dopaminergic neuronal loss in Parkinson's disease (PD). However, differentiating atypical parkinsonism (APD) from PD is often difficult. We investigated the usefulness of dual phase F 18 FP CIT positron emission tomography (PET) imaging in the differential diagnosis of parkinsonism. Ninety eight subjects [five normal, seven drug induced parkinsonism (DIP), five essential tremor (ET), 24 PD, 20 multiple system atrophy parkinson type (MSA-P), 13 multiple system atrophy cerebellar type (MSA-C), 13 progressive supranuclear palsy (PSP), and 11 dementia with Lewy bodies(DLB)] underwent F 18 FP CIT PET. PET images were acquired at 5 min (early phase) and 3 h (late phase) after F 18 FP CIT administration (185MBq). Regional uptake pattern of cerebral and cerebellar hemispheres was assessed on early phase images, using visual, quantitative, and statistical parametric mapping (SPM) analyses. Striatal DAT binding was normal in normal, ET, DIP, and MSA C groups, but abnormal in PD, MSA P PSP, and DLB groups. No difference was found in regional uptake on early phase images among normal DAT binding groups, except in the MSA C group. Abnormal DAT binding groups showed different regional uptake pattern on early phase images compared with PD in SPM analysis (FDR<0.05). When discriminating APD from PD, visual interpretation of the early phase image showed high diagnostic sensitivity and specificity (75.4% and 100%, respectively). Regarding the ability to distinguish specific APD, sensitivities were 81% for MSA P, 77% for MSA C, 23% for PSP, and 54.5% for DLB. Dual phase F 18 FP CIT PET imaging is useful in demonstrating striatal DAT loss in neurodegenerative parkinsonism, and also in differentiating APD, particularly MSA, from PD.

  2. High spin structure of {sup 35}Cl and the sd-fp shell gap

    Energy Technology Data Exchange (ETDEWEB)

    Kshetri, Ritesh [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Saha Sarkar, M. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India)]. E-mail: maitrayee.sahasarkar@saha.ac.in; Ray, Indrani [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Banerjee, P. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Sarkar, S. [Department of Physics, Bengal Engineering and Science University, Shibpur, Howrah 711103 (India); Raut, Rajarshi [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Goswami, A. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Chatterjee, J.M. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Chattopadhyay, S. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Datta Pramanik, U. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Mukherjee, A. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Dey, C.C. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Bhattacharya, S. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Dasmahapatra, B. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Bhowal, Samit [Department of Physics, Surendranath Evening College, Kolkata 700009 (India); Gangopadhyay, G. [University of Calcutta, 92, Acharya Prafulla Chandra Road, Kolkata 700009 (India); Datta, P. [Anandamohan College, 102/1, Raja Rammohan Sarani, Kolkata 700009 (India); Jain, H.C. [Tata Institute of Fundamental Research, Mumbai 400005 (India); Bhowmik, R.K. [Inter-University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi 110067 (India); Muralithar, S.; Singh, R.P.; Kumar, R. [Inter-University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi 110067 (India)

    2007-01-15

    The high spin states of {sup 35}Cl have been studied by in-beam {gamma}-spectroscopy following the fusion-evaporation reaction {sup 12}C({sup 28}Si,{alpha}p){sup 35}Cl at E{sub lab}=70 and 88 MeV, using the Indian National Gamma (Clover) Array (INGA). Lifetimes of six new excited states have been estimated for the first time. To understand the underlying structure of the levels and transition mechanisms, experimental results have been compared with those from the large basis cross-shell shell model calculations. Involvement of orbitals from fp shell and squeezing of the sd-fp shell gap seem to be essential for reliable reproduction of high spin states.

  3. Two-proton radioactivity in proton-rich fp shell nuclei at high spin

    Energy Technology Data Exchange (ETDEWEB)

    Aggarwal, Mamta [Nuclear Science Centre, Aruna Asaf Ali Marg, Post Box 10502, New Delhi 110067 (India)

    2006-07-15

    Two-proton radioactivity in extremely proton-rich fp shell nuclei at high spins is investigated in a theoretical framework. Separation energy and entropy fluctuate with spin and hence affect the location of the proton drip line.

  4. Two-proton radioactivity in proton-rich fp shell nuclei at high spin

    International Nuclear Information System (INIS)

    Aggarwal, Mamta

    2006-01-01

    Two-proton radioactivity in extremely proton-rich fp shell nuclei at high spins is investigated in a theoretical framework. Separation energy and entropy fluctuate with spin and hence affect the location of the proton drip line

  5. Development of advanced instrumentation for the Phebus FP project-preliminary studies

    International Nuclear Information System (INIS)

    Hampel, G.; Poss, G.

    1989-10-01

    The objective of the project was to examine advanced measuring methods for on-line determination of aerosol, thermohydraulic and hydrogen parameters for their usefulness in the French core melting programme PHEBUS FP. Advanced methods that are known from reactor safety programmes as well as novel measuring techniques as used in related fields such as fuel reprocessing and in non-nuclear process technology have been described and analysed with a view to their potential application in the planned tests. Possibly necessary further developments and modifications have been identified and approaches to solution have been outlined. Special emphasis has been put on the present state of radiation resistant optical fibre wave-guides, which might be integrated in several instruments. As regards the particularly important on-line aerosol measurements in PHEBUS FP, a combined system is recommended as the most promising further development. This novel system configuration comprises the mass monitor of a MESA dust monitoring system and one or several photometers of EIR design

  6. Performance of 6FDA–6FpDA polyimide for propylene/propane separations

    KAUST Repository

    Das, Mita; Koros, William J.

    2010-01-01

    This work addresses the challenges faced by previous researchers with 6FDA-6FpDA polyimide for propylene/propane separations due to plasticization. A study of film annealing temperature is reported to optimize plasticization suppression in elevated

  7. Synthesis and labelling of 125/131I-FP-β-CIT as a dopamine transporter imaging agent

    International Nuclear Information System (INIS)

    Fang Ping; Chen Zhengping; Zhou Xiang

    2002-01-01

    The ligand of N-(3-fluoro propyl)-2β-carbomethoxy-3β-(4'-iodo phenyl) nortropane (FP-β-CIT) and its tributylstannyl precursor were synthesized by hydrolysis of cocaine, and then dehydration, esterification, Grignard reaction, n-demethylation, iodination, n-alkylation and tributylstannylation. 125/131 I-FP-β-CIT were prepared by oxidation radioiododestannylation, using peroxy acetic acid as oxidant, of its tributylstannyl precursor. The stable labelled compound was synthesized with high radiochemical purity at pH 4-7

  8. A flexible testing facility for high-power targets (Tiara FP7 program)

    CERN Document Server

    Fusco, Y.; Samec, K.; Kadi, Y.

    2014-01-01

    Building on recent experience in the field of applied physics, TIARA Work package n° 9 focuses on target applications for accelerators in Europe. A roadmap for target development has been derived from major achievements in the EU-FP6 and EU-FP7 programs such as the MEGAPIE and EURISOL experiments. The TIARA management board concluded that a worthwhile continuation of such projects would be in the development of a flexible material irradiation facility easily transportable and which could be installed in different laboratories. The power is limited to 100 kW in a very compact arrangement so as to obtain the best neutron economy from a moderate beam power which is more likely to be found in laboratories across Europe. The challenges posed by such a compact design and accompanying calculations are presented in the current work.

  9. Evaluating the Latent Structure of the MMPI-2 F(p) Scale in a Forensic Sample: A Taxometric Analysis

    Science.gov (United States)

    Strong, David R.; Glassmire, David M.; Frederick, Richard I.; Greene, Roger L.

    2006-01-01

    P. A. Arbisi and Y. S. Ben-Porath (1995) originally proposed that the Infrequency Psychopathology scale, F(p), be used as the final step in an algorithm to determine the validity of a Minnesota Multiphasic Personality Inventory-2 (MMPI-2) protocol. The current study used taxometric procedures to determine the latent structure of F(p) among…

  10. Use of finger-prick dried blood spots (fpDBS) and capillary electrophoresis for carbohydrate deficient transferrin (CDT) screening in forensic toxicology.

    Science.gov (United States)

    Bertaso, Anna; Sorio, Daniela; Vandoros, Anthula; De Palo, Elio F; Bortolotti, Federica; Tagliaro, Franco

    2016-10-01

    Continued progress in chronic alcohol abuse investigation requires the development of less invasive procedures for screening purposes. The application of finger-prick and related dried blood spots (fpDBS) for carbohydrate deficient transferrin (CDT) detection appears suitable for this aim. Therefore, the goal of this project was to develop a screening method for CDT using fpDBS with CZE analysis. Blood samples prepared by finger-prick were placed on DBS cards and left to air dry; each dried fpDBS disc was shredded into small pieces and suspended in acid solution (60 μL of HCl 120 mmol/L). After centrifugation (10 min at 1500 × g), the collected sample was adjusted to pH 3.5. After an overnight incubation, the pH was neutralised and an iron rich solution was added. After 1 h, CZE analysis was carried out. A group of 47 individuals was studied. Parallel serum samples were collected from each investigated subject and the %CDT for each sample was measured using HPLC and CZE techniques. The fpDBS transferrin sialo isoform electropherograms were similar to those obtained with serum. Moreover, fpDBS CZE CDT percentage levels demonstrated significant statistical correlation with those obtained from serum for both HPLC and CZE %CDT (p < 0.01; r 2 = 0.8913 and 0.8976, respectively), with %CDT from 0.8 to 13.7% for fpDBS and from 0.7 to 12.7% for serum. The newly developed fpDBS procedure for CDT analysis provides a simple and inexpensive tool for use in population screening. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Shell-model results in fp and fpg9/2 spaces for 61,63,65Co isotopes

    International Nuclear Information System (INIS)

    Srivastava, P. C.; Kota, V. K. B.

    2011-01-01

    Low-lying spectra and several high-spin states of odd-even 61,63,65 Co isotopes are calculated in two different shell-model spaces. First set of calculations have been carried out in fp-shell valence space (full fp space for 63,65 Co and a truncated one for 61 Co) using two recently derived fp-shell interactions, namely GXPF1A and KB3G, with 40 Ca as core. Similarly, the second set of calculations have been performed in fpg 9/2 valence space using an fpg effective interaction due to Sorlin et al., with 48 Ca as core and imposing a truncation. It is seen that the results of GXPF1A and KB3G are reasonable for 61,63 Co. For 65 Co, shell-model results show that the fpg interaction adopted in the study is inadequate and also points out that it is necessary to include orbitals higher than 1g 9/2 for neutron-rich Co isotopes.

  12. Equipment-independent reference values for dopamine transporter imaging with 123I-FP-CIT

    International Nuclear Information System (INIS)

    Koch, W.; Hornung, J.; Poepperl, G.; Tatsch, K.; Hamann, C.

    2007-01-01

    Aim: Reliable reference values are helpful to interpret and compare the results of dopamine transporter imaging with SPECT. Since semi-quantitative reference values cannot be easily transferred between imaging equipments, this study aimed to establish equipment independent normal values for the true striatal binding of 123 I-FP-CIT. Patients, methods: Specific striatal FP-CIT binding of 6 healthy volunteers and 26 patients with essential tremor were used to generate a reference range by applying an equipment specific resolution dependent factor to compensate for recovery effects. This factor has been determined previously by a series of standardized phantom measurements of an anthropomorphic basal ganglia phantom. Herewith, the resulting DAT binding values represent the expected true specific binding in the striatum. Results: On average, true specific striatal binding was 5.83 ± 0.96 in healthy controls, 5.25 ± 0.67 in patients with essential tremor and 5.36 ± 0.75 in the entire study cohort. Conclusion: These preliminary results may serve as a basis for the generation of a generally accepted equipment independent reference range for dopamine transporter imaging with 123 I-FP-CIT. By a simple phantom measurement that can be accomplished within one day factors related to specific imaging equipment and processing can be corrected for, resulting in specific binding values which may enable a more standardized interpretation of dopamine transporter scans. (orig.)

  13. FP 6 EU - COVERS. Coordination action - VVER safety research

    International Nuclear Information System (INIS)

    Vasa, I.

    2008-01-01

    In this work research program of the European Union FP 6 - COVERS coordinated by the NRI Rez is presented. COVERS is designed to improve professional and communication environment in the specific area covering all aspects of safe and reliable operation of nuclear power plants with VVER-440 and VVER-1000 reactors. Project Consortium is composed of 26 research and development, engineering and technical support organisations of European VVER-operating and other EU and non-EU countries.

  14. Magnetic resonance imaging, percentage of dense cells and serum prostanoids as tools for objective assessment of pain crisis

    International Nuclear Information System (INIS)

    Mankad, V.N.; Williams, J.P.; Harpen, M.; Longenecker, G.; Brogdon, B.; Moore, B.

    1987-01-01

    Magnetic resonance imaging (MRI) has added a new dimension to the identification of soft tissue abnormalities. Chemical and histological characteristics of the tissues can be separated by computerized reconstruction algorithms which produce images and quantitative data. This technique, which is now becoming available in many centers, determines the density of protons of hydrogen in various tissues. If the infarction of the tissues leads to changes in chemical composition of the cells, it may produce changes in the image or in the quantitative data about the resonance of protons. Studies correlating hematologic parameters, radiologic changes in the bones or bone marrow and pain crises are scarce. It is likely that presence of abnormal hemoglobin in the red cell, which produces changes in red cells and rheology of blood, would produce changes in hematological parameters and MRI during pain crisis. The authors, therefore, undertook an evaluation of MRI of bones in sickle cell patients during pain-free and painful periods and obtained measurements of dense sickle cells and prostanoids derived from platelets and endothelium

  15. Machine learning models for the differential diagnosis of vascular parkinsonism and Parkinson's disease using [123I]FP-CIT SPECT

    International Nuclear Information System (INIS)

    Huertas-Fernandez, I.; Benitez-Rivero, S.; Jesus, S.; Caceres-Redondo, M.T.; Martin-Rodriguez, J.F.; Carrillo, F.; Garcia-Gomez, F.J.; Marin-Oyaga, V.A.; Lojo, J.A.; Garcia-Solis, D.; Mir, P.

    2015-01-01

    The study's objective was to develop diagnostic predictive models using data from two commonly used [ 123 I]FP-CIT SPECT assessment methods: region-of-interest (ROI) analysis and whole-brain voxel-based analysis. We included retrospectively 80 patients with vascular parkinsonism (VP) and 164 patients with Parkinson's disease (PD) who underwent [ 123 I]FP-CIT SPECT. Nuclear-medicine specialists evaluated the scans and calculated bilateral caudate and putamen [ 123 I]FP-CIT uptake and asymmetry indices using BRASS software. Statistical parametric mapping (SPM) was used to compare the radioligand uptake between the two diseases at the voxel level. Quantitative data from these two methods, together with potential confounding factors for dopamine transporter availability (sex, age, disease duration and severity), were used to build predictive models following a tenfold cross-validation scheme. The performance of logistic regression (LR), linear discriminant analysis and support vector machine (SVM) algorithms for ROI data, and their penalized versions for SPM data (penalized LR, penalized discriminant analysis and SVM), were assessed. Significant differences were found in the ROI analysis after covariate correction between VP and PD patients in [ 123 I]FP-CIT uptake in the more affected side of the putamen and the ipsilateral caudate. Age, disease duration and severity were also found to be informative in feeding the statistical model. SPM localized significant reductions in [ 123 I]FP-CIT uptake in PD with respect to VP in two specular clusters comprising areas corresponding to the left and right striatum. The diagnostic predictive accuracy of the LR model using ROI data was 90.3 % and of the SVM model using SPM data was 90.4 %. The predictive models built with ROI data and SPM data from [ 123 I]FP-CIT SPECT provide great discrimination accuracy between VP and PD. External validation of these methods is necessary to confirm their applicability across centres. (orig.)

  16. Clinical features and {sup 123}I-FP-CIT SPECT imaging in drug-induced parkinsonism and Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Corrales, Francisco J.; Escobar-Delgado, Teresa [Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia, Instituto de Biomedicina de Sevilla, Seville (Spain); Sanz-Viedma, Salome [Hospital Universitario Virgen del Rocio, Unidad Diagnostica de Medicina Nuclear, Seville (Spain); Garcia-Solis, David [Hospital Universitario Virgen del Rocio, Unidad Diagnostica de Medicina Nuclear, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain); Mir, Pablo [Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia, Instituto de Biomedicina de Sevilla, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain); Hospital Universitario Virgen del Rocio, Unidad de Trastornos del Movimiento. Servicio de Neurologia, Seville (Spain)

    2010-03-15

    To determine clinical predictors and accuracy of {sup 123}I-FP-CIT SPECT imaging in the differentiation of drug-induced parkinsonism (DIP) and Parkinson's disease (PD). Several clinical features and {sup 123}I-FP-CIT SPECT images in 32 patients with DIP, 25 patients with PD unmasked by antidopaminergic drugs (PDu) and 22 patients with PD without a previous history of antidopaminergic treatment (PDc) were retrospectively evaluated. DIP and PD shared all clinical features except symmetry of parkinsonian signs which was more frequently observed in patients with DIP (46.9%) than in patients with PDu (16.0%, p<0.05) or PDc (4.5%, p<0.01). Qualitatively {sup 123}I-FP-CIT SPECT images were normal in 29 patients with DIP (90.6%) and abnormal in all patients with PD, and this imaging technique showed high levels of accuracy. DIP and PD are difficult to differentiate based on clinical signs. The precision of clinical diagnosis could be reliably enhanced by {sup 123}I-FP-CIT SPECT imaging. (orig.)

  17. Increased brain temserotoneric transporter availability in adult migraineurs: ([18F]FP-CIT PET imaging pilot study

    International Nuclear Information System (INIS)

    Park, Eun Kyung; Hwang, Yu Mi; Chu, Min Kyung; Jung, Ki Young

    2016-01-01

    Recent studies have proposed central serotonergic dysfunction as a major pathophysiology of migraine. We investigated serotonin transporter (SERT) availability in migraineurs using F-18-N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([18F]FP-CIT) positron emission tomography (PET). Brain [18F]FP-CIT PET images were obtained in eight women with migraine during headache free phase and 12 healthy adult women, 120 min after injection of 185 MBq. Non-displaceable binding potential (BP ND) of [18F]FP-CIT, which is an estimate of SERT availability, was calculated at the brainstem and compared with clinical parameters. BP ND at the brainstem was significantly higher in adult migraineurs (n = 6, 1.15 ± 0.17) than healthy subjects (0.95 ± 0.14) (p = 0.04). Healthy subjects demonstrated negative correlation between brainstem BP ND and age (r = −0.64, p = 0.02), whereas this age-related decline pattern was not found in the migraineurs. Severity of migraine attack was significantly correlated with brainstem BP ND (r = 0.66, p = 0.02), when age and duration of illness were corrected. Increased SERT availability in the brainstem of adult migraineurs indicates low serotonin neurotransmission during headache-free phase. Patients who experience more painful headaches have lower serotonin neurotransmission. [18F]FP-CIT PET is a useful in vivo imaging technique for evaluating brainstem SERT availability in migraineurs

  18. Increased brain temserotoneric transporter availability in adult migraineurs: ([18F]FP-CIT PET imaging pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun Kyung [Dept. of Nuclear Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul (Korea, Republic of); Hwang, Yu Mi [Center for Research Information, Korea University, Seoul (Korea, Republic of); Chu, Min Kyung [Dept. of Neurology, Sacred Heart Hospital, Hallym University College of Medicine, Anyang (Korea, Republic of); Jung, Ki Young [Dept. of Neurology, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2016-03-15

    Recent studies have proposed central serotonergic dysfunction as a major pathophysiology of migraine. We investigated serotonin transporter (SERT) availability in migraineurs using F-18-N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([18F]FP-CIT) positron emission tomography (PET). Brain [18F]FP-CIT PET images were obtained in eight women with migraine during headache free phase and 12 healthy adult women, 120 min after injection of 185 MBq. Non-displaceable binding potential (BP ND) of [18F]FP-CIT, which is an estimate of SERT availability, was calculated at the brainstem and compared with clinical parameters. BP ND at the brainstem was significantly higher in adult migraineurs (n = 6, 1.15 ± 0.17) than healthy subjects (0.95 ± 0.14) (p = 0.04). Healthy subjects demonstrated negative correlation between brainstem BP ND and age (r = −0.64, p = 0.02), whereas this age-related decline pattern was not found in the migraineurs. Severity of migraine attack was significantly correlated with brainstem BP ND (r = 0.66, p = 0.02), when age and duration of illness were corrected. Increased SERT availability in the brainstem of adult migraineurs indicates low serotonin neurotransmission during headache-free phase. Patients who experience more painful headaches have lower serotonin neurotransmission. [18F]FP-CIT PET is a useful in vivo imaging technique for evaluating brainstem SERT availability in migraineurs.

  19. Clinical studies of 18F-FDG and 18F-FP-β-CIT PET imaging in hemi-Parkinson's disease

    International Nuclear Information System (INIS)

    Zhao Jun; Lin Xiangtong; Guan Yihui; Zuo Chuantao; Zhang Zhengwei; Wang Jian; Sun Bomin; Chen Zhengping

    2003-01-01

    Objective: To study the characteristics of 18 F-fluorodeoxyglucose (FDG) and 18 F-N-3-fluoro-propyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ( 18 F-FP-β-CIT) PET imaging in patients with hemi-Parkinson's disease (hemi-PD) and to assess their value in early diagnosis. Methods: 34 cases of hemi-PD (Hoehn and Yahr stage I-II) and 16 normal control subjects were selected for this study. 16 patients were performed with 18 F-FDG PET imaging, 18 patients with 18 F-FP-β-CIF, while 6 patients of them both 18 F-FDG and 18 F-FP-β-CIT. 30 min after injection of 185-259 MBq 18 F-FDG, 3D brain scans were acquired. Region of interest (ROI) analysis and statistical parametric mapping (SPM) were applied. 18 F-FP-β-CIT PET imaging was carried out 2-3 h post injection, and (ROI-cerebellum)/cerebellum ratio was calculated. Results: In right hemi-PD, reductions in 18 F-FDG metabolism were observed in the left basal ganglia compared with control group, but with no significant difference (P>0.05). The results of SPM analysis showed that a significant reduction in FDG uptake in the left superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus and left middle temporal gyrus, whereas a significant increase in the bilateral precentral gyrus , superior parietal lobule, left middle occipital gyrus and left thalamus as compared with the control group. There was a significant reduction in 18 F-FP-β-CIT uptake in putamen, its reduction was found not only in the contralateral putamen, but also in the ipsilateral ones, and more pronounced in the contralateral posterior putamen. Conclusions: 18 F-FDG PET imaging is non-specific for the early diagnosis of PD. 18 F-FP-β-CIT PET imaging could find the changes of striatum dopamine transporter at early stage, therefore it was helpful for early diagnosis and differential diagnosis of PD. Combined with 18 F-FDG PET imaging, the changes of local cerebral glucose metabolism in PD could also be evaluated

  20. Comparison of the pharmacokinetics of different analogs of 11C-labeled TZTP for imaging muscarinic M2 receptors with PET

    International Nuclear Information System (INIS)

    Reid, Alicia E.; Ding Yushin; Eckelman, William C.; Logan, Jean; Alexoff, David; Shea, Colleen; Xu Youwen; Fowler, Joanna S.

    2008-01-01

    Introduction: The only radiotracer available for the selective imaging of muscarinic M2 receptors in vivo is 3-(3-{3-[ 18 F]fluoropropyl)thio}-1,2,5-thiadiazol-4-yl) -1,2,5,6-tetrahydro-1-methylpyridine) ([ 18 F]FP-TZTP). We have prepared and labeled 3-(3-(3-fluoropropylthio)-1,2,5-thiadiazol-4-yl) -1,2,5,6-tetrahydro-1-methylpyridne (FP-TZTP, 3) and two other TZTP derivatives with 11 C at the methylpyridine moiety to explore the potential of using 11 C-labeled FP-TZTP for positron emission tomography imaging of M2 receptors and to compare the effect of small structural changes on tracer pharmacokinetics (PK) in brain and peripheral organs. Methods: 11 C-radiolabeled FP-TZTP, 3-(3-propylthio)-TZTP (6) and 3,3,3-(3-(3-trifluoropropyl)-TZTP (10) were prepared, and log D, plasma protein binding (PPB), affinity constants, time-activity curves (TACs), area under the curve (AUC) for arterial plasma, distribution volumes (DV) and pharmacological blockade in baboons were compared. Results: Values for log D, PPB and affinity constants were similar for 3, 6 and 10. The fraction of parent radiotracer in the plasma was higher and the AUC lower for 10 than for 3 and 6. TACs for brain regions were similar for 3 and 6, which showed PK similar to the 18 F tracer, while 10 showed slower uptake and little clearance over 90 min. DVs for 3 and 6 were similar to the 18 F tracer but higher for 10. Uptake of the three tracers was significantly reduced by coinjection of unlabeled 3 and 6. Conclusion: Small structural variations on the TZTP structure greatly altered the PK in brain and behavior in blood with little change in the log D, PPB or affinity. The study suggests that 11 C-radiolabeled 3 will be a suitable alternative to [ 18 F]FP-TZTP for translational studies in humans

  1. Synthesis of [18F]-N-3-fluoro-propyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([18F]-FP-β-CIT)

    International Nuclear Information System (INIS)

    Fang Ping; Chen Zhengping; Lin Yansong; Zhou Xian; Du Yikui

    2001-01-01

    The ligand of N-(3-fluoro-propyl)-2β-carbomethoxy-3β-(4'-iodophenyl) nortropane (FP-β-CIT) and mesylate precursor were synthesized by hydrolysis of cocaine, followed by dehydration, esterification, Grignard reaction, N-demethylation, iodination, N-alkylation with 3-bromo-propanol and methyl-sulfonyl. Finally, 18 F-FP-β-CIT was prepared by nucleophilic fluorination of the mesylate with K 18 F/K 2.2.2 (Kryptofix). The labelling yield of 18 F-FP-β-CIT is 25%-30%. The total radiochemical yield of this compound, calculated from the end of bombardment (EOB) with decay correction, is 10%-12% with a synthesis time of 100-110 min. The radiochemical purity of 18 F-FP-β-CIT is greater than 90%, and this compound in aqueous solution is also stable for more than 4 hours at room temperature. It is stable enough for clinical study

  2. Fuzzy-PI-based centralised control of semi-isolated FP-SEPIC/ZETA BDC in a PV/battery hybrid system

    Science.gov (United States)

    Mahendran, Venmathi; Ramabadran, Ramaprabha

    2016-11-01

    Multiport converters with centralised controller have been most commonly used in stand-alone photovoltaic (PV)/battery hybrid system to supply the load smoothly without any disturbances. This study presents the performance analysis of four-port SEPIC/ZETA bidirectional converter (FP-SEPIC/ZETA BDC) using various types of centralised control schemes like Fuzzy tuned proportional integral controller (Fuzzy-PI), fuzzy logic controller (FLC) and conventional proportional integral (PI) controller. The proposed FP-SEPIC/ZETA BDC with various control strategy is derived for simultaneous power management of a PV source using distributed maximum power point tracking (DMPPT) algorithm, a rechargeable battery, and a load by means of centralised controller. The steady state and the dynamic response of the FP-SEPIC/ZETA BDC are analysed using three different types of controllers under line and load regulation. The Fuzzy-PI-based control scheme improves the dynamic response of the system when compared with the FLC and the conventional PI controller. The power balance between the ports is achieved by pseudorandom carrier modulation scheme. The response of the FP-SEPIC/ZETA BDC is also validated experimentally using hardware prototype model of 500 W system. The effectiveness of the control strategy is validated using simulation and experimental results.

  3. Heterotypic contact reveals a COX-2-mediated suppression of osteoblast differentiation by endothelial cells: A negative modulatory role for prostanoids in VEGF-mediated cell: cell communication?

    International Nuclear Information System (INIS)

    Clarkin, Claire E.; Garonna, Elena; Pitsillides, Andrew A.; Wheeler-Jones, Caroline P.D.

    2008-01-01

    In bone, angiogenesis must be initiated appropriately, but limited once remodelling or repair is complete. Our recent findings have supported a role for prostaglandins (PG), known modulators of osteoblast (OB) and endothelial cell (EC) behaviour, in facilitating VEGF-mediated paracrine communication from OBs to 'remotely located' ECs, but the mechanism(s) regulating OB:EC crosstalk when these cells are closely opposed are undefined. In this study we have examined: (i) the effects of exogenous PGE 2 on VEGF-driven events in ECs, and (ii) the role of endogenous COX-2-derived prostanoids in mediating communication between intimately opposed OBs and ECs in direct contact. Exposure of ECs to PGE 2 increased ERK1/2 phosphorylation, COX-2 induction, 6-keto-PGF 1α release and EC proliferation. In contrast, PGE 2 attenuated VEGF 165 -induced VEGFR2/Flk1 phosphorylation, ERK1/2 activation and proliferation of ECs, suggesting that exogenous PGE 2 restricts the actions of VEGF. However, the COX-2-selective inhibitor, NS398, also attenuated VEGF-induced proliferation, implying a distinct role for endogenous COX-2 activity in regulating EC behaviour. To examine the effect of OB:EC proximity and the role of COX-2 products further, we used a confrontational co-culture model. These studies showed that COX-2 blockade with NS398 enhanced EC-dependent increases in OB differentiation, that this effect was reversed by exogenous PGH 2 (immediate COX-2 product), and that exogenous VEGF did not influence EC-dependent OB differentiation under these conditions. Our findings indicate that locally produced prostanoids may serve distinct roles depending on OB:EC proximity and negatively modulate VEGF-mediated changes in EC behaviour when these cells are closely opposed to control angiogenesis during bone (re)modelling

  4. Comparison of the pharmacokinetics of different analogs of {sup 11}C-labeled TZTP for imaging muscarinic M2 receptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    Reid, Alicia E. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)], E-mail: areid@bnl.gov; Ding Yushin [Radiology Department, Yale University School of Medicine, New Haven, CT 06510 (United States); Eckelman, William C. [Molecular Tracer LLC, Bethesda, MD 20892 (United States); Logan, Jean; Alexoff, David; Shea, Colleen; Xu Youwen; Fowler, Joanna S. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)

    2008-04-15

    Introduction: The only radiotracer available for the selective imaging of muscarinic M2 receptors in vivo is 3-(3-{l_brace}3-[{sup 18}F]fluoropropyl)thio{r_brace}-1,2,5-thiadiazol-4-yl) -1,2,5,6-tetrahydro-1-methylpyridine) ([{sup 18}F]FP-TZTP). We have prepared and labeled 3-(3-(3-fluoropropylthio)-1,2,5-thiadiazol-4-yl) -1,2,5,6-tetrahydro-1-methylpyridne (FP-TZTP, 3) and two other TZTP derivatives with {sup 11}C at the methylpyridine moiety to explore the potential of using {sup 11}C-labeled FP-TZTP for positron emission tomography imaging of M2 receptors and to compare the effect of small structural changes on tracer pharmacokinetics (PK) in brain and peripheral organs. Methods: {sup 11}C-radiolabeled FP-TZTP, 3-(3-propylthio)-TZTP (6) and 3,3,3-(3-(3-trifluoropropyl)-TZTP (10) were prepared, and log D, plasma protein binding (PPB), affinity constants, time-activity curves (TACs), area under the curve (AUC) for arterial plasma, distribution volumes (DV) and pharmacological blockade in baboons were compared. Results: Values for log D, PPB and affinity constants were similar for 3, 6 and 10. The fraction of parent radiotracer in the plasma was higher and the AUC lower for 10 than for 3 and 6. TACs for brain regions were similar for 3 and 6, which showed PK similar to the {sup 18}F tracer, while 10 showed slower uptake and little clearance over 90 min. DVs for 3 and 6 were similar to the {sup 18}F tracer but higher for 10. Uptake of the three tracers was significantly reduced by coinjection of unlabeled 3 and 6. Conclusion: Small structural variations on the TZTP structure greatly altered the PK in brain and behavior in blood with little change in the log D, PPB or affinity. The study suggests that {sup 11}C-radiolabeled 3 will be a suitable alternative to [{sup 18}F]FP-TZTP for translational studies in humans.

  5. Quantification of Iodine-123-FP-CIT SPECT with a resolution-independent method

    International Nuclear Information System (INIS)

    Dobbeleir, A.A.; Ham, H.R.; Hambye, A.E.; Vervaet, A.M.

    2005-01-01

    Accurate quantification of small-sized objects by SPECT is hampered by the partial volume effect. The present work evaluates the magnitude of this phenomenon with Iodine- 123 in phantom studies, and presents a resolution- independent method to quantify striatal I-123 FP-CIT uptake in patients. At first five syringes with internal diameters varying between 9 and 29mm and an anthropomorphic striatal phantom were filled with known concentrations of Iodine-123 and imaged by SPECT using different collimators and radii of rotation. Data were processed with and without scatter correction. From the measured activities, calibration factors were calculated for each specific collimator. Then a resolution-independent method for FP-CIT quantification using large regions of interest was developed and validated in 34 human studies (controls and patients) acquired in 2 different hospitals, by comparing its results to those obtained by a semi- quantitative striatal-to-occipital analysis. Taking the injected activity and decay into account, the measured counts/volume could be converted into absolute tracer concentrations. For the fan-beam, high resolution and medium energy collimators, the measured maximum activity in comparison to the 29 mm-diameter syringe was respectively 38%, 16% and 9% for the 9 mm-diameter syringe and 82%, 80% and 30% for the 16 mm syringe, and not significantly modified after scatter correction. For the anthropomorphic phantom, the error in measurement in % of the true concentration ranged between 0.3-9.5% and was collimator dependent. Medium energy collimators yielded the most homogeneous results. In the human studies, inter- observer variability was 11.4% for the striatal-to-occipital ratio and 3.1% for the resolution-independent method, with correlation coefficients >0.8 between both. The resolution- independent method was 89%-sensitive and 100%-specific to separate the patients without and with abnormal FP-CIT uptake (accuracy: 94%). Also the

  6. Cloning and sequencing of a cellobiohydrolase gene from Trichoderma harzianum FP108

    Science.gov (United States)

    Patrick Guilfoile; Ron Burns; Zu-Yi Gu; Matt Amundson; Fu-Hsian Chang

    1999-01-01

    A cbbl cellobiohydrolase gene was cloned and sequenced from the fungus Trichoderrna harzianum FP108. The cloning was performed by PCR amplification of T. harzianum genomic DNA, using PCR primers whose sequence was based on the cbbl gene from Tricboderma reesei. The 3' end of the gene was isolated by inverse...

  7. EP3/FP dual receptor agonist ONO-9054 administered morning or evening to patients with open-angle glaucoma or ocular hypertension: results of a randomised crossover study

    Science.gov (United States)

    Berlin, Michael S; Rowe-Rendleman, Cheryl; Ahmed, Ike; Ross, Douglas T; Fujii, Akifumi; Ouchi, Takafumi; Quach, Christine; Wood, Andrew; Ward, Caroline L

    2016-01-01

    Background/aims The novel prostaglandin E (EP) 3 and prostaglandin F (FP) receptor agonist ONO-9054 is effective in lowering intraocular pressure (IOP) in patients with ocular hypertension and open-angle glaucoma when administered once daily. This study compares the effects of morning (AM) versus evening (PM) dosing of ONO-9054 on tolerability and IOP lowering. Methods This was a single-centre, randomised, double-masked, two-sequence, placebo-controlled crossover study in 12 subjects with bilateral primary open-angle glaucoma or ocular hypertension. Two 14-day crossover regimens were separated by a 2-week washout: ONO-9054 (1 drop to each eye) in the morning (07:00) and vehicle in the evening (19:00) and vice versa. IOP was measured multiple times during select days. Ocular examinations also evaluated safety and tolerability. Results Mild ocular hyperaemia, reported by six subjects with PM dosing, was the most frequent adverse event. Mild to moderate dryness was also slightly more frequent after PM dosing. Maximum IOP reduction from baseline occurred on day 2 with decreases from baseline of −7.4 mm Hg (−30.8%) for AM dosing and −9.1 mm Hg, (−38.0%) for PM dosing; after 14 days, mean reduction in IOP was −6.8 mm Hg (−28.6%) for AM dosing and −7.5 mm Hg (−31.0%) for PM dosing. Conclusions PM dosing of ONO-0954 was associated with a slightly increased frequency of mild hyperaemia and mild to moderate dryness. Both dosing schedules provided sustained reduction in IOP. Trial registration number NCT01670266. PMID:26453641

  8. The relationship of biofilm production to biocontrol activity of Burkholderia pyrrocinia FP62

    Science.gov (United States)

    Foliar biocontrol agent (BCA) efficacy is often inconsistent due to poor colonization and survival on plant surfaces. Burkholderia pyrrocinia FP62, a superior leaf colonist and BCA of Botrytis cinerea, forms unsaturated biofilms on plant surfaces. To determine the relationship between biocontrol act...

  9. Positron emission tomography imaging of cardiomyocyte apoptosis with a novel molecule probe [18F]FP-DPAZn2

    Science.gov (United States)

    Sun, Ting; Tang, Ganghua; Tian, Hua; Hu, Kongzhen; Yao, Shaobo; Su, Yifan; Wang, Changqian

    2015-01-01

    Cardiomyocyte apoptosis plays a causal role in the development and progression of heart failure. Currently, there is no effective imaging agent that can be used to detect cardiomyocyte apoptosis in vivo. To target phosphatidylserine (PS) on the surface of the dying cell, we synthesized a novel 18F-labeled Zn2+-dipicolylamine (DPA) analog, [18F]FP-DPAZn2, and evaluated it for noninvasive imaging of cardiomyocyte apoptosis. In vitro, the fluorescence imaging of dansyl-DPAZn2 was suitable for detecting cardiomyocyte apoptosis, which was confirmed by confocal immunofluorescence imaging, terminal dUTP nick-end labeling (TUNEL) assay, and western blot assay. The in vivo biodistribution showed that the uptake ratios of [18F]FP-DPAZn2 in the heart were 4.41±0.29% ID/g at 5 min, 2.40 ± 0.43% ID/g at 30 min, 1.63 ± 0.26% ID/g at 60 min, and 1.43% ± 0.07 ID/g at 120 min post-injection. In vivo, the [18F]FP-DPAZn2 PET images showed more cardiac accumulation of radioactivity 60 min post-injection in acute myocardial infarction (AMI) rats than in normal rats, which was consistent with the findings of a histological analysis of the rat cardiac tissues in vitro. [18F]FP-DPAZn2 PET imaging has the capability for myocardial apoptosis detection, but the method will require improved myocardial uptake for the noninvasive evaluation of cardiomyocyte apoptosis in clinical settings. PMID:26416423

  10. Acute restraint stress induces endothelial dysfunction: role of vasoconstrictor prostanoids and oxidative stress.

    Science.gov (United States)

    Carda, Ana P P; Marchi, Katia C; Rizzi, Elen; Mecawi, André S; Antunes-Rodrigues, José; Padovan, Claudia M; Tirapelli, Carlos R

    2015-01-01

    We hypothesized that acute stress would induce endothelial dysfunction. Male Wistar rats were restrained for 2 h within wire mesh. Functional and biochemical analyses were conducted 24 h after the 2-h period of restraint. Stressed rats showed decreased exploration on the open arms of an elevated-plus maze (EPM) and increased plasma corticosterone concentration. Acute restraint stress did not alter systolic blood pressure, whereas it increased the in vitro contractile response to phenylephrine and serotonin in endothelium-intact rat aortas. NG-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase, NOS, inhibitor) did not alter the contraction induced by phenylephrine in aortic rings from stressed rats. Tiron, indomethacin and SQ29548 reversed the increase in the contractile response to phenylephrine induced by restraint stress. Increased systemic and vascular oxidative stress was evident in stressed rats. Restraint stress decreased plasma and vascular nitrate/nitrite (NOx) concentration and increased aortic expression of inducible (i) NOS, but not endothelial (e) NOS. Reduced expression of cyclooxygenase (COX)-1, but not COX-2, was observed in aortas from stressed rats. Restraint stress increased thromboxane (TX)B(2) (stable TXA(2) metabolite) concentration but did not affect prostaglandin (PG)F2α concentration in the aorta. Restraint reduced superoxide dismutase (SOD) activity, whereas concentrations of hydrogen peroxide (H(2)O(2)) and reduced glutathione (GSH) were not affected. The major new finding of our study is that restraint stress increases vascular contraction by an endothelium-dependent mechanism that involves increased oxidative stress and the generation of COX-derived vasoconstrictor prostanoids. Such stress-induced endothelial dysfunction could predispose to the development of cardiovascular diseases.

  11. Modeling structure of G protein-coupled receptors in huan genome

    KAUST Repository

    Zhang, Yang

    2016-01-26

    G protein-coupled receptors (or GPCRs) are integral transmembrane proteins responsible to various cellular signal transductions. Human GPCR proteins are encoded by 5% of human genes but account for the targets of 40% of the FDA approved drugs. Due to difficulties in crystallization, experimental structure determination remains extremely difficult for human GPCRs, which have been a major barrier in modern structure-based drug discovery. We proposed a new hybrid protocol, GPCR-I-TASSER, to construct GPCR structure models by integrating experimental mutagenesis data with ab initio transmembrane-helix assembly simulations, assisted by the predicted transmembrane-helix interaction networks. The method was tested in recent community-wide GPCRDock experiments and constructed models with a root mean square deviation 1.26 Å for Dopamine-3 and 2.08 Å for Chemokine-4 receptors in the transmembrane domain regions, which were significantly closer to the native than the best templates available in the PDB. GPCR-I-TASSER has been applied to model all 1,026 putative GPCRs in the human genome, where 923 are found to have correct folds based on the confidence score analysis and mutagenesis data comparison. The successfully modeled GPCRs contain many pharmaceutically important families that do not have previously solved structures, including Trace amine, Prostanoids, Releasing hormones, Melanocortins, Vasopressin and Neuropeptide Y receptors. All the human GPCR models have been made publicly available through the GPCR-HGmod database at http://zhanglab.ccmb.med.umich.edu/GPCR-HGmod/ The results demonstrate new progress on genome-wide structure modeling of transmembrane proteins which should bring useful impact on the effort of GPCR-targeted drug discovery.

  12. [O-methyl-{sup 11}C]{beta}-CIT-FP, a potential radioligand for quantitation of the dopamine transporter: Preparation, autoradiography, metabolite studies, and positron emission tomography examinations

    Energy Technology Data Exchange (ETDEWEB)

    Lundkvist, Camilla; Halldin, Christer; Swahn, Carl-Gunnar; Hall, Haakan; Karlsson, Per; Nakashima, Yoshifumi; Wang, Shaoyin; Milius, Richard A.; Neumeyer, John L.; Farde, Lars

    1995-10-01

    {beta}-CIT-FP [N-(3-fluoropropyl)-2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)nortropane] is a cocaine analogue with a high affinity for the dopamine transporter. [O-methyl-{sup 11}C]{beta}-CIT-FP ([{sup 11}C]{beta}-CIT-FP) was prepared byO -alkylation of the free acid with [{sup 11}C]methyl iodide. The total radiochemical yield of [{sup 11}C]{beta}-CIT-FP was 50 to 60% with an overall synthesis time of 30 min. The radiochemical purity was >99%, and the specific radioactivity at time of injection was about 37 GBq/{mu}mol (1000 Ci/mmol). Autoradiographic examination of [{sup 11}C]{beta}-CIT-FP binding in human brain postmortem demonstrated specific binding in the caudate nucleus and putamen. Positron emission tomography (PET) examination of [{sup 11}C]{beta}-CIT-FP in a Cynomolgus monkey demonstrated accumulation in the striatum with a striatum-to-cerebellum ratio of about 8 after 60 min. Equilibrium in the striatum was attained within 70 to 90 min. The radioactivity ratios of thalamus/cerebellum and neocortex/cerebellum were about 2 and 1.5, respectively. In a displacement experiment, radioactivity in the striatum but not in the cerebellum was reduced after injection of {beta}-CIT, indicating that striatal radioactivity following injection of [{sup 11}C]{beta}-CIT-FP is associated with dopamine transporter sites and that the binding is reversible. The fraction of the total radioactivity in plasma representing [{sup 11}C]{beta}-CIT-FP determined by high-performance liquid chromatography (HPLC) was 84% at 15 min and 50% at 95 min. [{sup 11}C]{beta}-CIT-FP should be a useful PET radioligand for the quantitation of dopamine transporters in the human brain in vivo.

  13. No difference in striatal dopamine transporter availability between active smokers, ex-smokers and non-smokers using (123I)FP-CIT (DaTSCAN) and SPECT

    DEFF Research Database (Denmark)

    Thomsen, G; Knudsen, Gitte Moos; Jensen, PS

    2013-01-01

    BACKGROUND: Mesolimbic and nigrostriatal dopaminergic pathways play important roles in both the rewarding and conditioning effects of drugs. The dopamine transporter (DAT) is of central importance in regulating dopaminergic neurotransmission and in particular in activating the striatal D2-like...... receptors. Molecular imaging studies of the relationship between DAT availability/dopamine synthesis capacity and active cigarette smoking have shown conflicting results. Through the collaboration between 13 SPECT centres located in 10 different European countries, a database of FP-CIT-binding in healthy...... controls was established. We used the database to test the hypothesis that striatal DAT availability is changed in active smokers compared to non-smokers and ex-smokers. METHODS: A total of 129 healthy volunteers were included. Subjects were divided into three categories according to past and present...

  14. Comprehensive Binary Interaction Mapping of SH2 Domains via Fluorescence Polarization Reveals Novel Functional Diversification of ErbB Receptors

    Science.gov (United States)

    Ciaccio, Mark F.; Chuu, Chih-pin; Jones, Richard B.

    2012-01-01

    First-generation interaction maps of Src homology 2 (SH2) domains with receptor tyrosine kinase (RTK) phosphosites have previously been generated using protein microarray (PM) technologies. Here, we developed a large-scale fluorescence polarization (FP) methodology that was able to characterize interactions between SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity than was previously achieved with PMs. We used the FP assay to query the interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine binding (PTB) domains. From 358,944 polarization measurements, the affinities for 1,405 unique biological interactions were determined, 83% of which are novel. In contrast to data from previous reports, our analyses suggested that ErbB2 was not more promiscuous than the other ErbB receptors. Our results showed that each receptor displays unique preferences in the affinity and location of recruited SH2 domains that may contribute to differences in downstream signaling potential. ErbB1 was enriched versus the other receptors for recruitment of domains from RAS GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor family member, was predictably enriched for recruitment of domains from phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many novel interactions were also observed with phosphopeptides corresponding to ErbB receptor tyrosines not previously reported to be phosphorylated by mass spectrometry, suggesting the existence of many biologically relevant RTK sites that may be phosphorylated but below the detection threshold of standard mass spectrometry procedures. This

  15. Comprehensive binary interaction mapping of SH2 domains via fluorescence polarization reveals novel functional diversification of ErbB receptors.

    Directory of Open Access Journals (Sweden)

    Ronald J Hause

    Full Text Available First-generation interaction maps of Src homology 2 (SH2 domains with receptor tyrosine kinase (RTK phosphosites have previously been generated using protein microarray (PM technologies. Here, we developed a large-scale fluorescence polarization (FP methodology that was able to characterize interactions between SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity than was previously achieved with PMs. We used the FP assay to query the interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine binding (PTB domains. From 358,944 polarization measurements, the affinities for 1,405 unique biological interactions were determined, 83% of which are novel. In contrast to data from previous reports, our analyses suggested that ErbB2 was not more promiscuous than the other ErbB receptors. Our results showed that each receptor displays unique preferences in the affinity and location of recruited SH2 domains that may contribute to differences in downstream signaling potential. ErbB1 was enriched versus the other receptors for recruitment of domains from RAS GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor family member, was predictably enriched for recruitment of domains from phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many novel interactions were also observed with phosphopeptides corresponding to ErbB receptor tyrosines not previously reported to be phosphorylated by mass spectrometry, suggesting the existence of many biologically relevant RTK sites that may be phosphorylated but below the detection threshold of standard mass spectrometry

  16. Space weather in the EU’s FP7 Space Theme

    Directory of Open Access Journals (Sweden)

    Chiarini Paola

    2013-11-01

    Full Text Available Technological infrastructures in space and on ground provide services on which modern society and economies rely. Space weather related research is funded under the 7th Framework Programme for Research and Innovation (FP7 of the European Union in response to the need of protecting such critical infrastructures from the damage which could be caused by extreme space weather events. The calls for proposals published under the topic “Security of space assets from space weather events” of the FP7 Space Theme aimed to improve forecasts and predictions of disruptive space weather events as well as identify best practices to limit the impacts on space- and ground-based infrastructures and their data provision. Space weather related work was also funded under the topic “Exploitation of space science and exploration data”, which aims to add value to space missions and Earth-based observations by contributing to the effective scientific exploitation of collected data. Since 2007 a total of 20 collaborative projects have been funded, covering a variety of physical phenomena associated with space weather, from ionospheric disturbances and scintillation, to geomagnetically induced currents at Earth’s surface, to coronal mass ejections and solar energetic particles. This article provides an overview of the funded projects, touching upon some results and referring to specific websites for a more exhaustive description of the projects’ outcomes.

  17. ^2H(^18F,p)^19F Study at 6 MeV/u

    Science.gov (United States)

    Kozub, R. L.; Nesaraja, C. D.; Moazen, B. H.; Scott, J. P.; Bardayan, D. W.; Blackmon, J. C.; Gross, C. J.; Shapira, D.; Smith, M. S.; Batchelder, J. C.; Brune, C. R.; Champagne, A. E.; Sahin, L.; Cizewski, J. A.; Thomas, J. S.; Davinson, T.; Woods, P. J.; Greife, U.; Jewett, C.; Livesay, R. J.; Ma, Z.; Parker, P. D.

    2003-04-01

    The degree to which the (p,α) and (p,γ) reactions destroy ^18F at temperatures ˜1-4 x 10^8 K is important for understanding the synthesis of nuclei in nova explosions and for using ^18F as a monitor of nova mechanisms in gamma ray astronomy. The reactions are dominated by low-lying proton resonances near the ^18F+p threshold (E_x=6.411 MeV excitation energy in ^19Ne). To gain further information about these resonances, we have used the inverse ^18F(d,p)^19F neutron transfer reaction at the Holifield Radioactive Ion Beam Facility to selectively populate corresponding mirror states in ^19F. Proton angular distributions were measured for states in ^19F in the excitation energy range 0-9 MeV. Results and implications for the ^18F+p reactions and nuclear structure will be presented. ^1Supported by DOE. ^2ORNL is managed by UT-Battelle, LLC, for the USDOE.

  18. Hybrid wireless-over-fiber transmission system based on multiple injection-locked FP LDs.

    Science.gov (United States)

    Li, Chung-Yi; Lu, Hai-Han; Chu, Chien-An; Ying, Cheng-Ling; Lu, Ting-Chien; Peng, Peng-Chun

    2015-07-27

    A hybrid wireless-over-fiber (WoF) transmission system based on multiple injection-locked Fabry-Perot laser diodes (FP LDs) is proposed and experimentally demonstrated. Unlike the traditional hybrid WoF transmission systems that require multiple distributed feedback (DFB) LDs to support different kinds of services, the proposed system employs multiple injection-locked FP LDs to provide different kinds of applications. Such a hybrid WoF transmission system delivers downstream intensity-modulated 20-GHz microwave (MW)/60-GHz millimeter-wave (MMW)/550-MHz cable television (CATV) signals and upstream phase-remodulated 20-GHz MW signal. Excellent bit error rate (BER), carrier-to-noise ratio (CNR), composite second-order (CSO), and composite triple-beat (CTB) are observed over a 40-km single-mode fiber (SMF) and a 4-m radio frequency (RF) wireless transport. Such a hybrid WoF transmission system has practical applications for fiber-wireless convergence to provide broadband integrated services, including telecommunication, data communication, and CATV services.

  19. Obligatory Role of EP1 Receptors in the Increase in Cerebral Blood Flow Produced by Hypercapnia in the Mice.

    Directory of Open Access Journals (Sweden)

    Ken Uekawa

    Full Text Available Hypercapnia induces potent vasodilation in the cerebral circulation. Although it has long been known that prostanoids participate in the cerebrovascular effects of hypercapnia, the role of prostaglandin E2 (PGE2 and PGE2 receptors have not been fully investigated. In this study, we sought to determine whether cyclooxygenase-1 (COX-1-derived PGE2 and EP1 receptors are involved in the cerebrovascular response induced by hypercapnia. Cerebral blood flow (CBF was recorded by laser-Doppler flowmetry in the somatosenasory cortex of anesthetized male EP1-/- mice and wild type (WT littermates. In WT mice, neocortical application of the EP1 receptor antagonist SC-51089 attenuated the increase in CBF elicited by systemic hypercapnia (pCO2 = 50-60 mmHg. SC-51089 also attenuated the increase in CBF produced by neocortical treatment of arachidonic acid or PGE2. These CBF responses were also attenuated in EP1-/- mice. In WT mice, the COX-1 inhibitor SC-560, but not the COX-2 inhibitor NS-398, attenuated the hypercapnic CBF increase. Neocortical application of exogenous PGE2 restored the attenuation in resting CBF and the hypercapnic response induced by SC-560. In contrast, exogenous PGE2 failed to rescue the attenuation both in WT mice induced by SC-51089 and EP1-/- mice, attesting to the obligatory role of EP1 receptors in the response. These findings indicate that the hypercapnic vasodilatation depends on COX-1-derived PGE2 acting on EP1 receptors and highlight the critical role that COX-1-derived PGE2 and EP1 receptors play in the hypercapnic regulation of the cerebral circulation.

  20. File Specification for GEOS-5 FP-IT (Forward Processing for Instrument Teams)

    Science.gov (United States)

    Lucchesi, R.

    2013-01-01

    The GEOS-5 FP-IT Atmospheric Data Assimilation System (GEOS-5 ADAS) uses an analysis developed jointly with NOAA's National Centers for Environmental Prediction (NCEP), which allows the Global Modeling and Assimilation Office (GMAO) to take advantage of the developments at NCEP and the Joint Center for Satellite Data Assimilation (JCSDA). The GEOS-5 AGCM uses the finite-volume dynamics (Lin, 2004) integrated with various physics packages (e.g, Bacmeister et al., 2006), under the Earth System Modeling Framework (ESMF) including the Catchment Land Surface Model (CLSM) (e.g., Koster et al., 2000). The GSI analysis is a three-dimensional variational (3DVar) analysis applied in grid-point space to facilitate the implementation of anisotropic, inhomogeneous covariances (e.g., Wu et al., 2002; Derber et al., 2003). The GSI implementation for GEOS-5 FP-IT incorporates a set of recursive filters that produce approximately Gaussian smoothing kernels and isotropic correlation functions. The GEOS-5 ADAS is documented in Rienecker et al. (2008). More recent updates to the model are presented in Molod et al. (2011). The GEOS-5 system actively assimilates roughly 2 × 10(exp 6) observations for each analysis, including about 7.5 × 10(exp 5) AIRS radiance data. The input stream is roughly twice this volume, but because of the large volume, the data are thinned commensurate with the analysis grid to reduce the computational burden. Data are also rejected from the analysis through quality control procedures designed to detect, for example, the presence of cloud. To minimize the spurious periodic perturbations of the analysis, GEOS-5 FP-IT uses the Incremental Analysis Update (IAU) technique developed by Bloom et al. (1996). More details of this procedure are given in Appendix A. The analysis is performed at a horizontal resolution of 0.625-degree longitude by 0.5-degree latitude and at 72 levels, extending to 0.01 hPa. All products are generated at the native resolution of the

  1. A demographic dividend of the FP2020 Initiative and the SDG reproductive health target: Case studies of India and Nigeria.

    Science.gov (United States)

    Li, Qingfeng; Rimon, Jose G

    2018-02-22

    Background: The demographic dividend, defined as the economic growth potential resulting from favorable shifts in population age structure following rapid fertility decline, has been widely employed to advocate improving access to family planning. The current framework focuses on the long-term potential, while the short-term benefits may also help persuade policy makers to invest in family planning. Methods: We estimate the short- and medium-term economic benefits from two major family planning goals: the Family Planning 2020 (FP2020)'s goal of adding 120 million modern contraceptive users by 2020; Sustainable Development Goals (SDG) 3.7 of ensuring universal access to family planning by 2030. We apply the cohort component method to World Population Prospects and National Transfer Accounts data. India and Nigeria, respectively the most populous Asian and African country under the FP2020 initiative, are used as case studies. Results: Meeting the FP2020 target implies that on average, the number of children that need to be supported by every 100 working-age people would decrease by 8 persons in India and 11 persons in Nigeria in 2020; the associated reduction remains at 8 persons in India, but increases to 14 persons in Nigeria by 2030 under the SDG 3.7. In India meeting the FP2020 target would yield a saving of US$18.2 billion (PPP) in consumption expenditures for children and youth in the year 2020 alone, and that increased to US$89.7 billion by 2030. In Nigeria the consumption saved would be US$2.5 billion in 2020 and $12.9 billion by 2030. Conclusions: The tremendous economic benefits from meeting the FP2020 and SDG family planning targets demonstrate the cost-effectiveness of investment in promoting access to contraceptive methods. The gap already apparent between the observed and targeted trajectories indicates tremendous missing opportunities. Accelerated progress is needed to achieve the FP2020 and SDG goals and so reap the demographic dividend.

  2. Combined visual and semi-quantitative assessment of 123I-FP-CIT SPECT for the diagnosis of dopaminergic neurodegenerative diseases.

    Science.gov (United States)

    Ueda, Jun; Yoshimura, Hajime; Shimizu, Keiji; Hino, Megumu; Kohara, Nobuo

    2017-07-01

    Visual and semi-quantitative assessments of 123 I-FP-CIT single-photon emission computed tomography (SPECT) are useful for the diagnosis of dopaminergic neurodegenerative diseases (dNDD), including Parkinson's disease, dementia with Lewy bodies, progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration. However, the diagnostic value of combined visual and semi-quantitative assessment in dNDD remains unclear. Among 239 consecutive patients with a newly diagnosed possible parkinsonian syndrome who underwent 123 I-FP-CIT SPECT in our medical center, 114 patients with a disease duration less than 7 years were diagnosed as dNDD with the established criteria or as non-dNDD according to clinical judgment. We retrospectively examined their clinical characteristics and visual and semi-quantitative assessments of 123 I-FP-CIT SPECT. The striatal binding ratio (SBR) was used as a semi-quantitative measure of 123 I-FP-CIT SPECT. We calculated the sensitivity and specificity of visual assessment alone, semi-quantitative assessment alone, and combined visual and semi-quantitative assessment for the diagnosis of dNDD. SBR was correlated with visual assessment. Some dNDD patients with a normal visual assessment had an abnormal SBR, and vice versa. There was no statistically significant difference between sensitivity of the diagnosis with visual assessment alone and semi-quantitative assessment alone (91.2 vs. 86.8%, respectively, p = 0.29). Combined visual and semi-quantitative assessment demonstrated superior sensitivity (96.7%) to visual assessment (p = 0.03) or semi-quantitative assessment (p = 0.003) alone with equal specificity. Visual and semi-quantitative assessments of 123 I-FP-CIT SPECT are helpful for the diagnosis of dNDD, and combined visual and semi-quantitative assessment shows superior sensitivity with equal specificity.

  3. Regulation of protein kinase C-related kinase (PRK) signalling by the TPα and TPβ isoforms of the human thromboxane A2 receptor: Implications for thromboxane- and androgen- dependent neoplastic and epigenetic responses in prostate cancer.

    Science.gov (United States)

    O'Sullivan, Aine G; Mulvaney, Eamon P; Kinsella, B Therese

    2017-04-01

    The prostanoid thromboxane (TX) A 2 and its T Prostanoid receptor (the TP) are increasingly implicated in prostate cancer (PCa). Mechanistically, we recently discovered that both TPα and TPβ form functional signalling complexes with members of the protein kinase C-related kinase (PRK) family, AGC- kinases essential for the epigenetic regulation of androgen receptor (AR)-dependent transcription and promising therapeutic targets for treatment of castrate-resistant prostate cancer (CRPC). Critically, similar to androgens, activation of the PRKs through the TXA 2 /TP signalling axis induces phosphorylation of histone H3 at Thr11 (H3Thr11), a marker of androgen-induced chromatin remodelling and transcriptional activation, raising the possibility that TXA 2 -TP signalling can mimic and/or enhance AR-induced cellular changes even in the absence of circulating androgens such as in CRPC. Hence the aim of the current study was to investigate whether TXA 2 /TP-induced PRK activation can mimic and/or enhance AR-mediated cellular responses in the model androgen-responsive prostate adenocarcinoma LNCaP cell line. We reveal that TXA 2 /TP signalling can act as a neoplastic- and epigenetic-regulator, promoting and enhancing both AR-associated chromatin remodelling (H3Thr11 phosphorylation, WDR5 recruitment and acetylation of histone H4 at lysine 16) and AR-mediated transcriptional activation (e.g of the KLK3/prostate-specific antigen and TMPRSS2 genes) through mechanisms involving TPα/TPβ mediated-PRK1 and PRK2, but not PRK3, signalling complexes. Overall, these data demonstrate that TPα/TPβ can act as neoplastic and epigenetic regulators by mimicking and/or enhancing the actions of androgens within the prostate and provides further mechanistic insights into the role of the TXA 2 /TP signalling axis in PCa, including potentially in CRPC. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Metabolism and autoradiographic evaluation of [{sup 18}F]FE-CIT: a Comparison with [{sup 123}I]{beta}-CIT and [{sup 123}I]FP-CIT

    Energy Technology Data Exchange (ETDEWEB)

    Ettlinger, Dagmar E. [Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Haeusler, Daniela; Wadsak, Wolfgang [Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Girschele, Friedrich; Sindelar, Karoline M. [Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Mien, Leonhard-Key [Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Ungersboeck, Johanna [Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Viernstein, Helmut; Kletter, Kurt; Dudczak, Robert [Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Mitterhauser, Markus [Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria)], E-mail: markus.mitterhauser@meduniwien.ac.at

    2008-05-15

    Purpose: Since the late 1980s, cocaine analogues based on the phenyltropane structure, such as [{sup 11}C]CFT and [{sup 123}I]{beta}-CIT have been used for the imaging of the dopamine transporter. FE-CIT (fluoropropyl ester) and FP-CIT (N-fluoropropyl derivative) are further analogues. The aim of this study was to (1) evaluate and compare the metabolic stability of {beta}-CIT, FP-CIT and FE-CIT against carboxyl esterases and (2) evaluate selectivity of [{sup 18}F]FE-CIT compared to [{sup 123}I]{beta}-CIT and [{sup 123}I]FP-CIT using autoradiography. Methods: In vitro enzymatic hydrolysis assays were performed using different concentrations of {beta}-CIT, FE-CIT and FP-CIT with constant concentrations of carboxyl esterase. Autoradiography was performed on coronal 20-{mu}m rat brain sections incubated with different radioactivity concentrations of [{sup 123}I]{beta}-CIT, [{sup 123}I]FP-CIT or [{sup 18}F]FE-CIT and, additionally, with 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile [serotonin transporter (SERT)] and nisoxetine [norepinephrine transporter (NET)] for blocking experiments. Results: In vitro assays showed Michaelis-Menten constants of 175 {mu}mol ({beta}-CIT), 183 {mu}mol (FE-CIT) and 521 {mu}mol (FP-CIT). Limiting velocities were 0.1005 {mu}mol/min ({beta}-CIT), 0.1418 {mu}mol/min (FE-CIT) and 0.1308 {mu}mol/min (FP-CIT). This indicates a significantly increased stability of FP-CIT, whereas carboxyl esterase stability of {beta}-CIT and FE-CIT showed no significant difference. Autoradiographic analyses revealed a good correlation between dopamine transporter (DAT)-rich regions and the uptake pattern of FE-CIT. Blocking experiments showed a higher DAT selectivity for [{sup 18}F]FE-CIT than for the other two tracers. Conclusion: We found that (1) the metabolic stability of FE-CIT was comparable to that of {beta}-CIT, whereas FP-CIT showed higher resistance to enzymatic hydrolysis; and (2) the overall uptake pattern of [{sup 18}F]FE-CIT on

  5. One particle-hole excitations in p- and fp-shell nuclei

    International Nuclear Information System (INIS)

    Hees, A.G.M. van.

    1982-01-01

    Results are presented of shell model calculations of medium and light atomic nuclei. The influence of the allowance of one particle-hole excitations is investigated. This enables improved descriptions of intermediate mass nuclei in the fp-shell. For light p-shell nuclei one particle-hole excitations create exclusively situations with abnormal parity. The description of situations with normal parity is not changed by enlarging the model space. In the first chapter shell-model calculations are performed on the light Ni-isotopes (A = 57-59). One nucleon is allowed to be excited from the fsub(7/2) orbit to one of the other fp-shell orbits. The general observation in the enlarged model space is that one can use operators that require a much weaker 'renormalization' and the calculation requires only a selected set of matrix elements of the Hamiltonian. An additional advantage of the inclusion of one particle-hole excitations is that it allows a description of several intruder states, i.e. states that cannot be produced with the assumption of a closed 56 Ni core. In the second chapter the nuclei with mass number A = 52-55, i.e. a small number of holes in the 56 Ni core, are investigated similarly. In the third chapter much lighter nuclei (A = 4-16) are discussed. For a theoretical description of nonnormal-parity states one has to admit the excitation of at least one nucleon to a higher harmonic-oscillator major-shell. (Auth.)

  6. [{sup 123}]FP-CIT SPECT scans initially rated as normal became abnormal over time in patients with probable dementia with Lewy bodies

    Energy Technology Data Exchange (ETDEWEB)

    Zande, J.J. van der; Scheltens, P.; Lemstra, A.W. [VU Medical Center Alzheimer Center, Amsterdam (Netherlands); Booij, J. [Academic Medical Center, Department of Nuclear Medicine, Amsterdam (Netherlands); Raijmakers, P.G.H.M. [VU Medical Center, Department of Nuclear Medicine, Amsterdam (Netherlands)

    2016-06-15

    Decreased striatal dopamine transporter (DAT) binding on SPECT imaging is a strong biomarker for the diagnosis of dementia with Lewy bodies (DLB). There is still a lot of uncertainty about patients meeting the clinical criteria for probable DLB who have a normal DAT SPECT scan (DLB/S-). The aim of this study was to describe the clinical and imaging follow-up in these patients, and compare them to DLB patients with abnormal baseline scans (DLB/S+). DLB patients who underwent DAT imaging ([{sup 123}I]FP-CIT SPECT) were selected from the Amsterdam Dementia Cohort. All [{sup 123}I]FP-CIT SPECT scans were evaluated independently by two nuclear medicine physicians and in patients with normal scans follow-up imaging was obtained. We matched DLB/S- patients for age and disease duration to DLB/S+ patients and compared their clinical characteristics. Of 67 [{sup 123}I]FP-CIT SPECT scans, 7 (10.4 %) were rated as normal. In five DLB/S- patients, a second [{sup 123}I]FP-CIT SPECT was performed (after on average 1.5 years) and these scans were all abnormal. No significant differences in clinical characteristics were found at baseline. DLB/S- patients could be expected to have a better MMSE score after 1 year. This study was the first to investigate DLB patients with the initial [{sup 123}I]FP-CIT SPECT scan rated as normal and subsequent scans during disease progression rated as abnormal. We hypothesize that DLB/S- scans could represent a relatively rare DLB subtype with possibly a different severity or spread of alpha-synuclein pathology (''neocortical predominant subtype''). In clinical practice, if an alternative diagnosis is not imminent in a DLB/S- patient, repeating [{sup 123}I]FP-CIT SPECT should be considered. (orig.)

  7. Assessment of affinities of beta-CIT, beta-CIT-FE, and beta-CIT-FP for monoamine transporters permanently expressed in cell lines

    International Nuclear Information System (INIS)

    Okada, Tomoya; Fujita, Masahiro; Shimada, Shoichi; Sato, Kohji; Schloss, Patrick; Watanabe, Yoshiyuki; Itoh, Yasushi; Tohyama, Masaya; Nishimura, Tsunehiko

    1998-01-01

    We investigated the effects of three cocaine analogs, beta-CIT (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane), beta-CIT-FE (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-N-(2-fluoroethyl)-nortropane), and beta-CIT-FP (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane), on the uptake of [ 3 H]dopamine(DA), serotonin(5-HT), and 1-norepinephrine (NE) using cell lines permanently expressing DA, 5-HT, and NE transporters, respectively, to determine their affinities for these three transporters. We generated cell lines stably expressing DA, 5-HT, and NE transporters, respectively, by the Chen-Okayama method, and then tested the abilities of (-)cocaine, beta-CIT, beta-CIT-FE, beta-CIT-FP, and clomipramine to inhibit the uptake of [ 3 H]DA, 5-HT, and 1-NE. Ki values of beta-CIT, beta-CIT-FE, and beta-CIT-FP for [ 3 H]DA, 5-HT, 1-NE uptake were 6, 29, and 33 nM, 91, 133, and 130 nM, and 28, 113 and 70 nM, respectively, whereas those of cocaine and clomipramine were 316, 581, and 176 nM and > 10,000, 437, and 851 nM, respectively. Beta-CIT, beta-CIT-FE, and beta-CIT-FP were shown to be potent DA, 5-HT, and NE uptake inhibitors. Beta-CIT and beta-CIT-FP were highly potent and selective dopamine uptake inhibitors, and therefore might be useful for imaging of DA transporter with single photon emission computed tomography (SPECT) or positron emission tomography (PET)

  8. Instrument development in support of Falcon and Phebus-FP

    International Nuclear Information System (INIS)

    Bowsher, B.R.; Brunning, J.

    1992-12-01

    This review has been undertaken to identify various on-line instruments and post-test analytical techniques that may improve the quality of data from both the Falcon Integral Test Programme and Phebus-FP. Particular emphasis is placed on the use of in-situ techniques to provide mass-based data on the aerodynamic properties of the aerosol and fission product-surface interactions. The principles of the following techniques are reviewed: cascade impactors, tapered element oscillating microbalance, condensation nucleus counter, Knudsen cell mass spectrometry, diffuse reflectance infrared Fourier transform spectrometry and secondary-ion mass spectrometry. These methods are currently being used in the Falcon experimental programme. (author)

  9. Long-term orbital period behaviour of low mass ratio contact binaries GR Vir and FP Boo

    Science.gov (United States)

    Ćetinkaya, Halil; Soydugan, Faruk

    2017-02-01

    In this study, we investigated orbital period variations of two low mass ratio contact binaries GR Vir and FP Boo based on published minima times. From the O-C analysis, it was found that FP Boo indicates orbital period decrease while the period of GR Vir is increasing. Mass transfer process was used to explain increase and decrease in the orbital periods. In the O-C diagrams of both systems periodic variations also exist. Cyclic changes can be explained as being the result of a light-travel time effect via a third component around the eclipsing binaries. In order to interpret of cyclic orbital period changes for GR Vir, which has late-type components, possible magnetic activity cycles of the components have been also considered.

  10. European multicentre database of healthy controls for [(123)I]FP-CIT SPECT (ENC-DAT)

    DEFF Research Database (Denmark)

    Varrone, Andrea; Dickson, John C; Tossici-Bolt, Livia

    2013-01-01

    of quantification is the availability of normative data, considering possible age and gender effects on DAT availability. The aim of the European Normal Control Database of DaTSCAN (ENC-DAT) study was to generate a large database of [(123)I]FP-CIT SPECT scans in healthy controls....

  11. Stress Alone or associated with Ethanol Induces Prostanoid Release in Rat Aorta via α2-Adrenoceptor

    Energy Technology Data Exchange (ETDEWEB)

    Baptista, Rafaela de Fátima Ferreira [Departamento de Farmacologia - Instituto de Biociências - Universidade Estadual Paulista - UNESP - São Paulo, SP (Brazil); Laboratório de Farmacologia - Faculdade de Medicina de Marília - FAMEMA, SP (Brazil); Taipeiro, Elane de Fátima [Laboratório de Farmacologia - Faculdade de Medicina de Marília - FAMEMA, SP (Brazil); Queiroz, Regina Helena Costa [Departamento de Análise Clínica - Toxicológica e Ciência de Alimentos - Faculdade de Ciências Farmacêuticas - USP, São Paulo, SP (Brazil); Chies, Agnaldo Bruno [Departamento de Farmacologia - Instituto de Biociências - Universidade Estadual Paulista - UNESP - São Paulo, SP (Brazil); Laboratório de Farmacologia - Faculdade de Medicina de Marília - FAMEMA, SP (Brazil); Cordellini, Sandra, E-mail: cordelli@ibb.unesp.br [Departamento de Farmacologia - Instituto de Biociências - Universidade Estadual Paulista - UNESP - São Paulo, SP (Brazil)

    2014-03-15

    Stress and ethanol are both, independently, important cardiovascular risk factors. To evaluate the cardiovascular risk of ethanol consumption and stress exposure, isolated and in association, in male adult rats. Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and stress/ethanol. Concentration-responses curves to noradrenaline - in the absence and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were determined in thoracic aortas with and without endothelium. EC50 and maximum response (n=8-12) were compared using two-way ANOVA/Bonferroni method. Either stress or stress in association with ethanol consumption increased the noradrenaline maximum responses in intact aortas. This hyper-reactivity was eliminated by endothelium removal or by the presence of either indomethacin or yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol consumption did not alter the reactivity to noradrenaline. The phenylephrine responses in aortas both with and without endothelium also remained unaffected regardless of protocol. Chronic stress increased rat aortic responses to noradrenaline. This effect is dependent upon the vascular endothelium and involves the release of vasoconstrictor prostanoids via stimulation of endothelial alpha-2 adrenoceptors. Moreover, chronic ethanol consumption appeared to neither influence noradrenaline responses in rat thoracic aorta, nor did it modify the increase of such responses observed as a consequence of stress exposure.

  12. Stress Alone or associated with Ethanol Induces Prostanoid Release in Rat Aorta via α2-Adrenoceptor

    International Nuclear Information System (INIS)

    Baptista, Rafaela de Fátima Ferreira; Taipeiro, Elane de Fátima; Queiroz, Regina Helena Costa; Chies, Agnaldo Bruno; Cordellini, Sandra

    2014-01-01

    Stress and ethanol are both, independently, important cardiovascular risk factors. To evaluate the cardiovascular risk of ethanol consumption and stress exposure, isolated and in association, in male adult rats. Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and stress/ethanol. Concentration-responses curves to noradrenaline - in the absence and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were determined in thoracic aortas with and without endothelium. EC50 and maximum response (n=8-12) were compared using two-way ANOVA/Bonferroni method. Either stress or stress in association with ethanol consumption increased the noradrenaline maximum responses in intact aortas. This hyper-reactivity was eliminated by endothelium removal or by the presence of either indomethacin or yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol consumption did not alter the reactivity to noradrenaline. The phenylephrine responses in aortas both with and without endothelium also remained unaffected regardless of protocol. Chronic stress increased rat aortic responses to noradrenaline. This effect is dependent upon the vascular endothelium and involves the release of vasoconstrictor prostanoids via stimulation of endothelial alpha-2 adrenoceptors. Moreover, chronic ethanol consumption appeared to neither influence noradrenaline responses in rat thoracic aorta, nor did it modify the increase of such responses observed as a consequence of stress exposure

  13. Measurements at FP3 in support of pecan scientific objectives using MPL-111 lidar

    Science.gov (United States)

    Pozsonyi, Kristen; Midzak, Natalie; Prestine, Christina; Clark, Richard

    2018-04-01

    This paper will report on the data collected by a Sigma Space Micropulse Lidar (MPL-111), and how these measurements, when integrated with other data, helps to inform our analysis of two cases of the Great Plains nocturnal Low-Level Jet (LLJ) in the vicinity of FP3.

  14. Challenges in Implementing FP7 Projects in the Public Institutions

    Directory of Open Access Journals (Sweden)

    Viorel VULTURESCU

    2012-06-01

    Full Text Available National Authority for Scientific Research (ANCS and Executive Unit for Higher Education, Research and Development and Innovation Funding (UEFISCDI participate to several projects funded under the Framework Programmes, since 1998. The staff from each the two organisations participating in projects are merely the same, typically from “international cooperation” departments. In each of the two organisations, dedicated teams were set and a distinct specialization emerged. In this respect, dedicated procedures and good practices in project management were developed. Even the Framework Programs had different structures and the focused was different (e.g. knowledge creation, EU problem solving, scientific support for policies and programs, etc., the funding instruments (projects were not radically different from a Framework Program to another, so the staff could gain experience in managing this type of projects. Experience and expertise gained during this long period of time led to definition of a general framework within the two institutions and setting up of a general guideline for participation to this type of projects. The main dimensions of this framework are: project team organization, project management process, managing results and risk, organisational framework, good practices, factors which ensure success in project implementation.The paper presents a specific framework for FP 7 project implementation and how this framework is applied by both organisations, a set of rules and procedures that should be followed by any organisation, in particular governmental ones, participating in FP 7 projects and a set of good practices developed by ANCS and UEFISCDI.

  15. Measurements at FP3 in support of pecan scientific objectives using MPL-111 lidar

    Directory of Open Access Journals (Sweden)

    Pozsonyi Kristen

    2018-01-01

    Full Text Available This paper will report on the data collected by a Sigma Space Micropulse Lidar (MPL-111, and how these measurements, when integrated with other data, helps to inform our analysis of two cases of the Great Plains nocturnal Low-Level Jet (LLJ in the vicinity of FP3.

  16. Protease-activated receptor-2 activation exaggerates TRPV1-mediated cough in guinea pigs.

    Science.gov (United States)

    Gatti, Raffaele; Andre, Eunice; Amadesi, Silvia; Dinh, Thai Q; Fischer, Axel; Bunnett, Nigel W; Harrison, Selena; Geppetti, Pierangelo; Trevisani, Marcello

    2006-08-01

    A lowered threshold to the cough response frequently accompanies chronic airway inflammatory conditions. However, the mechanism(s) that from chronic inflammation results in a lowered cough threshold is poorly understood. Irritant agents, including capsaicin, resiniferatoxin, and citric acid, elicit cough in humans and in experimental animals through the activation of the transient receptor potential vanilloid 1 (TRPV1). Protease-activated receptor-2 (PAR2) activation plays a role in inflammation and sensitizes TRPV1 in cultured sensory neurons by a PKC-dependent pathway. Here, we have investigated whether PAR2 activation exaggerates TRPV1-dependent cough in guinea pigs and whether protein kinases are involved in the PAR2-induced cough modulation. Aerosolized PAR2 agonists (PAR2-activating peptide and trypsin) did not produce any cough per se. However, they potentiated citric acid- and resiniferatoxin-induced cough, an effect that was completely prevented by the TRPV1 receptor antagonist capsazepine. In contrast, cough induced by hypertonic saline, a stimulus that provokes cough in a TRPV1-independent manner, was not modified by aerosolized PAR2 agonists. The PKC inhibitor GF-109203X, the PKA inhibitor H-89, and the cyclooxygenase inhibitor indomethacin did not affect cough induced by TRPV1 agonists, but abated the exaggeration of this response produced by PAR2 agonists. In conclusion, PAR2 stimulation exaggerates TRPV1-dependent cough by activation of diverse mechanism(s), including PKC, PKA, and prostanoid release. PAR2 activation, by sensitizing TRPV1 in primary sensory neurons, may play a role in the exaggerated cough observed in certain airways inflammatory diseases such as asthma and chronic obstructive pulmonary disease.

  17. Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [123I]FP-CIT and a dedicated small animal SPECT

    International Nuclear Information System (INIS)

    Nikolaus, Susanne; Wirrwar, Andreas; Antke, Christina; Arkian, Shahram; Mueller, Hans-Wilhelm; Larisch, Rolf; Schramm, Nils

    2005-01-01

    The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [ 123 I]FP-CIT. [ 123 I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [ 123 I]FP-CIT scans with bone metabolism and perfusion scans obtained with 99m Tc-DPD and 99m Tc-tetrofosmin, respectively. As these tracers do not pass the blood-brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [ 123 I]FP-CIT scans with images of brain perfusion obtained with 99m Tc-HMPAO. Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V '' 3 ) of 0.24±0.26 (mean ± SD) and 1.09±0.42, respectively (ttest, two-tailed, p '' 3 values amounted to 0.05±0.28 (methylphenidate) and 0.3±0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [ 123 I]FP-CIT accumulation. The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [ 123 I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinson's and Huntington's disease, may be feasible using SPECT radioligands and small animal imaging systems. (orig.)

  18. Machine learning models for the differential diagnosis of vascular parkinsonism and Parkinson's disease using [{sup 123}I]FP-CIT SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Huertas-Fernandez, I.; Benitez-Rivero, S.; Jesus, S.; Caceres-Redondo, M.T.; Martin-Rodriguez, J.F.; Carrillo, F. [Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia y Neurofisiologia Clinica, Seville (Spain); Garcia-Gomez, F.J.; Marin-Oyaga, V.A.; Lojo, J.A. [Hospital Universitario Virgen del Rocio, Servicio de Medicina Nuclear, UDIM, Seville (Spain); Garcia-Solis, D. [Hospital Universitario Virgen del Rocio, Servicio de Medicina Nuclear, UDIM, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain); Mir, P. [Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia y Neurofisiologia Clinica, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain)

    2015-01-15

    The study's objective was to develop diagnostic predictive models using data from two commonly used [{sup 123}I]FP-CIT SPECT assessment methods: region-of-interest (ROI) analysis and whole-brain voxel-based analysis. We included retrospectively 80 patients with vascular parkinsonism (VP) and 164 patients with Parkinson's disease (PD) who underwent [{sup 123}I]FP-CIT SPECT. Nuclear-medicine specialists evaluated the scans and calculated bilateral caudate and putamen [{sup 123}I]FP-CIT uptake and asymmetry indices using BRASS software. Statistical parametric mapping (SPM) was used to compare the radioligand uptake between the two diseases at the voxel level. Quantitative data from these two methods, together with potential confounding factors for dopamine transporter availability (sex, age, disease duration and severity), were used to build predictive models following a tenfold cross-validation scheme. The performance of logistic regression (LR), linear discriminant analysis and support vector machine (SVM) algorithms for ROI data, and their penalized versions for SPM data (penalized LR, penalized discriminant analysis and SVM), were assessed. Significant differences were found in the ROI analysis after covariate correction between VP and PD patients in [{sup 123}I]FP-CIT uptake in the more affected side of the putamen and the ipsilateral caudate. Age, disease duration and severity were also found to be informative in feeding the statistical model. SPM localized significant reductions in [{sup 123}I]FP-CIT uptake in PD with respect to VP in two specular clusters comprising areas corresponding to the left and right striatum. The diagnostic predictive accuracy of the LR model using ROI data was 90.3 % and of the SVM model using SPM data was 90.4 %. The predictive models built with ROI data and SPM data from [{sup 123}I]FP-CIT SPECT provide great discrimination accuracy between VP and PD. External validation of these methods is necessary to confirm their

  19. Nissei incas system (FP-Plan) which databased the skilled sense and experiences in molding metal design. Kanagata sekkei ni okeru kan ya keiken wo data base kashita Nissei incas system (FP-plan)

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, K. (Nissei Plastic Industrial Co. Ltd., Nagano (Japan))

    1992-01-01

    Mold System Department of Nissei Resin Industies Co. has developed NISSEI INCAS SYSTEM, which is a CAD/CAM/CAE system specially for injection metal molding. Generally, high analysis methods such as flow analysis method have been considered for CAE, though, when making it to be linked with designing works for injection molding metals, economic conditions will not make a balance. Since authors have judged that to make an accurate mold metal drawing more quickly, before adopting such kind of flow analysis, more inportant and fundamental problems might be remained, they have started to develope their own system called FP-PLAN. This system, for example, is a software, which paying mainly attention to the most important and common problems for molding metal design to be solved, such as setting of shrinking factor, gate and runner design, estimation of cavity inside pressure, etc. Specially, they have developed only small molding products (product volume shall be under 200 cm {sup 3}). In this report, outlines of FP-PLAN such as the characteristics and programs have been intrduced. 4 figs., 2 tabs.

  20. Prepulse inhibition is associated with attention, processing speed, and 123I-FP-CIT SPECT in Parkinson's disease

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Biernat, Heidi B; Nikolic, Miki

    2014-01-01

    BACKGROUND: Prepulse inhibition is a measure of sensorimotor gating, which reflects the ability to filter or 'gate' irrelevant information. Prepulse inhibition is dramatically altered in basal ganglia disorders associated with dysfunction in the midbrain dopaminergic system, and corresponding......'s disease have been extensively studied in relation to motor function, less is known about the potential role of sensorimotor processes in cognitive function. OBJECTIVE: We investigated the relationship between prepulse inhibition, cognition and nigrostriatal dysfunction, as measured with 123I......-FP-CIT-SPECT scanning, in patients with Parkinson's disease. METHODS: 38 Parkinson patients were assessed with prepulse inhibition, neuropsychological tests, and neurological investigation. A subset of these patients underwent 123I-FP-CIT-SPECT scanning. RESULTS: Patients with a higher level of prepulse inhibition...

  1. Sensitivity analysis for CORSOR models simulating fission product release in LOFT-LP-FP-2 severe accident experiment

    Energy Technology Data Exchange (ETDEWEB)

    Hoseyni, Seyed Mohsen [Islamic Azad Univ., Tehran (Iran, Islamic Republic of). Dept. of Basic Sciences; Islamic Azad Univ., Tehran (Iran, Islamic Republic of). Young Researchers and Elite Club; Pourgol-Mohammad, Mohammad [Sahand Univ. of Technology, Tabriz (Iran, Islamic Republic of). Dept. of Mechanical Engineering; Yousefpour, Faramarz [Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of)

    2017-03-15

    This paper deals with simulation, sensitivity and uncertainty analysis of LP-FP-2 experiment of LOFT test facility. The test facility simulates the major components and system response of a pressurized water reactor during a LOCA. MELCOR code is used for predicting the fission product release from the core fuel elements in LOFT LP-FP-2 experiment. Moreover, sensitivity and uncertainty analysis is performed for different CORSOR models simulating release of fission products in severe accident calculations for nuclear power plants. The calculated values for the fission product release are compared under different modeling options to the experimental data available from the experiment. In conclusion, the performance of 8 CORSOR modeling options is assessed for available modeling alternatives in the code structure.

  2. Postirradiation examination results from the LP-FP-2 center fuel module

    International Nuclear Information System (INIS)

    Jensen, S.M.; Akers, D.W.

    1990-01-01

    The LP-FP-2 experiment was conducted on July 9, 1985 in the Loss of Fluid Test (LOFT) facility located at the Idaho National Engineering Laboratory (INEL). The primary purpose of this experiment was to provide information of the release, transport, and deposition of fission products and aerosols during a sever core damage event performed in a large scale nuclear reactor facility. Postirradiation nondestructive and destructive examinations of the fuel bundle provided information to assist in achieving this objective, as well as providing information on the material behavior and interactions that occurred within the fuel bundle during this sever core damage experiment. This was a large-scale integral test, incorporating an 11 x 11 array of fuel rods, control rods, and instrumentation tubes, with an active core length of 1.68 m. Peak temperatures in the fuel bundle exceeded 2100 K or approximately 4.5 min, with localized peak temperatures exceeding the melting point of the UO 2 fuel (3120 K). Large amounts of zircaloy oxidation and material relocation occurred during the experiment. The transient phase was terminated by a rapid reflood of cooling water, which resulted in significant oxidation and hydrogen generation. Zircaloy oxidation during the reflood period caused a rapid temperature excursion to occur in the upper two-thirds of the fuel bundle. This article summarizes the data and analysis from the postirradiation examinations of the LP-FP-2 fuel bundle. 12 refs., 39 figs., 8 tabs

  3. Clinical Significance of F 18 FP CIT Dual Time Point PET Imaging in Idiopathic Parkinson's Disease

    International Nuclear Information System (INIS)

    Oh, Jin Kyoung; Yoo, Ik Dong; Seo, Ye Young; Chung, Youg An; Yoo, Ie Ryung; Kim, Sung Hoon; Song, In Uk

    2011-01-01

    The purpose of this study was to investigate the diagnostic value of dual time point F 18 FP CIT PET imaging in idiopathic Parkinson's disease (PD). Twenty four patients with PD (mean age 69.6) and 18 healthy people (mean age 70.26) underwent two sequential PET/CT scans (dual time point imaging) at 90 and 210 min after F 18 FP CIT injection. Tracer activity of region of interest was measured in the caudate, putamen and a reference region in the brain from both time points. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were obtained in the control group. The percent change in tracer activity between 90 and 210 min images was calculated. The SOR values and the percent change in tracer activity were compared between the patients and healthy control group. The SOR values for the caudate, anterior and posterior putamen at both 90 and 210 min images were significantly reduced in the patients with PD. The lowest P value was obtained for the anterior and posterior putamen (p<0.001) at both time points. There were significant differences of the percent change in tracer activity for the anterior and posterior putamen in the two groups (p=0.01) F 18 FP CIT PET scans at 90 and 210 min after injection are both able to diagnose PD. Therefore, the 90 min image by itself in sufficient for diagnosing PD.

  4. Applicability of Phebus FP results to severe accident safety evaluations and management measures

    International Nuclear Information System (INIS)

    Schwarz, M.; Clement, B.; Jones, A.V.

    2001-01-01

    The international Phebus FP (Fission Product) programme is the largest research programme in the world investigating core degradation and radioactive product release should a core meltdown accident occur in a light water reactor plant. Three integral experiments have already been performed. The experimental database obtained so far contains a wealth of information to validate the computer codes used for safety and accident management assessment

  5. Inventory of the patents and publications of FP7 projects in the field of ICT

    NARCIS (Netherlands)

    Jacob, J.; Sanditov, Bulat; Smirnov, Evgueni; Wintjes, Rene; Surpatean, A.; Notten, Ad; Sasso, Simone

    2015-01-01

    The inventory includes data on 295 patents and 18,158 publications resulting from FP7 funded projects in the field of ICT (ICT theme within Cooperation Programme and eInfrastructures within Capacities Programme). The period covered is 2007 - 2013. Patents and publications have been reported by

  6. Applications research in ultrasonic testing of carbon fiber composite based on an optical fiber F-p sensor

    Science.gov (United States)

    Shan, Ning

    2016-10-01

    Carbon fiber composite is widely applied to the field of aerospace engineering because of its excellent performance. But it will be able to form more defects in the process of manufacturing inevitably on account of unique manufacturing process. Meanwhile it has sophisticated structure and services in the bad environment long time. The existence of defects will be able to cause the sharp decline in component's performance when the defect accumulates to a certain degree. So the reliability and safety test demand of carbon fiber composite is higher and higher. Ultrasonic testing technology is the important means used for characteristics of component inspection of composite materials. Ultrasonic information detection uses acoustic transducer generally. It need coupling agent and is higher demand for the surface of sample. It has narrow frequency band and low test precision. The extrinsic type optical fiber F-P interference cavity structure is designed to this problem. Its optical interference model is studied. The initial length of F-P cavity is designed. The realtime online detection system of carbon fiber composite is established based on optical fiber F-P Ultrasound sensing technology. Finally, the testing experiment study is conducted. The results show that the system can realize real-time online detection of carbon fiber composite's defect effectively. It operates simply and realizes easily. It has low cost and is easy to practical engineering.

  7. Euratom framework programme research in reactor safety main achievements of FP-4 ('94-'98), some preliminary results of FP-5 ('98-'02) and prospects for beyond 2002

    Energy Technology Data Exchange (ETDEWEB)

    Goethem, G. van; Martin Bermejo, J.; Zurita, A.; Lemaitre, P. [Commission of the European Communities, Brussels (BE). Directorate General for Science, Research and Development (DG 12)

    2001-07-01

    In this paper an overview is given of the most important aspects of the research activities organised by the European union (EU) in reactor safety, more specifically in the area ''Operational Safety of Existing Installations'', which is one of the 4 areas of the key action Nuclear Fission in the 5th Euratom framework programme (FP-5). In the introduction, a short description is given of the EU needs and the new boundary conditions for Euratom research. In the next 7 sections, the attention is drawn to a series of technical and socio-economical facts, which generate needs at the EU level and hence justify some actions - especially in terms of research - at the Commission level. The following needs have been identified and are proposed for discussion: to maintain the nuclear option open in order to ensure flexibility in energy supply; to maintain scientific and technical competence; to maintain industrial competitiveness and to prepare the next generation of reactors; to maintain a broad nuclear expertise covering both energetic and non-energetic applications; to develop environment-friendly sustainable solutions for the wastes; to share and improve the safety culture amongst the EU countries and the CEECs; and finally, to focus on public benefit and on added European value in Euratom research actions. A brief overview then is given of the European response - in terms of research - offered up to 2002 to contribute to meet some of the above needs, i.e. the Euratom research actions under FP-4 ('94-'98) and FP-5 ('98-'02). As far as the future beyond 2002 is concerned, the challenge to Euratom research is to identify networks of excellence and to reorganize itself in line with the new ERA concept (European research area). Finally conclusions are drawn on the perceived need to improve the fitness-for-purpose of Euratom research actions in the ''changing world'' and to rethink accordingly the organisation of

  8. An attempt for revision of JNDC FP decay data file

    International Nuclear Information System (INIS)

    Katakura, Jun-ichi; Matsumoto, Zyun-itiro; Akiyama, Masatsugu; Yoshida, Tadashi; Nakasima, Ryozo.

    1984-06-01

    Some improvement of JNDC FP Decay Data File is tried by reexamining the decay scheme for several nuclides, since slight discrepancies are seen in detailed comparison of decay powers. As a results, it is found that the average beta- and gamma-energies should be modified for 88 Rb and 143 La among the nuclides reexamined in the present study. The JNDC file modified in 88 Rb and 143 La gives better agreement in most cases with experiments than the original JNDC file for cooling times longer than a few thousands seconds. However, the discrepancy for cooling times from a few hundreds to about 1500 seconds still remains. (author)

  9. Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [{sup 123}I]FP-CIT and a dedicated small animal SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Nikolaus, Susanne; Wirrwar, Andreas; Antke, Christina; Arkian, Shahram; Mueller, Hans-Wilhelm; Larisch, Rolf [Heinrich-Heine University, Clinic of Nuclear Medicine, Duesseldorf (Germany); Schramm, Nils [Research Center Juelich, Central Laboratory for Electronics, Juelich (Germany)

    2005-03-01

    The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [{sup 123}I]FP-CIT. [{sup 123}I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [{sup 123}I]FP-CIT scans with bone metabolism and perfusion scans obtained with {sup 99m}Tc-DPD and {sup 99m}Tc-tetrofosmin, respectively. As these tracers do not pass the blood-brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [{sup 123}I]FP-CIT scans with images of brain perfusion obtained with {sup 99m}Tc-HMPAO. Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V''{sub 3}) of 0.24{+-}0.26 (mean {+-} SD) and 1.09{+-}0.42, respectively (ttest, two-tailed, p<0.0001). Cortical V''{sub 3} values amounted to 0.05{+-}0.28 (methylphenidate) and 0.3{+-}0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [{sup 123}I]FP-CIT accumulation. The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [{sup 123}I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinson's and Huntington's disease, may be feasible using SPECT radioligands and

  10. Chronic motor cortex stimulation in patients with advanced Parkinson's disease and effects on striatal dopaminergic transmission as assessed by 123I-FP-CIT SPECT: a preliminary report.

    Science.gov (United States)

    Di Giuda, Daniela; Calcagni, Maria L; Totaro, Manuela; Cocciolillo, Fabrizio; Piano, Carla; Soleti, Francesco; Fasano, Alfonso; Cioni, Beatrice; Bentivoglio, Anna R; Giordano, Alessandro

    2012-09-01

    The objective of this study was to assess striatal dopamine transporter availability in patients with advanced Parkinson's disease (PD) before and after 13 months of unilateral extradural motor cortex stimulation (EMCS) with [123I]N-ω-fluoropropyl-2-β-carbo-methoxy-3-β-(4-iodophenyl)nortropane single photon emission computed tomography (123I-FP-CIT SPECT). Six PD patients (five women and one man, aged 63.2 ± 5.6 years) underwent 123I-FP-CIT SPECT and clinical evaluation [Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Quality of Life Scale (PDQL)] preoperatively, 8 and 13 months after EMCS. Striatum-to-occipital cortex, caudate-to-occipital cortex and putamen-to-occipital cortex 123I-FP-CIT uptake ratios were calculated using the region of interest method. Total and part III UPDRS scores significantly decreased at 8 and 13 months after stimulation (P=0.02 and 0.04, respectively); UPDRS part II and PDQL scores improved after 13 months (P=0.02 and 0.04, respectively). No significant differences in 123I-FP-CIT uptake ratios between baseline and follow-up were found in the examined regions. However, a progressive reduction in 123I-FP-CIT uptake ratios in the striatum contralateral to the implant was found. In contrast, no further decrease in 123I-FP-CIT uptake ratios was detected in the striatum ipsilateral to the implant. There were no correlations between changes in 123I-FP-CIT uptake ratios with disease duration, changes in medication dosage and motor UPDRS scores. Despite a small but highly selected sample of advanced PD patients, our results showed that no further dopamine transporter reduction occurred in the striatum ipsilateral to the implant side. This finding could lead to the hypothesis that EMCS might elicit a 'neuroprotective' effect, as suggested by significant clinical benefits.

  11. Using novel computer-assisted linguistic analysis techniques to assess the timeliness and impact of FP7 Health’s research – a work in progress report

    Energy Technology Data Exchange (ETDEWEB)

    Stanciauskas, V.; Brozaitis, H.; Manola, N.; Metaxas, O.; Galsworthy, M.

    2016-07-01

    This paper presents the ongoing developments of the ex-post evaluation of the Health theme in FP7 which will be finalised in early 2017. the evaluation was launched by DG Research and Innovation, European Commission. Among other questions the evaluation asked to assess the structuring effect of FP7 Health on the European Research Area dnd the timeliness of the research performed. To this end the evalaution team has applied two innovative computerassisted linguistic analysis techniques to adderss these questions, including dynamic topic modelling and network analysis of co-publications. The topic model built for this evaluation contributed to comprehensive mapping of FP7 Health's research activities and building of a dynamic topic model that has not been attempted in previous evalautions of the Framework Programmes. Our applied network analysiswas of co-publications proved to be a powerful tool in determining the structuring effect of the FP7 Health to a level of detail which was again not implemented in previous evaluations of EU-funded research programmes. (Author)

  12. Repeated administration of D-amphetamine induces loss of [123I]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study

    International Nuclear Information System (INIS)

    Booij, Jan; Bruin, Kora de; Gunning, W. Boudewijn

    2006-01-01

    In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in amphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of D-AMPH or methamphetamine (METH) may induce loss of binding to striatal DATs in rats by using an experimental biodistribution study design and a SPECT tracer for the DAT ([ 123 I]FP-CIT). Methods: Groups of male rats (n=10 per group) were treated with D-AMPH (10 mg/kg body weight), METH (10 mg/kg body weight), or saline, twice a day for 5 consecutive days. Five days later, [ 123 I]FP-CIT was injected intravenously, and 2 h later, the rats were sacrificed and radioactivity was assayed. Results: In D-AMPH but not METH-treated rats, striatal [ 123 I]FP-CIT uptake was significantly lower (approximately 17%) than in the control group. Conclusion: These data show that [ 123 I]FP-CIT can be used to detect AMPH-induced changes in DAT binding and may validate the use of DAT radiotracers to study AMPH-induced changes in striatal DAT binding in vivo

  13. Clinical correlation of the binding potential with {sup 123}I-FP-CIT in de novo idiopathic Parkinson's disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Berti, Valentina; Pupi, Alberto; Vanzi, Eleonora; Cristofaro, Maria Teresa de; Pellicano, Giannantonio; Mungai, Francesco [University of Florence, Clinical Pathophysiology, Florence (Italy); Ramat, Silvia; Marini, Paolo; Sorbi, Sandro [University of Florence, Neurological and Psychiatric Sciences, Florence (Italy)

    2008-12-15

    The aim of this study was to evaluate the accuracy of different single-photon emission computed tomography (SPECT) reconstruction techniques in measuring striatal N-{omega}-fluoropropyl-2{beta}-carbomethoxy-3{beta}-4-[{sup 123}I]iodophenyl-nortropane ({sup 123}I-FP-CIT) binding in de novo Parkinson's disease (PD) patients, in order to find a correlation with clinical scales of disease severity in the initial phases of disease. Thirty-six de novo PD patients underwent {sup 123}I-FP-CIT SPECT and MRI scan. SPECT data were reconstructed with filtered back projection (FBP), with an iterative algorithm (ordered subset expected maximization, OSEM) and with a method previously developed in our institution, called least-squares (LS) method. The ratio of specific to non-specific striatal {sup 123}I-FP-CIT binding (binding potential, BP) was used as the outcome measure with all the reconstruction methods (BP{sub FBP}, BP{sub OSEM}, BP{sub LS}). The range of values of striatal BP{sub LS} was significantly greater than BP{sub FBP} and BP{sub OSEM}. For all striatal regions, estimates of BP{sub FBP} correlated well with BP{sub OSEM} (r=0.84) and with BP{sub LS} (r=0.64); BP{sub OSEM} correlated significantly with BP{sub LS} (r=0.76). A good correlation was found between putaminal BP{sub LS} and Hoen and Yahr, Unified PD Rating Scale (UPDRS) and lateralized UPDRS motor scores (r=-0.46, r=-0.42, r=-0.39, respectively). Neither putaminal BP{sub FBP} nor putaminal BP{sub OSEM} correlated with any of these motor scores. In de novo PD patients, {sup 123}I-FP-CIT BP values derived from FBP and OSEM reconstruction techniques do not permit to differentiate PD severity. The LS method instead finds a correlation between striatal BP and disease severity scores. The results of this study support the use of {sup 123}I-FP-CIT BP values estimated with the LS method as a biomarker of PD severity. (orig.)

  14. Prostaglandin E2 EP2 Receptor Deletion Attenuates Intracerebral Hemorrhage-Induced Brain Injury and Improves Functional Recovery

    Directory of Open Access Journals (Sweden)

    Jenna L. Leclerc

    2015-04-01

    Full Text Available Intracerebral hemorrhage (ICH is a devastating type of stroke characterized by bleeding into the brain parenchyma and secondary brain injury resulting from strong neuroinflammatory responses to blood components. Production of prostaglandin E2 (PGE2 is significantly upregulated following ICH and contributes to this inflammatory response in part through its E prostanoid receptor subtype 2 (EP2. Signaling through the EP2 receptor has been shown to affect outcomes of many acute and chronic neurological disorders; although, not yet explored in the context of ICH. Wildtype (WT and EP2 receptor knockout (EP2−/− mice were subjected to ICH, and various anatomical and functional outcomes were assessed by histology and neurobehavioral testing, respectively. When compared with age-matched WT controls, EP2−/− mice had 41.9 ± 4.7% smaller ICH-induced brain lesions and displayed significantly less ipsilateral hemispheric enlargement and incidence of intraventricular hemorrhage. Anatomical outcomes correlated with improved functional recovery as identified by neurological deficit scoring. Histological staining was performed to begin investigating the mechanisms involved in EP2-mediated neurotoxicity after ICH. EP2−/− mice exhibited 45.5 ± 5.8% and 41.4 ± 8.1% less blood and ferric iron accumulation, respectively. Furthermore, significantly less striatal and cortical microgliosis, striatal and cortical astrogliosis, blood–brain barrier breakdown, and peripheral neutrophil infiltration were seen in EP2−/− mice. This study is the first to suggest a deleterious role for the PGE2-EP2 signaling axis in modulating brain injury, inflammation, and functional recovery following ICH. Targeting the EP2 G protein-coupled receptor may represent a new therapeutic avenue for the treatment of hemorrhagic stroke.

  15. l-Citrulline ameliorates cerebral blood flow during cortical spreading depression in rats: Involvement of nitric oxide- and prostanoids-mediated pathway

    Directory of Open Access Journals (Sweden)

    Yuki Kurauchi

    2017-03-01

    Full Text Available l-Citrulline is a potent precursor of l-arginine, and exerts beneficial effect on cardiovascular system via nitric oxide (NO production. Migraine is one of the most popular neurovascular disorder, and imbalance of cerebral blood flow (CBF observed in cortical spreading depression (CSD contributes to the mechanism of migraine aura. Here, we investigated the effect of l-citrulline on cardiovascular changes to KCl-induced CSD. in rats. Intravenous injection of l-citrulline prevented the decrease in CBF, monitored by laser Doppler flowmetry, without affecting mean arterial pressure and heart rate during CSD. Moreover, l-citrulline attenuated propagation velocity of CSD induced by KCl. The effect of l-citrulline on CBF change was prevented by l-NAME, an inhibitor of NO synthase, but not by indomethacin, an inhibitor of cyclooxygenase. On the other hand, attenuation effect of l-citrulline on CSD propagation velocity was prevented not only by l-NAME but also by indomethacin. In addition, propagation velocity of CSD was attenuated by intravenous injection of NOR3, a NO donor, which was diminished by ODQ, an inhibitor of soluble guanylyl cyclase. These results suggest that NO/cyclic GMP- and prostanoids-mediated pathway differently contribute to the effect of l-citrulline on the maintenance of CBF.

  16. The Structure of the Heavy Calcium Isotopes and the Effective Interaction in the sd-fp Shell

    CERN Multimedia

    Dorvaux, O; Nowacki, F; Courtin, S; Marechal, F; Siiskonen, T M; Perrot, F; Pietri, S B

    2002-01-01

    Nuclei with 40 $<$ A $<$ 56, near the stability line, are very well described in the frame of the shell model. However, when the number of neutrons increases, the situation becomes more complex which explains why the interaction can be found very dissimilar within different calculations. Heavy Ca isotopes, because of the simplicity of their wave-functions, correspond to the optimal choice to fix unambiguously the interaction in this mass region.\\\\ It is proposed to measure the $\\beta$-decay of $^{51, 52, 53}$K with the help of an utmost performing neutron (TONNERRE array) and $\\gamma$- (Miniball clusters) detection, allowing efficient coincidence measurements. This will allow the lowest lying Gamow-Teller states to be located in $^{51, 52, 53}$Ca, and the still unknown properties of natural parity states to be investigated. The awaited results should allow to settle the n-n interaction in the fp shell and the Gnp matrix accross the sd and fp shells, one step farther from stability, by comparison with fu...

  17. Evaluating a LARC Expansion Program in 14 Sub-Saharan African Countries: A Service Delivery Model for Meeting FP2020 Goals.

    Science.gov (United States)

    Ngo, Thoai D; Nuccio, Olivia; Pereira, Shreya K; Footman, Katharine; Reiss, Kate

    2017-09-01

    Objectives In many sub-Saharan African countries, the use of long-acting reversible contraceptives (LARCs) is low while unmet need for family planning (FP) remains high. We evaluated the effectiveness of a LARC access expansion initiative in reaching young, less educated, poor, and rural women. Methods Starting in 2008, Marie Stopes International (MSI) has implemented a cross-country expansion intervention to increase access to LARCs through static clinics, mobile outreach units, and social franchising of private sector providers. We analyzed routine service statistics for 2008-2014 and 2014 client exit interview data. Indicators of effectiveness were the number of LARCs provided and the percentages of LARC clients who had not used a modern contraceptive in the last 3 months ("adopters"); switched from a short-term contraceptive to a LARC ("switchers"); were aged <25; lived in extreme poverty; had not completed primary school; lived in rural areas; and reported satisfaction with their overall experience at the facility/site. Results Our annual LARC service distribution increased 1037 % (from 149,881 to over 1.7 million) over 2008-2014. Of 3816 LARC clients interviewed, 46 % were adopters and 46 % switchers; 37 % were aged 15-24, 42 % had not completed primary education, and 56 % lived in a rural location. Satisfaction with services received was rated 4.46 out of 5. Conclusions The effectiveness of the LARC expansion in these 14 sub-Saharan African FP programs demonstrates vast untapped potential for wider use of LARC methods, and suggests that this service delivery model is a plausible way to support FP 2020 goals of reaching those with an unmet need for FP.

  18. Evaluating item endorsement rates for the MMPI-2-RF F-r and Fp-r scales across ethnic, gender, and diagnostic groups with a forensic inpatient sample.

    Science.gov (United States)

    Glassmire, David M; Jhawar, Amandeep; Burchett, Danielle; Tarescavage, Anthony M

    2017-05-01

    The Minnesota Multiphasic Personality Inventory-2 (MMPI-2) F(p) (Infrequency-Psychopathology) scale was developed to measure overreporting in a manner that was minimally confounded by genuine psychopathology, which was a problem with using the MMPI-2 F (Infrequency) scale among patients with severe mental illness. Although revised versions of both of these scales are included on the MMPI-2-Restructured Form and used in a forensic context, no item-level research has been conducted on their sensitivity to genuine psychopathology among forensic psychiatric inpatients. Therefore, we examined the psychometric properties of the scales in a sample of 438 criminally committed forensic psychiatric inpatients who were adjudicated as not guilty by reason of insanity and had no known incentive to overreport. We found that 20 of the 21 Fp-r items (95.2%) demonstrated endorsement rates ≤ 20%, with 14 of the items (66.7%) endorsed by less than 10% of the sample. Similar findings were observed across genders and across patients with mood and psychotic disorders. The one item endorsed by more than 20% of the sample had a 23.7% overall endorsement rate and significantly different endorsement rates across ethnic groups, with the highest endorsements occurring among Hispanic/Latino (43.3% endorsement rate) patients. Endorsement rates of F-r items were generally higher than for Fp-r items. At the scale level, we also examined correlations with the Restructured Clinical Scales and found that Fp-r demonstrated lower correlations than F-r, indicating that Fp-r is less associated with a broad range of psychopathology. Finally, we found that Fp-r demonstrated slightly higher specificity values than F-r at all T score cutoffs. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. Vitamin C Deficiency Reduces Muscarinic Receptor Coronary Artery Vasoconstriction and Plasma Tetrahydrobiopterin Concentration in Guinea Pigs

    Directory of Open Access Journals (Sweden)

    Gry Freja Skovsted

    2017-07-01

    Full Text Available Vitamin C (vitC deficiency is associated with increased cardiovascular disease risk, but its specific interplay with arteriolar function is unclear. This study investigates the effect of vitC deficiency in guinea pigs on plasma biopterin status and the vasomotor responses in coronary arteries exposed to vasoconstrictor/-dilator agents. Dunkin Hartley female guinea pigs (n = 32 were randomized to high (1500 mg/kg diet or low (0 to 50 mg/kg diet vitC for 10–12 weeks. At euthanasia, coronary artery segments were dissected and mounted in a wire-myograph. Vasomotor responses to potassium, carbachol, sodium nitroprusside (SNP, U46619, sarafotoxin 6c (S6c and endothelin-1 (ET-1 were recorded. Plasma vitC and tetrahydrobiopterin were measured by HPLC. Plasma vitC status reflected the diets with deficient animals displaying reduced tetrahydrobiopterin. Vasoconstrictor responses to carbachol were significantly decreased in vitC deficient coronary arteries independent of their general vasoconstrictor/vasodilator capacity (p < 0.001. Moreover, in vitC deficient animals, carbachol-induced vasodilator responses correlated with coronary artery diameter (p < 0.001. Inhibition of cyclooxygenases with indomethacin increased carbachol-induced vasoconstriction, suggesting an augmented carbachol-induced release of vasodilator prostanoids. Atropine abolished carbachol-induced vasomotion, supporting a specific muscarinic receptor effect. Arterial responses to SNP, potassium, S6c, U46619 and ET-1 were unaffected by vitC status. The study shows that vitC deficiency decreases tetrahydrobiopterin concentrations and muscarinic receptor mediated contraction in coronary arteries. This attenuated vasoconstrictor response may be linked to altered production of vasoactive arachidonic acid metabolites and reduced muscarinic receptor expression/signaling.

  20. Sensitization of (colon) cancer cells to death receptor related therapies A report from the FP6-ONCODEATH research consortium

    Czech Academy of Sciences Publication Activity Database

    Pintzas, A.; Zhivotovsky, B.; Workman, P.; Clarke, P.A.; Linardopoulos, S.; Martinou, J.C.; Lacal, J.C.; Robine, S.; Nasioulas, G.; Anděra, Ladislav

    2012-01-01

    Roč. 13, č. 7 (2012), s. 458-466 ISSN 1538-4047 Grant - others:EK(XE) LSHC-CT-2006-037278 Institutional support: RVO:68378050 Keywords : cancer * death receptors * kinase inhibitors * mitochondria * targeted therapies Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.287, year: 2012

  1. Differential Diagnosis of Patients with Inconclusive Parkinsonian Features Using [{sup 18}F]FP-CIT PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eunkyung; Hwang, Yu Mi; Lee, Channyoung; Oh, Sun Young; Kim, Young Chul; Choe, Jae Gol; Park, Kun Woo [Korea Univ., Seoul (Korea, Republic of); Kim, Sujin [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    It is often difficult to differentiate parkinsonism, especially when patients show uncertain parkinsonian features. We investigated the usefulness of dopamine transporter (DAT) imaging for the differential diagnosis of inconclusive parkinsonism using [{sup 18}F]FP-CIT PET. Twenty-four patients with inconclusive parkinsonian features at initial clinical evaluation and nine healthy controls were studied. Patients consisted of three subgroups: nine patients whose diagnoses were unclear concerning whether they had idiopathic Parkinson's disease or drug-induced parkinsonism ('PD/DIP'), nine patients who fulfilled neither the diagnostic criteria of PD nor of essential tremor ('PD/ET'), and six patients who were alleged to have either PD or atypical parkinsonian syndrome ('PD/APS'). Brain PET images were obtained 120 min after injection of 185 MBq [{sup 18}F]FP-CIT. Imaging results were quantified and compared with follow-up clinical diagnoses. Overall, 11 of 24 patients demonstrated abnormally decreased DAT availability on the PET scans, whereas 13 were normal. PET results could diagnose PD/DIP and PD/ET patients as having PD in six patients, DIP in seven, and ET in five; however, the diagnoses of all six PD/APS patients remained inconclusive. Among 15 patients who obtained a final follow-up diagnosis, the image-based diagnosis was congruent with the follow-up diagnosis in 11 patients. Four unsolved cases had normal DAT availability, but clinically progressed to PD during the follow-up period. [{sup 18}F]FP-CIT PET imaging is useful in the differential diagnosis of patients with inconclusive parkinsonian features, except in patients who show atypical features or who eventually progress to PD.

  2. Gas Time-of-Flight Cherenkov Detector with Radiofrequency Phototube for FP420

    International Nuclear Information System (INIS)

    Margaryan, A.

    2011-01-01

    In this paper, the gas Cherenkov detector with radiofrequency phototube is considered as a fast-timing detector for FP420 project. The detector serves for precise Time-of-Flight measurements of forward going protons, capable of accurate vertex reconstruction and background rejection at high luminosities. The proposed technique is a high resolution (∼ 5 ps FWHM for a single proton), high rate (∼ MHz) and highly stable (less than 1 ps) timing technique capable to detect up to several tens events in a short (∼ 1 ns) time interval. (author)

  3. Sustained Release of Prostaglandin E2 in Fibroblasts Expressing Ectopically Cyclooxygenase 2 Impairs P2Y-Dependent Ca2+-Mobilization

    Directory of Open Access Journals (Sweden)

    María Pimentel-Santillana

    2014-01-01

    Full Text Available The nucleotide uridine trisphosphate (UTP released to the extracellular milieu acts as a signaling molecule via activation of specific pyrimidine receptors (P2Y. P2Y receptors are G protein-coupled receptors expressed in many cell types. These receptors mediate several cell responses and they are involved in intracellular calcium mobilization. We investigated the role of the prostanoid PGE2 in P2Y signaling in mouse embryonic fibroblasts (MEFs, since these cells are involved in different ontogenic and physiopathological processes, among them is tissue repair following proinflammatory activation. Interestingly, Ca2+-mobilization induced by UTP-dependent P2Y activation was reduced by PGE2 when this prostanoid was produced by MEFs transfected with COX-2 or when PGE2 was added exogenously to the culture medium. This Ca2+-mobilization was important for the activation of different metabolic pathways in fibroblasts. Moreover, inhibition of COX-2 with selective coxibs prevented UTP-dependent P2Y activation in these cells. The inhibition of P2Y responses by PGE2 involves the activation of PKCs and PKD, a response that can be suppressed after pharmacological inhibition of these protein kinases. In addition to this, PGE2 reduces the fibroblast migration induced by P2Y-agonists such as UTP. Taken together, these data demonstrate that PGE2 is involved in the regulation of P2Y signaling in these cells.

  4. [123I]FP-CIT (DaTSCAN) and SPET in the diagnostics of Parkinson's disease and Parkinsonian syndromes

    International Nuclear Information System (INIS)

    Chmielowski, K.; Szalus, B.; Pietrzykowski, J.; Brodacki, B.; Kotowicz, J.; Skrobowska, E.

    2003-01-01

    The aim of study was to verify the diagnostic value of the radiopharmaceutic [ 123I ]FP-CIT (DaTSCAN) in functional imaging of the presynaptical dopaminergic system in patients with Parkison's disease and parkinsonian syndromes: multiple system atrophy, orthostatic hypotonia Shy-Drager, essential tremor. That pilot study group consisted of 8 patients in which either preliminary diagnosis or suspicion of Parkinson's disease, parkinsonian syndrome or multiple system atrophy was set. Imaging of the brain with SPET (dual head detector Varicam Elscint) and MRI were performed. The radiopharmaceutic [ 123I ] FP-CIT (DaTSCAN) was administered intravenously in the dose 145 -148 MBq. SPET images were reconstructed by filtered backprojection with the use of Butterworth filter. The images were inspected visually. Images from SPET and MRI were superimposed by means of the workstation Hermes (Nucklear Diagnostic) with designatad regions interest (ROI) in the striatum and occipital cortex in order to assess semiquantitatively the binding of dopamine transporter. In the group of 8 patients evaluated with the use of [ 123I ]FP-CIT DaTSCAN four had normal results, and four - abnormal. The preliminary diagnosis was sustained in 3/8 of patients (including Parkinson's disease in two patients and multiple system atrophy in one patient). In the remainig 5 patients the preliminary diagnosis was changed, namely: in 2 cases the essential tremor was diagnosed, in 1 case - Parkinson's disease, in 1 case - orthostaic Sky-Drager, and in 1 case - despite the tremor of the upper limbs - results were normal. In all 8 patients the tracer proved to be useful in the confirmation of clinical diagnosis, especially in the differentiation between the essential tremor and Parkinson's disease. In the case of multiple system atrophy the imaging revealed significant loss of nigrostriatal dopaminergic neurons. Such loss was observed also in the cases of Parkinson's disease affecting the posterior parts of the

  5. The Challenges Associated with Accounting for the Army's Force Provider (FP) System when Deployed in Support of Military Operations

    National Research Council Canada - National Science Library

    Correia, Carlos A; Horner, Allen; McLaughlin, James; Stewardson, Donald

    2008-01-01

    .... The analysis will address the inherent challenges associated with accountability of the FP System when deployed and decommissioned to undergo RESET, the lack of a singular management and decision...

  6. Repeated administration of D-amphetamine induces loss of [{sup 123}I]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study

    Energy Technology Data Exchange (ETDEWEB)

    Booij, Jan [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands)]. E-mail: j.booij@amc.uva.nl; Bruin, Kora de [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands); Gunning, W. Boudewijn [Department of Neurology, Epilepsy Centre Kempenhaeghe, 5590 AB Heeze (Netherlands)

    2006-04-15

    In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in amphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of D-AMPH or methamphetamine (METH) may induce loss of binding to striatal DATs in rats by using an experimental biodistribution study design and a SPECT tracer for the DAT ([{sup 123}I]FP-CIT). Methods: Groups of male rats (n=10 per group) were treated with D-AMPH (10 mg/kg body weight), METH (10 mg/kg body weight), or saline, twice a day for 5 consecutive days. Five days later, [{sup 123}I]FP-CIT was injected intravenously, and 2 h later, the rats were sacrificed and radioactivity was assayed. Results: In D-AMPH but not METH-treated rats, striatal [{sup 123}I]FP-CIT uptake was significantly lower (approximately 17%) than in the control group. Conclusion: These data show that [{sup 123}I]FP-CIT can be used to detect AMPH-induced changes in DAT binding and may validate the use of DAT radiotracers to study AMPH-induced changes in striatal DAT binding in vivo.

  7. Inverse agonism of SQ 29,548 and Ramatroban on Thromboxane A2 receptor.

    Directory of Open Access Journals (Sweden)

    Raja Chakraborty

    Full Text Available G protein-coupled receptors (GPCRs show some level of basal activity even in the absence of an agonist, a phenomenon referred to as constitutive activity. Such constitutive activity in GPCRs is known to have important pathophysiological roles in human disease. The thromboxane A2 receptor (TP is a GPCR that promotes thrombosis in response to binding of the prostanoid, thromboxane A2. TP dysfunction is widely implicated in pathophysiological conditions such as bleeding disorders, hypertension and cardiovascular disease. Recently, we reported the characterization of a few constitutively active mutants (CAMs in TP, including a genetic variant A160T. Using these CAMs as reporters, we now test the inverse agonist properties of known antagonists of TP, SQ 29,548, Ramatroban, L-670596 and Diclofenac, in HEK293T cells. Interestingly, SQ 29,548 reduced the basal activity of both, WT-TP and the CAMs while Ramatroban was able to reduce the basal activity of only the CAMs. Diclofenac and L-670596 showed no statistically significant reduction in basal activity of WT-TP or CAMs. To investigate the role of these compounds on human platelet function, we tested their effects on human megakaryocyte based system for platelet activation. Both SQ 29,548 and Ramatroban reduced the platelet hyperactivity of the A160T genetic variant. Taken together, our results suggest that SQ 29,548 and Ramatroban are inverse agonists for TP, whereas, L-670596 and Diclofenac are neutral antagonists. Our findings have important therapeutic applications in the treatment of TP mediated pathophysiological conditions.

  8. Emerging migraine treatments and drug targets

    DEFF Research Database (Denmark)

    Olesen, Jes; Ashina, Messoud

    2011-01-01

    Migraine has a 1-year prevalence of 10% and high socioeconomic costs. Despite recent drug developments, there is a huge unmet need for better pharmacotherapy. In this review we discuss promising anti-migraine strategies such as calcitonin gene-related peptide (CGRP) receptor antagonists and 5....... Tonabersat, a cortical spreading depression inhibitor, has shown efficacy in the prophylaxis of migraine with aura. Several new drug targets such as nitric oxide synthase, the 5-HT(1D) receptor, the prostanoid receptors EP(2) and EP(4), and the pituitary adenylate cyclase receptor PAC1 await development....... The greatest need is for new prophylactic drugs, and it seems likely that such compounds will be developed in the coming decade....

  9. Decreased striatal dopamine transporter binding assessed with [123I] FP-CIT in first-episode schizophrenic patients with and without short-term antipsychotic-induced parkinsonism.

    Science.gov (United States)

    Mateos, Jose J; Lomeña, Francisco; Parellada, Eduardo; Font, Mireia; Fernandez, Emili; Pavia, Javier; Prats, Alberto; Pons, Francisca; Bernardo, Miquel

    2005-09-01

    Drug-induced parkinsonism (DIP) is one of the main causes of treatment drop-out in schizophrenic patients causing a high incidence of relapse that leads patients to a bad clinical prognosis. The dopaminergic nigrostriatal pathway is involved in the movement control, so the study of the dopamine transporter (DAT) could be of great value to determine its implication in the appearance of DIP. The goal of the study is to determine the striatal DAT binding assessed with [(123)I] FP-CIT SPECT in first-episode neuroleptic-naive schizophrenic in-patients with DIP after short-term antipsychotic treatment. The [(123)I] FP-CIT binding ratios of ten schizophrenic in-patients who developed DIP during the first 4-week period of risperidone treatment (6+/-2 mg/day) were compared with ten schizophrenic in-patients treated with the same doses of risperidone and who do not developed DIP and with ten age-matched healthy subjects. Quantitative analyses of SPECTs were performed using regions of interest located in caudate, putamen and occipital cortex. Parkinsonism was assessed by the Simpson-Angus Scale and the psychopathological status by the Clinical General Impression and Positive and Negative Syndrome Scales. Whole striatal [(123)I] FP-CIT binding ratios were significantly lower in patients with and without DIP than in healthy subjects (p<0.001). This was also observed in whole putamen (p<0.001) and caudate nucleus (p<0.001). Females showed higher whole striatal [(123)I] FP-CIT binding ratios than males (p<0.05). No differences in psychopathological scales were observed between patients with and without DIP. Our first-episode schizophrenic patients with and without DIP after short-term risperidone treatment have a decreased striatal DAT binding assessed with [(123)I] FP-CIT. This alteration could be related to the schizophrenic disease or may be secondary to the antipsychotic treatment.

  10. The potential value of a pictorial atlas for aid in the visual diagnosis of 123I FP-CIT SPECT scans

    International Nuclear Information System (INIS)

    Goethals, I.; Ham, H.; Dobbeleir, A.; D'Asseler, Y.; Santens, P.

    2009-01-01

    The aim of our study was to evaluate the value of a pictorial atlas of 123 I FP-CIT SPECT images for aid in the visual diagnosis. Patients, materials, methods: Sixty patients, of whom 20 were clinically diagnosed as 'non-parkinsonian' and 40 as having Parkinson's disease or any related disorder, were included in the study. An atlas consisting of 12 123 I FP-CIT SPECT images was constructed first. Validity of the atlas was investigated by performing a receiver operating characteristic (ROC) analysis with the clinical diagnosis as the gold standard. The remaining 48 SPECT images were visually assessed twice by 5 observers, first with and secondly without consulting the atlas, or vice versa. The added value of the atlas was investigated by comparing the diagnostic accuracy and the interobserver variability for both methods. Results: ROC analysis performed on the atlas yielded an area under the curve of 1 for a threshold discriminating between clinically non-parkinsonian and parkinsonian patients that was situated between image 4 and 5 of the atlas, For the diagnostic accuracy, we found that the area under the ROC curve was systematically higher if observers had access to the atlas compared to when they had not (Wilcoxon's test, p 123 I FP-CIT SPECT scans. (orig.)

  11. A maladaptive role for EP4 receptors in mouse mesangial cells.

    Directory of Open Access Journals (Sweden)

    Guang-xia Yang

    Full Text Available Roles of the prostaglandin E2 E-prostanoid 4 receptor (EP4 on extracellular matrix (ECM accumulation induced by TGF-β1 in mouse glomerular mesangial cells (GMCs remain unknown. Previously, we have identified that TGF-β1 stimulates the expression of FN and Col I in mouse GMCs. Here we asked whether stimulation of EP4 receptors would exacerbate renal fibrosis associated with enhanced glomerular ECM accumulation. We generated EP4(Flox/Flox and EP4(+/- mice, cultured primary WT, EP4(Flox/Flox and EP4(+/- GMCs, AD-EP4 transfected WT GMCs (EP4 overexpression and AD-Cre transfected EP4(Flox/Flox GMCs (EP4 deleted. We found that TGF-β1-induced cAMP and PGE2 synthesis decreased in EP4 deleted GMCs and increased in EP4 overexpressed GMCs. Elevated EP4 expression in GMCs augmented the coupling of TGF-β1 to FN, Col I expression and COX2/PGE2 signaling, while TGF-β1 induced FN, Col I expression and COX2/PGE2 signaling were down-regulated in EP4 deficiency GMCs. 8 weeks after 5/6 nephrectomy (Nx, WT and EP4(+/- mice exhibited markedly increased accumulation of ECM compared with sham-operated controls. Albuminuria, blood urea nitrogen and creatinine (BUN and Cr concentrations were significantly increased in WT mice as compared to those of EP4(+/- mice. Urine osmotic pressure was dramatically decreased after 5/6 Nx surgery in WT mice as compared to EP4(+/- mice. The pathological changes in kidney of EP4(+/- mice was markedly alleviated compared with WT mice. Immunohistochemical analysis showed significant reductions of Col I and FN in the kidney of EP4(+/- mice compared with WT mice. Collectively, this investigation established EP4 as a potent mediator of the pro-TGF-β1 activities elicited by COX2/PGE2 in mice GMCs. Our findings suggested that prostaglandin E2, acting via EP4 receptors contributed to accumulation of ECM in GMCs and promoted renal fibrosis.

  12. Assessment of core damage models in SCDAP/RELAP5 during OECD LOFT LP-FP-2

    International Nuclear Information System (INIS)

    Coryell, E.W.

    1991-01-01

    The US Nuclear Regulatory Commission has sponsored a program to apply the SCDAP/RELAP5 code to analysis of the transient and reflood phases of the OECD LOFT LP-FP-2 Experiment. The principal objectives of the LP-FP-2 experiment were to determine the fission product release from the fuel during the early phases of a severe fuel damage scenario and to examine the phenomena controlling fission product transport in a vapor/aerosol environment. Calculations with the SCDAP/RELAP5 code, developed at the INEL with NRC support, have been performed to (1) examine the phenomena controlling the progression of both transient and reflood phases of the experiment, (2) enhance our understanding of the phenomena occurring during reflood and add credence to the postulated phenomenological sequence, (3) assess the ability of SCDAP/RELAP5 to examine severe fuel damage issues and phenomena, and (4) identify code strengths and deficiencies with the intent of prioritizing code improvements. Results indicate that the code is able to analyze the early phases of severe fuel damage reasonably well, with potential deficiencies in modelling interaction between molten control rod material and intact fuel

  13. Biodiversity monitoring in Europe: the EU FP7 EBONE project. European biodiversity observation NEtwork

    CSIR Research Space (South Africa)

    Lück-Vogel, Melanie

    2008-09-01

    Full Text Available submission Presentation Poster presentation A) Title Biodiversity Monitoring in Europe: The EU FP7 EBONE project European Biodiversity Observation NEtwork B) Short title EBONE - European Biodiversity Observation NEtwork C) Author(s) Vogel, M. (1... stream_source_info Vogel_2008.pdf.txt stream_content_type text/plain stream_size 3055 Content-Encoding UTF-8 stream_name Vogel_2008.pdf.txt Content-Type text/plain; charset=UTF-8 BIOTA AFRICA Congress 2008 Abstract...

  14. fp shell spectroscopy: numerical calculations and theoretical aspects

    International Nuclear Information System (INIS)

    Pasquini, E.A.

    1976-01-01

    The fp shell spectroscopy is reviewed and the fsup(n) model is introduced. It is shown that the two-body Hamiltonian monopolar terms play a very important part in the behavior of these spectra, and that realistic interactions do not reproduce them. The detailed study of the following nuclei was undertaken: 47 Ca, 48 Ca, 49 Ca, 56 Ni, 48 Sc, 50 Sc, 50 Ti, 46 Ti, 50 Cr, 47 V and 49 Cr. It is shown that very precise values of the few parameters defining the monopolar contributions could be extracted from the comparison between calculations and experimental data. The study of the binding energies of all the nuclei from 40 Ca to 56 Ni shows that it is necessary to introduce three-body forces. The results also reveal the effect of nondiagonal multipoles which are well reproduced by realistic interactions. A better understanding of the electromagnetic behavior of the fsup(n) nuclei of their conjugaison properties and of the relation between 42 Sc and 48 Sc was obtained. Several calculations of two-body transfer amplitudes were proposed [fr

  15. Alpha particle cluster states in (fp)-shell nuclei

    International Nuclear Information System (INIS)

    Merchant, A.C.

    1987-07-01

    Alpha particle cluster structure is known experimentally to persist throughout the mass range 16 ≤ A ≤ 20, and has been very successfully described in this region in terms of the Buck-Dover-Vary local potential cluster model. It is argued that an analogous cluster structure should be present in nuclei at the beginning of the (fp) - shell, and the available experimental data are examined to determine likely alpha particle cluster state candidates in the mass range 40 ≤ A ≤ 44. Calculations of the cluster state spectra and mean square cluster-core separation distances (which may be readily used to evaluate E2 electromagnetic transition rates) for sup(40)Ca, sup(42)Ca, sup(42)Sc, sup(43)Sc, sup(43)Ti and sup(44)Ti using the above mentioned model are presented, and compared with experimental measurements where possible. The agreement between theory and experiment is generally good (although inferior to that obtained in the (sd)-shell) and points to the desirability of an extension and improvement of the measurements of the properties of the excited states in these nuclei. (author)

  16. Thermonuclear 19F(p, {{\\boldsymbol{\\alpha }}}_{0})16O reaction rate

    Science.gov (United States)

    He, Jian-Jun; Lombardo, Ivano; Dell'Aquila, Daniele; Xu, Yi; Zhang, Li-Yong; Liu, Wei-Ping

    2018-01-01

    The thermonuclear 19F(p, {{{α }}}0)16O reaction rate in the temperature region 0.007-10 GK has been derived by re-evaluating the available experimental data, together with the low-energy theoretical R-matrix extrapolations. Our new rate deviates by up to about 30% compared to the previous results, although all rates are consistent within the uncertainties. At very low temperature (e.g. 0.01 GK) our reaction rate is about 20% lower than the most recently published rate, because of a difference in the low energy extrapolated S-factor and a more accurate estimate of the reduced mass used in the calculation of the reaction rate. At temperatures above ˜1 GK, our rate is lower, for instance, by about 20% around 1.75 GK, because we have re-evaluated the previous data (Isoya et al., Nucl. Phys. 7, 116 (1958)) in a meticulous way. The present interpretation is supported by the direct experimental data. The uncertainties of the present evaluated rate are estimated to be about 20% in the temperature region below 0.2 GK, and are mainly caused by the lack of low-energy experimental data and the large uncertainties in the existing data. Asymptotic giant branch (AGB) stars evolve at temperatures below 0.2 GK, where the 19F(p, {{α }})16O reaction may play a very important role. However, the current accuracy of the reaction rate is insufficient to help to describe, in a careful way, the fluorine over-abundances observed in AGB stars. Precise cross section (or S factor) data in the low energy region are therefore needed for astrophysical nucleosynthesis studies. Supported by National Natural Science Foundation of China (11490562, 11490560, 11675229) and National Key Research and Development Program of China (2016YFA0400503)

  17. Scientific Opinion on the Pest Risk Analysis on Phytophthora ramorum prepared by the FP6 project RAPRA

    DEFF Research Database (Denmark)

    Baker, R.; Candresse, T.; Dormannsné Simon, E.

    2011-01-01

    The Panel on Plant Health was asked to deliver a scientific opinion on the Pest Risk Analysis on Phytophthora ramorum prepared by the FP6 project RAPRA, taking into account comments by Member States and additional information since RAPRA. P. ramorum is the oomycete causing sudden oak death...

  18. Dopaminergic dysfunction and psychiatric symptoms in movement disorders: a 123I-FP-CIT SPECT study

    International Nuclear Information System (INIS)

    Di Giuda, Daniela; Cocciolillo, Fabrizio; Bruno, Isabella; Giordano, Alessandro; Camardese, Giovanni; Pucci, Lorella; Janiri, Luigi; Bentivoglio, Anna Rita; Guidubaldi, Arianna; Fasano, Alfonso

    2012-01-01

    Psychiatric symptoms frequently occur in patients with movement disorders. They are not a mere reaction to chronic disability, but most likely due to a combination of psychosocial factors and biochemical dysfunction underlying the movement disorder. We assessed dopamine transporter (DAT) availability by means of 123 I-FP-CIT SPECT, and motor and psychiatric features in patients with Parkinson's disease, primary dystonia and essential tremor, exploring the association between SPECT findings and symptom severity. Enrolled in the study were 21 patients with Parkinson's disease, 14 patients with primary dystonia and 15 patients with essential tremor. The severity of depression symptoms was assessed using the Hamilton depression rating scale, anxiety levels using the Hamilton anxiety rating scale and hedonic tone impairment using the Snaith-Hamilton pleasure scale. Specific 123 I-FP-CIT binding in the caudate and putamen was calculated based on ROI analysis. The control group included 17 healthy subjects. As expected, DAT availability was significantly decreased in patients with Parkinson's disease, whereas in essential tremor and dystonia patients it did not differ from that observed in the control group. In Parkinson's disease patients, an inverse correlation between severity of depression symptoms and DAT availability in the left caudate was found (r = -0.63, p = 0.002). In essential tremor patients, levels of anxiety symptoms were inversely correlated with DAT availability in the left caudate (r = -0.69, p = 0.004). In dystonia patients, the severities of both anxiety and depression symptoms were inversely associated with DAT availability in the left putamen (r = -0.71, p = 0.004, and r = -0.75, p = 0.002, respectively). There were no correlations between psychometric scores and 123 I-FP-CIT uptake ratios in healthy subjects. We found association between presynaptic dopaminergic function and affective symptoms in different movement disorders. Interestingly, the

  19. Calibration of gamma camera systems for a multicentre European ¹²³I-FP-CIT SPECT normal database

    DEFF Research Database (Denmark)

    Tossici-Bolt, Livia; Dickson, John C; Sera, Terez

    2011-01-01

    A joint initiative of the European Association of Nuclear Medicine (EANM) Neuroimaging Committee and EANM Research Ltd. aimed to generate a European database of [(123)I]FP-CIT single photon emission computed tomography (SPECT) scans of healthy controls. This study describes the characterization...

  20. Geometrical (Degree 0 Modelling of a FP3+3×RTR+MP3 Type Parallel Topology Robotic Guiding Device, Using the „Pair of Frames” (PF Concept

    Directory of Open Access Journals (Sweden)

    Calin Miclosina

    2005-01-01

    Full Text Available The geometrical (degree 0 model of a parallel topology robotic guiding device represents the position-orientation matrix of the mobile platform (MP versus the fixed one (FP; this model refers to generalized displacements. The kinematical scheme of a FP3+3×RTR+MP3 type mechanism is presented, as well as the manner of choice of the attached pair of frames (PF to the links. In the case of direct geometrical modelling, for certain displacements of the actuated translational joints, the position-orientation matrix of the mobile platform versus the fixed one is determined. For inverse geometrical modelling, the position-orientation matrix of MP versus FP is known and the displacements of the actuated translational joints are determined.

  1. Effects of anesthetics on vesicular monoamine transporter type 2 binding to 18F-FP-(+)-DTBZ: a biodistribution study in rat brain

    International Nuclear Information System (INIS)

    Chen, Zhengping; Tang, Jie; Liu, Chunyi; Li, Xiaomin; Huang, Hongbo; Xu, Xijie; Yu, Huixin

    2016-01-01

    Objectives: The in vivo binding analysis of vesicular monoamine transporter type 2 (VMAT2) to radioligand has provided a means of investigating related disorders. Anesthesia is often inevitable when the investigations are performed in animals. In the present study, we tested effects of four commonly-used anesthetics: isoflurane, pentobarbital, chloral hydrate and ketamine, on in vivo VMAT2 binding to 18 F-FP-(+)-DTBZ, a specific VMAT2 radioligand, in rat brain. Methods: The transient equilibrium time window for in vivo binding of 18 F-FP-(+)-DTBZ after a bolus injection was firstly determined. The brain biodistribution studies under anesthetized and awake rats were then performed at the equilibrium time. Standard uptake values (SUVs) of the interest brain regions: the striatum (ST), hippocampus (HP), cortex (CX) and cerebellum (CB) were obtained; and ratios of tissue to cerebellum were calculated. Results: Isoflurane and pentobarbital did not alter distribution of 18 F-FP-(+)-DTBZ in the brain relative to the awake group; neither SUVs nor ratios of ST/CB and HP/CB were altered significantly. Chloral hydrate significantly increased SUVs of all the brain regions, but did not significantly alter ratios of ST/CB and HP/CB. Ketamine significantly increased SUVs of the striatum, hippocampus and cortex, and insignificantly increased the SUV of the cerebellum; consequently, ketamine significantly increased ratios of ST/CB and HP/CB. Conclusions: It is concluded that in vivo VMAT2 binding to 18 F-FP-(+)-DTBZ are not altered by isoflurane and pentobarbital, but altered by chloral hydrate and ketamine. Isoflurane and pentobarbital may be promising anesthetic compounds for investigating in vivo VMAT2 binding. Further studies are warranted to investigate the interactions of anesthetics with VMAT2 binding potential with in vivo PET studies.

  2. Overview of the Main Achievements of the FP7 EURATOM Collaborative Project ACSEPT

    International Nuclear Information System (INIS)

    Bourg, Stephane

    2013-01-01

    Conclusion: • 4 consolidated flowsheets (r-SANEX, i-SANEX, 1c-SANEX, GANEX2); • 3 hots-tests, 1 spiked test (hydro); • A huge amount of work in organic synthesis and screening (hydro); • The best candidate ligand families considered as identified (hydro); • Relevant options for exhaustive electrolysis and actinide back-extraction from aluminum identified (pyro); • Relevant options for salt purification and waste conditioning (pyro); • Progresses in head-end steps; • Outputs for other FP7 projects; • High involvement in T&E issues; • High level of dissemination

  3. {sup 123}I-FP-CIT SPECT findings and its clinical relevance in prodromal dementia with Lewy bodies

    Energy Technology Data Exchange (ETDEWEB)

    Kasanuki, Koji [Juntendo University School of Medicine, PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo (Japan); Juntendo University School of Medicine, Department of Psychiatry, Tokyo (Japan); Mayo Clinic, Department of Neuroscience, Jacksonville, FL (United States); Iseki, Eizo; Ota, Kazumi [Juntendo University School of Medicine, PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo (Japan); Juntendo University School of Medicine, Department of Psychiatry, Tokyo (Japan); Kondo, Daizo; Sato, Kiyoshi [Juntendo University School of Medicine, PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo (Japan); Ichimiya, Yosuke; Arai, Heii [Juntendo University School of Medicine, Department of Psychiatry, Tokyo (Japan)

    2017-03-15

    Evidence for the prodromal stage of dementia with Lewy bodies (DLB) is very limited. To address this issue, we investigate the {sup 123}I-FP-CIT SPECT measure of dopamine transporter binding finding and its clinical relevance. We enrolled subjects into a prodromal DLB group (PRD-DLB) (n = 20) and clinical DLB group (CLIN-DLB) (n = 18) and compared these groups with an Alzheimer's disease control group (AD) (n = 10). PRD-DLB was defined as patients having the non-motor symptoms associated with Lewy body disease (LBD) [i.e. REM sleep behavior disorder (RBD), olfactory dysfunction, autonomic dysfunction, and depression] and showing characteristic diffuse occipital hypometabolism in {sup 18}F-FDG PET. CLIN-DLB was defined as patients fulfilling the established criteria of probable DLB. Striatal specific binding ratio (SBR) of {sup 123}I-FP-CIT SPECT was used for objective group comparisons. The correlations between SBR and cognitive function (MMSE), motor symptoms (UPDRS3), and duration of LBD-associated non-motor symptoms were compared between the two DLB groups. Mean SBR scores of both PRD-DLB and CLIN-DLB were significantly lower than those of AD. No correlation was found between SBR and MMSE scores. Both in the CLIN-DLB and total DLB groups, SBR scores were negatively correlated with UPDRS3 scores, whereas no correlation was found in PRD-DLB. Among the LBD-related non-motor symptoms, duration of olfactory dysfunction, and RBD demonstrated negative correlation with SBR scores in PRD-DLB. {sup 123}I-FP-CIT SPECT may play a role for detecting DLB among the subjects in prodromal stage. During this stage, long-term olfactory dysfunction and/or RBD may indicate more severe degeneration of the nigro-striatal dopaminergic pathway. (orig.)

  4. Nicotinic acetylcholine receptor availability in cigarette smokers: effect of heavy caffeine or marijuana use.

    Science.gov (United States)

    Brody, Arthur L; Hubert, Robert; Mamoun, Michael S; Enoki, Ryutaro; Garcia, Lizette Y; Abraham, Paul; Young, Paulina; Mandelkern, Mark A

    2016-09-01

    Upregulation of α4β2* nicotinic acetylcholine receptors (nAChRs) is one of the most well-established effects of chronic cigarette smoking on the brain. Prior research by our group gave a preliminary indication that cigarette smokers with concomitant use of caffeine or marijuana have altered nAChR availability. We sought to determine if smokers with heavy caffeine or marijuana use have different levels of α4β2* nAChRs than smokers without these drug usages. One hundred and one positron emission tomography (PET) scans, using the radiotracer 2-FA (a ligand for β2*-containing nAChRs), were obtained from four groups of males: non-smokers without heavy caffeine or marijuana use, smokers without heavy caffeine or marijuana use, smokers with heavy caffeine use (mean four coffee cups per day), and smokers with heavy marijuana use (mean 22 days of use per month). Total distribution volume (Vt/fp) was determined for the brainstem, prefrontal cortex, and thalamus, as a measure of nAChR availability. A significant between-group effect was found, resulting from the heavy caffeine and marijuana groups having the highest Vt/fp values (especially for the brainstem and prefrontal cortex), followed by smokers without such use, followed by non-smokers. Direct between-group comparisons revealed significant differences for Vt/fp values between the smoker groups with and without heavy caffeine or marijuana use. Smokers with heavy caffeine or marijuana use have higher α4β2* nAChR availability than smokers without these drug usages. These findings are likely due to increased nicotine exposure but could also be due to an interaction on a cellular/molecular level.

  5. Age-related effects and gender differences in Japanese healthy controls for [123I] FP-CIT SPECT

    International Nuclear Information System (INIS)

    Yamamoto, Hideo; Arimura Shinichi; Nakanishi, Atsushi; Shimo, Yasushi; Motoi, Yumiko; Ishiguro, Koichi; Murakami, Koji; Hattori, Nobutaka; Aoki, Shigeki

    2017-01-01

    Dopamine transporter (DAT) imaging with [ 123 I]FP-CIT (DaTSCAN) is a widely used diagnostic tool for Parkinsonism and dementia. Since it was approved by the Japanese Ministry of Health, Labor, and Welfare in 2013, there have been no articles focusing on a Japanese normal population. The aim of this study was to examine the effect of aging and gender on DAT availability in Japanese people. SPECT imaging of 30 healthy Japanese controls (17 males, 13 females; range 50-86 years, mean 70 years) was performed SPECT images were reconstructed using a three-dimensional order subset expectation maximization (OSEM) algorithm with correction of the point spread function and scatter correction, without attenuation correction. The specific binding ratio (SBR) was calculated by DAT view software. Statistical analyses were performed using linear regression analysis, analysis of variance, and multiple comparison analysis. A strong correlation between the SBR and age was observed. The correlation coefficient in males and females were -0.566 and -0.502, respectively. The analysis of variance revealed that aging led to a decline of the SBR, and a significant difference (p = 0.005) was observed among generations. Gender also affected the SBR, and there was a significant difference between males and females (p = 0.036). The SBR in females was higher than in males. Consequently, the multiple comparison revealed a significant difference between 50s and 70s (p = 0.015) and 50s and 80s (p = 0.006). This is the first [ 123 I]FP-CIT SPECT study on subjects with normal dopamine function in Asian countries. This study provides a database of [ 123 I]FP-CIT SPECT in Japanese healthy controls. Higher DAT availability was found in women than in men. An average age-related decline in DAT availability of 8.9% was found in both genders. The data collected in this study would be helpful for Japanese physicians to make a differential diagnosis in Parkinsonian syndrome. The registration identification

  6. Dopaminergic dysfunction and psychiatric symptoms in movement disorders: a {sup 123}I-FP-CIT SPECT study

    Energy Technology Data Exchange (ETDEWEB)

    Di Giuda, Daniela; Cocciolillo, Fabrizio; Bruno, Isabella; Giordano, Alessandro [Universita Cattolica del Sacro Cuore, Istituto di Medicina Nucleare, Rome (Italy); Camardese, Giovanni; Pucci, Lorella; Janiri, Luigi [Universita Cattolica del Sacro Cuore, Istituto di Psichiatria e Psicologia, Rome (Italy); Bentivoglio, Anna Rita; Guidubaldi, Arianna [Universita Cattolica del Sacro Cuore, Istituto di Neurologia, Rome (Italy); Fasano, Alfonso [Universita Cattolica del Sacro Cuore, Istituto di Neurologia, Rome (Italy); AFaR-Associazione Fatebenefratelli per la Ricerca, Rome (Italy)

    2012-12-15

    Psychiatric symptoms frequently occur in patients with movement disorders. They are not a mere reaction to chronic disability, but most likely due to a combination of psychosocial factors and biochemical dysfunction underlying the movement disorder. We assessed dopamine transporter (DAT) availability by means of {sup 123}I-FP-CIT SPECT, and motor and psychiatric features in patients with Parkinson's disease, primary dystonia and essential tremor, exploring the association between SPECT findings and symptom severity. Enrolled in the study were 21 patients with Parkinson's disease, 14 patients with primary dystonia and 15 patients with essential tremor. The severity of depression symptoms was assessed using the Hamilton depression rating scale, anxiety levels using the Hamilton anxiety rating scale and hedonic tone impairment using the Snaith-Hamilton pleasure scale. Specific {sup 123}I-FP-CIT binding in the caudate and putamen was calculated based on ROI analysis. The control group included 17 healthy subjects. As expected, DAT availability was significantly decreased in patients with Parkinson's disease, whereas in essential tremor and dystonia patients it did not differ from that observed in the control group. In Parkinson's disease patients, an inverse correlation between severity of depression symptoms and DAT availability in the left caudate was found (r = -0.63, p = 0.002). In essential tremor patients, levels of anxiety symptoms were inversely correlated with DAT availability in the left caudate (r = -0.69, p = 0.004). In dystonia patients, the severities of both anxiety and depression symptoms were inversely associated with DAT availability in the left putamen (r = -0.71, p = 0.004, and r = -0.75, p = 0.002, respectively). There were no correlations between psychometric scores and {sup 123}I-FP-CIT uptake ratios in healthy subjects. We found association between presynaptic dopaminergic function and affective symptoms in different movement

  7. The effect of levodopa therapy on dopamine transporter SPECT imaging with{sup 123}I-FP-CIT in patients with Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Schillaci, Orazio; Filippi, Luca; Manni, Carlo; Danieli, Roberta; Simonetti, Giovanni [University Tor Vergata, Department of Biopathology and Diagnostic Imaging, Rome (Italy); Pierantozzi, Mariangela; Brusa, Livia; Bernardi, Giorgio; Stanzione, Paolo [University Tor Vergata, Department of Neurological Sciences, Rome (Italy); Santa Lucia Foundation I.R.C.C.S., Rome (Italy)

    2005-12-01

    The aim of this study was to evaluate, by means of {sup 123}I-FP-CIT SPECT, the effect of chronic treatment with levodopa on striatal dopamine transporter (DAT) in patients with Parkinson's disease. Fifteen patients under stable levodopa/carbidopa monotherapy were imaged twice: at baseline on medication and after at least 20 days of treatment wash-out. DAT levels were assessed from SPECT imaging for the entire striatum, the right and left striatum, the right and left putamen and the right and left caudate, as a ratio of regional brain activities using the formula: (striatal region of interest-occipital)/occipital. During levodopa wash-out, despite a worsening in patients' clinical disability (H and Y mean stage 2.53{+-}0.58 versus 1.73{+-}0.45 on therapy, p<0.001), striatal{sup 123}I-FP-CIT levels were not significantly different from those at baseline in any of the brain regions examined. The results of this study suggest that levodopa does not affect{sup 123}I-FP-CIT brain imaging and confirm that it is not necessary to withdraw this medication to measure DAT levels with SPECT. (orig.)

  8. Dopamine transporter imaging in the aged rat: a [123I]FP-CIT SPECT study

    International Nuclear Information System (INIS)

    Niñerola-Baizán, Aida; Rojas, Santiago; Roé-Vellvé, Núria; Lomeña, Francisco; Ros, Domènec

    2015-01-01

    Introduction: Rodent models are extensively used to assess the biochemical and physiological changes associated with aging. They play a major role in the development of therapies for age-related pathologies such as Parkinson's disease. To validate the usefulness of these animal models in aging or age-related disease research, the consistency of cerebral aging processes across species must be evaluated. The dopaminergic system seems particularly susceptible to the aging process. One of the results of this susceptibility is a decline in striatal dopamine transporter (DAT) availability. Methods: We sought to ascertain whether similar age changes could be detected in-vivo in rats, using molecular imaging techniques such as single photon emission computed tomography (SPECT) with [ 123 I]FP-CIT. Results: A significant decrease of 17.21% in the striatal specific uptake ratio was observed in the aged rats with respect to the young control group. Conclusions: Our findings suggest that age-related degeneration in the nigrostriatal track is similar in humans and rats, which supports the use of this animal in models to evaluate the effect of aging on the dopaminergic system. Advances in Knowledge and Implications for patient Care: Our findings indicate that age-related degeneration in the nigrostriatal track is similar in humans and rats and that these changes can be monitored in vivo using small animal SPECT with [ 123 I]FP-CIT, which could facilitate the translational research in rat models of age related disorders of dopaminergic system

  9. Analyses of magnetic structures and nuclear-density distribution by the structure-refinement and three-dimensional visualization systems RIETAN-FP-VENUS

    International Nuclear Information System (INIS)

    Izumi, Fujio; Momma, Koichi

    2010-01-01

    We have been developing a multi-purpose pattern-fitting system RIETAN-FP and a three-dimensional visualization system VENUS, which have been extensively used for structure refinements of various metal and inorganic materials from neutron powder diffraction data. At first, their outlines and the history of their developments are shortly looked back. The second part describes procedures for analyzing collinear magnetic structures with the combination of VESTA in the VENUS system and RIETAN-FP by taking BiCoO 3 for instance. Finally, a new C++ program, Dysnomia, for the maximum entropy method is introduced with emphasis on its new features. Dysnomia excels its predecessor, PRIMA, in computation speed, memory efficiency, scalability, and reliability. In particular, addition of a normal-distribution constraint is effective in obtaining nuclear-density distribution that is physically and chemically reasonable. (author)

  10. [{sup 125}I]{beta}-CIT-FE and [{sup 125}I]{beta}-CIT-FP are superior to [{sup 125}I]{beta}-CIT for dopamine transporter visualization: Autoradiographic evaluation in the human brain

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, Ilonka; Hall, Haakan; Halldin, Christer; Swahn, Carl-Gunnar; Farde, Lars; Sedvall, Goeran

    1997-10-01

    The binding of the three dopamine transporter radioligands ([{sup 125}I]{beta}-CIT, [{sup 125}I]{beta}-CIT-FE, and [{sup 125}I]{beta}-CIT-FP) was studied using whole-hemisphere autoradiography on postmortem human brains. The autoradiograms revealed an intense and homogeneous labeling of the nucleus caudatus and putamen but also to varying extent to serotonergic and noradrenergic transporters of neocortex and thalamus. The order of specificity estimated (striatum over neocortex ratios) was {beta}-CIT-FP > {beta}-CIT-FE >> {beta}-CIT, suggesting that {beta}-CIT-FE and {beta}-CIT-FP should be preferred for in vivo studies of the dopamine transporter in the human brain.

  11. Improved dopamine transporter binding activity after bone marrow mesenchymal stem cell transplantation in a rat model of Parkinson's disease: small animal positron emission tomography study with F-18 FP-CIT

    Energy Technology Data Exchange (ETDEWEB)

    Park, Bok-Nam; Lee, Kwanjae; An, Young-Sil [School of Medicine, Ajou University, Department of Nuclear Medicine and Molecular Imaging, Woncheon-dong, Yeongtong-gu, Gyeonggi-do, Suwon (Korea, Republic of); Kim, Jang-Hee; Park, So Hyun [Ajou University School of Medicine, Department of Pathology, Suwon (Korea, Republic of)

    2015-05-01

    We evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) in a model of Parkinson's disease (PD) using serial F-18 fluoropropylcarbomethoxyiodophenylnortropane (FP-CIT) PET. Hemiparkinsonian rats were treated with intravenously injected BMSCs, and animals without stem cell therapy were used as the controls. Serial FP-CIT PET was performed after therapy. The ratio of FP-CIT uptake in the lesion side to uptake in the normal side was measured. The changes in FP-CIT uptake were also analyzed using SPM. Behavioural and histological changes were observed using the rotational test and tyrosine hydroxylase (TH)-reactive cells. FP-CIT uptake ratio was significantly different in the BMSCs treated group (n = 28) at each time point. In contrast, there was no difference in the ratio in control rats (n = 25) at any time point. SPM analysis also revealed that dopamine transporter binding activity was enhanced in the right basal ganglia area in only the BMSC therapy group. In addition, rats that received BMSC therapy also exhibited significantly improved rotational behaviour and preservation of TH-positive neurons compared to controls. The therapeutic effect of intravenously injected BMSCs in a rat model of PD was confirmed by dopamine transporter PET imaging, rotational functional studies, and histopathological evaluation. (orig.)

  12. Improved dopamine transporter binding activity after bone marrow mesenchymal stem cell transplantation in a rat model of Parkinson's disease: small animal positron emission tomography study with F-18 FP-CIT

    International Nuclear Information System (INIS)

    Park, Bok-Nam; Lee, Kwanjae; An, Young-Sil; Kim, Jang-Hee; Park, So Hyun

    2015-01-01

    We evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) in a model of Parkinson's disease (PD) using serial F-18 fluoropropylcarbomethoxyiodophenylnortropane (FP-CIT) PET. Hemiparkinsonian rats were treated with intravenously injected BMSCs, and animals without stem cell therapy were used as the controls. Serial FP-CIT PET was performed after therapy. The ratio of FP-CIT uptake in the lesion side to uptake in the normal side was measured. The changes in FP-CIT uptake were also analyzed using SPM. Behavioural and histological changes were observed using the rotational test and tyrosine hydroxylase (TH)-reactive cells. FP-CIT uptake ratio was significantly different in the BMSCs treated group (n = 28) at each time point. In contrast, there was no difference in the ratio in control rats (n = 25) at any time point. SPM analysis also revealed that dopamine transporter binding activity was enhanced in the right basal ganglia area in only the BMSC therapy group. In addition, rats that received BMSC therapy also exhibited significantly improved rotational behaviour and preservation of TH-positive neurons compared to controls. The therapeutic effect of intravenously injected BMSCs in a rat model of PD was confirmed by dopamine transporter PET imaging, rotational functional studies, and histopathological evaluation. (orig.)

  13. Fission product release and transport: assessment of sampling and analysis techniques for Falcon and Phebus-FP

    International Nuclear Information System (INIS)

    Armitage, B.H.; Beard, A.M.; Bowsher, B.R.

    1991-01-01

    Specific analytical techniques have been used during the Falcon experimental programme at Winfrith to provide both in-situ and post-test data on the thermal-hydraulic conditions and the physical and chemical forms of the resulting vapours and aerosols released from degrading UO 2 fuel. Some of the methods exhibited considerable promise in Falcon, and should be seriously considered for application in the forthcoming Phebus-FP tests. (author)

  14. Emerging migraine treatments and drug targets

    DEFF Research Database (Denmark)

    Olesen, Jes; Ashina, Messoud

    2011-01-01

    Migraine has a 1-year prevalence of 10% and high socioeconomic costs. Despite recent drug developments, there is a huge unmet need for better pharmacotherapy. In this review we discuss promising anti-migraine strategies such as calcitonin gene-related peptide (CGRP) receptor antagonists and 5......-hydroxytrypamine (5-HT)(1F) receptor agonists, which are in late-stage development. Nitric oxide antagonists are also in development. New forms of administration of sumatriptan might improve efficacy and reduce side effects. Botulinum toxin A has recently been approved for the prophylaxis of chronic migraine....... Tonabersat, a cortical spreading depression inhibitor, has shown efficacy in the prophylaxis of migraine with aura. Several new drug targets such as nitric oxide synthase, the 5-HT(1D) receptor, the prostanoid receptors EP(2) and EP(4), and the pituitary adenylate cyclase receptor PAC1 await development...

  15. "1"2"3I-FP-CIT SPECT findings and its clinical relevance in prodromal dementia with Lewy bodies

    International Nuclear Information System (INIS)

    Kasanuki, Koji; Iseki, Eizo; Ota, Kazumi; Kondo, Daizo; Sato, Kiyoshi; Ichimiya, Yosuke; Arai, Heii

    2017-01-01

    Evidence for the prodromal stage of dementia with Lewy bodies (DLB) is very limited. To address this issue, we investigate the "1"2"3I-FP-CIT SPECT measure of dopamine transporter binding finding and its clinical relevance. We enrolled subjects into a prodromal DLB group (PRD-DLB) (n = 20) and clinical DLB group (CLIN-DLB) (n = 18) and compared these groups with an Alzheimer's disease control group (AD) (n = 10). PRD-DLB was defined as patients having the non-motor symptoms associated with Lewy body disease (LBD) [i.e. REM sleep behavior disorder (RBD), olfactory dysfunction, autonomic dysfunction, and depression] and showing characteristic diffuse occipital hypometabolism in "1"8F-FDG PET. CLIN-DLB was defined as patients fulfilling the established criteria of probable DLB. Striatal specific binding ratio (SBR) of "1"2"3I-FP-CIT SPECT was used for objective group comparisons. The correlations between SBR and cognitive function (MMSE), motor symptoms (UPDRS3), and duration of LBD-associated non-motor symptoms were compared between the two DLB groups. Mean SBR scores of both PRD-DLB and CLIN-DLB were significantly lower than those of AD. No correlation was found between SBR and MMSE scores. Both in the CLIN-DLB and total DLB groups, SBR scores were negatively correlated with UPDRS3 scores, whereas no correlation was found in PRD-DLB. Among the LBD-related non-motor symptoms, duration of olfactory dysfunction, and RBD demonstrated negative correlation with SBR scores in PRD-DLB. "1"2"3I-FP-CIT SPECT may play a role for detecting DLB among the subjects in prodromal stage. During this stage, long-term olfactory dysfunction and/or RBD may indicate more severe degeneration of the nigro-striatal dopaminergic pathway. (orig.)

  16. Comparison of the performance of {sup 18}F-FP-CIT brain PET/MR and simultaneous PET/CT: A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Sang Don; Chun, Kyung Ah [Dept. of Nuclear Medicine, Yeungnam University Hospital, Daegu (Korea, Republic of)

    2016-09-15

    {sup 18}F-FP-CIT [{sup 1'}8F-fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane] has been well established and used for the differential diagnosis of atypical parkinsonian disorders. Recently, combined positron emission tomography (PET)/magnetic resonance (MR) was proposed as a viable alternative to PET/computed tomography (CT). The aim of this study was to compare the performances of conventional {sup 18}F-FP-CIT brain PET/CT and simultaneous PET/MR by visual inspection and quantitative analysis. Fifteen consecutive patients clinically suspected of having Parkinson's disease were recruited for the study.{sup 18}F-FP-CIT PET was performed during PET/CT and PET/MR. PET/CT image acquisition was started 90 min after intravenous injection of {sup 18}F-FP-CIT and then PET/MR images were acquired. Dopamine transporter (DAT) density in bilateral striatal subregions was assessed visually. Quantitative analyses were performed on bilateral striatal volumes of interest (VOIs) using average standardized uptake values (SUVmeans). Intraclass correlation coefficients (ICCs) and their 95 % confidence intervals (CIs) were assessed to compare PET/CT and PET/MR data. Bland-Altman plots were drawn to perform method-comparisons. All subjects showed a preferential decrease in DAT binding in the posterior putamen (PP), with relative sparing of the ventral putamen (VP). Bilateral striatal subregional binding ratio (BR) determined PET/CT and PET/MR demonstrated close interequipment correspondence (BRright caudate - ICC, 0.944; 95 % CI, 0.835-0.981, BRleft caudate - ICC, 0.917; 95 % CI, 0.753-0.972, BRright putamen - ICC, 0.976; 95 % CI, 0.929-0.992 and BRleft putamen - ICC, 0.970; 95 % CI, 0.911-0.990, respectively), and Bland-Altman plots showed interequipment agreement between the two modalities. It is known that MR provides more information about anatomical changes associated with brain diseases and to enable the anatomical allocations of

  17. A comparison of core degradation phenomena in the CORA, QUENCH, Phébus SFD and Phébus FP experiments

    Energy Technology Data Exchange (ETDEWEB)

    Haste, T., E-mail: tim.haste@irsn.fr [Institut de Radioprotection et de Sûreté Nucléaire, IRSN, BP 3, F-13115 St. Paul-lez-Durance Cedex (France); Steinbrück, M., E-mail: martin.steinbrueck@kit.edu [Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen (Germany); Barrachin, M., E-mail: marc.barrachin@irsn.fr [Institut de Radioprotection et de Sûreté Nucléaire, IRSN, BP 3, F-13115 St. Paul-lez-Durance Cedex (France); Luze, O. de, E-mail: olivier.de-luze@irsn.fr [Institut de Radioprotection et de Sûreté Nucléaire, IRSN, BP 3, F-13115 St. Paul-lez-Durance Cedex (France); Grosse, M., E-mail: mirco.grosse@kit.edu [Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen (Germany); Stuckert, J., E-mail: juri.stuckert@kit.edu [Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen (Germany)

    2015-03-15

    Highlights: • The results of the experiments CORA, QUENCH and Phébus SFD/FP are summarised. • All phenomena expected up to melt movement to the lower head are shown consistently. • Separate-effect tests performed at KIT and IRSN aid improve their modelling. • Data from the integral tests help independent validation of new and improved models. • The improved codes will help reduce uncertainties in safety-critical areas for core degradation. - Abstract: Over the past 20 years, integral fuel bundle experiments performed at IRSN Cadarache, France (Phébus-SFD and Phébus FP – fission heated) and at Karlsruhe Institute of Technology, Germany (CORA and QUENCH – electrically heated), accompanied by separate-effect tests, have provided a wealth of detailed information on core degradation phenomena that occur under severe accident conditions, relevant to such safety issues as in-vessel retention of the core, recovery of the core by water reflood, hydrogen generation and fission product release. These data form an important basis for development and validation of severe accident analysis codes such as ASTEC (IRSN/GRS, EC) and MELCOR (USNRC/SNL, USA) that are used to assess the safety of current and future reactor designs, so helping to reduce the uncertainty associated with such code predictions. Following the recent end of the Phébus FP project, it is appropriate now to compare the core degradation phenomena observed in these four major experimental series, indicating the main conclusions that have been drawn. This covers subjects such as early phase degradation up to loss of rod-like geometry (all the series), late phase degradation and the link between fission product release and core degradation (Phébus FP), oxidation phenomena (all the series), reflood behaviour (CORA and QUENCH), as well as particular topics such as the effects of control rod material and fuel burn-up on core degradation. It also outlines the separate-effects experiments performed to

  18. Effects of the dual TP receptor antagonist and thromboxane synthase inhibitor EV-077 on human endothelial and vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Petri, Marcelo H.; Tellier, Céline; Michiels, Carine; Ellertsen, Ingvill; Dogné, Jean-Michel; Bäck, Magnus

    2013-01-01

    Highlights: •EV-077 reduced TNF-α induced inflammation in endothelial cells. •The thromboxane mimetic U69915 enhanced vascular smooth muscle cell proliferation. •EV-077 inhibited smooth muscle cell proliferation. -- Abstract: The prothrombotic mediator thromboxane A 2 is derived from arachidonic acid metabolism through the cyclooxygenase and thromboxane synthase pathways, and transduces its effect through the thromboxane prostanoid (TP) receptor. The aim of this study was to determine the effect of the TP receptor antagonist and thromboxane synthase inhibitor EV-077 on inflammatory markers in human umbilical vein endothelial cells and on human coronary artery smooth muscle cell proliferation. To this end, mRNA levels of different proinflammatory mediators were studied by real time quantitative PCR, supernatants were analyzed by enzyme immune assay, and cell proliferation was assessed using WST-1. EV-077 significantly decreased mRNA levels of ICAM-1 and PTX3 after TNFα incubation, whereas concentrations of 6-keto PGF1α in supernatants of endothelial cells incubated with TNFα were significantly increased after EV-077 treatment. Although U46619 did not alter coronary artery smooth muscle cell proliferation, this thromboxane mimetic enhanced the proliferation induced by serum, insulin and growth factors, which was significantly inhibited by EV-077. In conclusion, EV-077 inhibited TNFα-induced endothelial inflammation and reduced the enhancement of smooth muscle cell proliferation induced by a thromboxane mimetic, supporting that the thromboxane pathway may be associated with early atherosclerosis in terms of endothelial dysfunction and vascular hypertrophy

  19. Effects of the dual TP receptor antagonist and thromboxane synthase inhibitor EV-077 on human endothelial and vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Petri, Marcelo H. [Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm (Sweden); Tellier, Céline; Michiels, Carine [NARILIS, URBC, University of Namur, Namur (Belgium); Ellertsen, Ingvill [Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm (Sweden); Dogné, Jean-Michel [Department of Pharmacy, Namur Thrombosis and Hemostasis Center, University of Namur, Namur (Belgium); Bäck, Magnus, E-mail: Magnus.Back@ki.se [Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm (Sweden)

    2013-11-15

    Highlights: •EV-077 reduced TNF-α induced inflammation in endothelial cells. •The thromboxane mimetic U69915 enhanced vascular smooth muscle cell proliferation. •EV-077 inhibited smooth muscle cell proliferation. -- Abstract: The prothrombotic mediator thromboxane A{sub 2} is derived from arachidonic acid metabolism through the cyclooxygenase and thromboxane synthase pathways, and transduces its effect through the thromboxane prostanoid (TP) receptor. The aim of this study was to determine the effect of the TP receptor antagonist and thromboxane synthase inhibitor EV-077 on inflammatory markers in human umbilical vein endothelial cells and on human coronary artery smooth muscle cell proliferation. To this end, mRNA levels of different proinflammatory mediators were studied by real time quantitative PCR, supernatants were analyzed by enzyme immune assay, and cell proliferation was assessed using WST-1. EV-077 significantly decreased mRNA levels of ICAM-1 and PTX3 after TNFα incubation, whereas concentrations of 6-keto PGF1α in supernatants of endothelial cells incubated with TNFα were significantly increased after EV-077 treatment. Although U46619 did not alter coronary artery smooth muscle cell proliferation, this thromboxane mimetic enhanced the proliferation induced by serum, insulin and growth factors, which was significantly inhibited by EV-077. In conclusion, EV-077 inhibited TNFα-induced endothelial inflammation and reduced the enhancement of smooth muscle cell proliferation induced by a thromboxane mimetic, supporting that the thromboxane pathway may be associated with early atherosclerosis in terms of endothelial dysfunction and vascular hypertrophy.

  20. Computer program system for evaluation of FP nuclear data for JENDL. Smooth part

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, Tsuneo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Watanabe, Takashi; Iijima, Shungo

    1997-12-01

    This report describes computer programs used to evaluate nuclear data of fission product (FP) nuclides stored in an evaluated nuclear data library JENDL, especially in the smooth part above the resonance region. Many programs were used for determination of nuclear model parameters, calculation of nuclear data, handling of experimental and/or calculated data, and so on. Among them, reported here are programs for determination of level density parameters (ENSDFRET, LVLPLOT, LEVDES), for making sets of JCL and input data for the theoretical calculation program CASTHY (JOBSETTER, INDES/CASTHY), and for conversion of format of CASTHY output files to the ENDF format (CTOB2). (author). 51 refs.

  1. Difluoro-lambda(5)-phosphinonitrile F(2)P[triple bond]N: matrix isolation and photoisomerization into FP=NF.

    Science.gov (United States)

    Zeng, Xiaoqing; Beckers, Helmut; Willner, Helge

    2009-01-01

    Splendid isolation: Monomeric phosphazene F(2)PN ((1)A(1)) was prepared for the first time through irradiation of F(2)PN(3) in an argon matrix with an ArF excimer laser (lambda=193 nm). Upon subsequent irradiation with a high-pressure mercury arc lamp (lambda=255 nm), F(2)PN undergoes a 1,2-fluorine shift to give iminophosphane cis-FP=NF.

  2. Projects and potentialities for Scientific and Technological Cooperation between Mexico and Thailand under the European Union's Seventh Framework Program (FP7: 2007-2013

    Directory of Open Access Journals (Sweden)

    Jürgen Haberleithner

    2012-09-01

    Full Text Available The European Union and Mexico have been cooperating in the field of R&D since the partnership treaty between the Eu and Mexico took effect in 2000. With the Lisbon Strategy put into operation that same year, Europe acknowledged the central role which will be played by knowledge in the economy and society of the future. Accordingly, innovation was emphasized in order to advance mutual efforts to establish innovative research and development projects with Third Countries such as Mexico and Thailand through diverse multilateral framework programs such as the Seventh Framework Program (Fp7. A brief evaluation of the existing projects in Fp7 reveal disposition for intraregional cooperation in spite of the disparities regarding the quantity and extension of projects. Moreover, studied participants share a similar lack of know-how for coordinating projects which is at times crucial for benefiting completely from the program. Potential exists for establishing the necessary links and coordinating points amongst Mexico and Thailand under the given cooperation regional and bilateral mechanisms and the extensive research areas that the program covers. It is these specific potentialities enabled by the Fp7 in both regions that intend to be further researched for their development into multiple and successful projects.

  3. Vitamin D receptor is present on the neuronal plasma membrane and is co-localized with amyloid precursor protein, ADAM10 or Nicastrin.

    Science.gov (United States)

    Dursun, Erdinç; Gezen-Ak, Duygu

    2017-01-01

    Our recent study indicated that vitamin D and its receptors are important parts of the amyloid processing pathway in neurons. Yet the role of vitamin D receptor (VDR) in amyloid pathogenesis is complex and all regulations over the production of amyloid beta cannot be explained solely with the transcriptional regulatory properties of VDR. Given that we hypothesized that VDR might exist on the neuronal plasma membrane in close proximity with amyloid precursor protein (APP) and secretase complexes. The present study primarily focused on the localization of VDR in neurons and its interaction with amyloid pathology-related proteins. The localization of VDR on neuronal membranes and its co-localization with target proteins were investigated with cell surface staining followed by immunofluorescence labelling. The FpClass was used for protein-protein interaction prediction. Our results demonstrated the localization of VDR on the neuronal plasma membrane and the co-localization of VDR and APP or ADAM10 or Nicastrin and limited co-localization of VDR and PS1. E-cadherin interaction with APP or the γ-secretase complex may involve NOTCH1, NUMB, or FHL2, according to FpClass. This suggested complex might also include VDR, which greatly contributes to Ca+2 hemostasis with its ligand vitamin D. Consequently, we suggested that VDR might be a member of this complex also with its own non-genomic action and that it can regulate the APP processing pathway in this way in neurons.

  4. Synthesis of C3, C5, and C7 pregnane derivatives and their effect on NMDA receptor responses in cultured rat hippocampal neurons

    Czech Academy of Sciences Publication Activity Database

    Šťastná, Eva; Chodounská, Hana; Pouzar, Vladimír; Kapras, Vojtěch; Borovská, Jiřina; Cais, Ondřej; Vyklický ml., Ladislav

    2009-01-01

    Roč. 74, č. 2 (2009), s. 256-263 ISSN 0039-128X R&D Projects: GA ČR(CZ) GA309/07/0271; GA ČR(CZ) GA203/08/1498 Grant - others:GA MŠk(CZ) LC554; FP6 Photolysis(XE) LSHM-CT-2007-037765 Program:LC Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50110509 Keywords : pregnane derivatives * NMDA receptor * structure-activity relationship * patch-clamp recording Subject RIV: CC - Organic Chemistry Impact factor: 2.905, year: 2009

  5. Fructose intake exacerbates the contractile response elicited by norepinephrine in mesenteric vascular bed of rats via increased endothelial prostanoids.

    Science.gov (United States)

    Sousa, Glauciene J; Oliveira, Phablo Wendell C; Nogueira, Breno V; Melo, Antônio F; Faria, Thaís de Oliveira; Meira, Eduardo Frizera; Mill, José G; Bissoli, Nazaré S; Baldo, Marcelo P

    2017-10-01

    Chronic fructose intake induces major cardiovascular and metabolic disturbances and is associated with the development of hypertension due to changes in vascular function. We hypothesized that high fructose intake for 6 weeks would cause metabolic syndrome and lead to initial vascular dysfunction. Male Wistar rats were assigned to receive fructose (FRU, 10%) or drinking water (CON) for 6 weeks. Systolic blood pressure was evaluated by tail plethysmography. Fasting glucose, insulin and glucose tolerance were measured at the end of the follow-up. Mesenteric vascular bed reactivity was tested before and after pharmacological blockade. Western blot analysis was performed for iNOS, eNOS, Nox2 and COX-2. DHE staining was used for vascular superoxide anion detection. Vessel structure was evaluated by optical and electronic microscopy. Fructose intake did not alter blood pressure, but did increase visceral fat deposition and fasting glucose as well as impair insulin and glucose tolerance. Fructose increased NE-induced vasoconstriction compared with CON, and this difference was abrogated by indomethacin perfusion as well as endothelium removal. ACh-induced relaxation was preserved, and the NO modulation tested after L-NAME perfusion was similar between groups. SNP-induced relaxation was not altered. Inducible NOS was increased; however, there were no changes in eNOS, Nox2 or COX-2 protein expression. Basal or stimulated superoxide anion production was not changed by fructose intake. In conclusion, high fructose intake increased NE-induced vasoconstriction through the endothelial prostanoids even in the presence of a preserved endothelium-mediated relaxation. No major changes in vessel structure were detected. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. COST action FP801- established and emerging Phytophthora: incresasing threats to woodland and forest ecosystems in Europe

    OpenAIRE

    Woodward, S.; Vannini, A.; Werres, S.; Osswald, W.; Bonants, P.J.M.; Jung, T.

    2011-01-01

    With the rapidly growing international trade in plants and ongoing impacts of climate change, impacts of plant pathogens in the genus Phytophthora are increasing, threatening the biodiversity and sustainability of European forest ecosystems. Through the European Cooperation in Science and Technology (COST) framework Action FP0801, scientists and disease-control experts are working on phytophthora in forest ecosystems with the overall aim of increasing understanding of the biology and ecology ...

  7. New semiquantitative assessment of 123I-FP-CIT by an anatomical standardization method

    International Nuclear Information System (INIS)

    Takada, Seiko; Yoshimura, Mana; Shindo, Hiroaki; Saito, Kazuhiro; Koizumi, Kiyoshi; Utsumi, Hiroya; Abe, Kimihiko

    2006-01-01

    We evaluated a new semiquantitative procedure to more easily and objectively estimate the striatal uptake of 123 I-FP-CIT in patients with Parkinsonian syndrome (PS) and essential tremor (ET), using an anatomical standardization method, the Neurostat. Eleven patients with PS and 8 with ET were examined by clinical assessment and 123 I-FP-CIT SPECT imaging. The modified Hoehn and Yahr Staging Scale and Unified Parkinson's Disease Rating Scale (UPDRS) were used to assess the stage and severity of the disease. The co-registered MR and SPECT images were created with fusion software included in Neurostat. On the cross section, which shows the largest area of striate, irregular shaped regions of interest corresponding to the striate and occipital cortex were drawn. Then the ratio of specific striatal uptake to non-specific occipital cortex, V3''(F), was calculated. Another calculation was done by VOIClassic, which is a software included in Neurostat to estimate the counts per voxel of anatomically defined regions such as caudate nucleus, putamen, occipital cortex, and total cortex. Using these count data, the ratio of specific striatal uptake to non-specific occipital cortex, V3''(OC), and total cortex, V3''(TC), was calculated. A fair linear correlation was observed between V3''(OC) and V3''(F) (y=1.53x+1.40; r=0.756; p s =-0.816). However, V3''(OC) and V3''(TC) correlated less with UPDRS (r s =-0.667 and -0.645, respectively). Semiquantitative parameters, V3''(OC) and V3''(TC), calculated by VOIClassic including the Neurostat system are useful and easily calculable parameters as well as V3''(F) for the differential diagnosis of PS from ET. (author)

  8. Loss of Substantia Nigra Hyperintensity at 3.0-T MR Imaging in Idiopathic REM Sleep Behavior Disorder: Comparison with 123I-FP-CIT SPECT.

    Science.gov (United States)

    Bae, Yun Jung; Kim, Jong-Min; Kim, Kyeong Joon; Kim, Eunhee; Park, Hyun Soo; Kang, Seo Young; Yoon, In-Young; Lee, Jee-Young; Jeon, Beomseok; Kim, Sang Eun

    2018-04-01

    Purpose To examine whether the loss of nigral hyperintensity (NH) on 3.0-T susceptibility-weighted (SW) magnetic resonance (MR) images can help identify high synucleinopathy risk in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). Materials and Methods Between March 2014 and April 2015, 18 consecutively recruited patients with iRBD were evaluated with 3.0-T SW imaging and iodine 123-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane ( 123 I-FP-CIT) single photon emission computed tomography and compared with 18 healthy subjects and 18 patients with Parkinson disease (PD). Two readers blinded to clinical diagnosis independently assessed the images. 123 I-FP-CIT uptake ratios were compared by using the Kruskal-Wallis test, and intra- and interobserver agreements were assessed with the Cohen κ. The synucleinopathy conversion according to NH status was evaluated in patients with iRBD after follow-up. Results NH was intact in seven patients with iRBD and lost in 11. The 123 I-FP-CIT uptake ratios were comparable between those with intact NH (mean, 3.22 ± 0.47) and healthy subjects (mean, 3.37 ± 0.47) (P = .495). The 123 I-FP-CIT uptake ratios in the 11 patients with iRBD and NH loss (mean, 2.48 ± 0.44) were significantly lower than those in healthy subjects (mean, 3.37 ± 0.47; P 0.9). Five patients with iRBD and NH loss developed symptoms of parkinsonism or dementia 18 months after neuroimaging. Conclusion NH loss at 3.0-T SW imaging may be a promising marker for short-term synucleinopathy risk in iRBD. © RSNA, 2017 Online supplemental material is available for this article.

  9. Phebus FP: organisation of the project and international collaboration

    International Nuclear Information System (INIS)

    Tattegrain, A.; Hardt, P. von der

    1992-01-01

    PHEBUS Fission Product (FP) Research Programme developed from the initial French design study into a European project, and further into an international programme by agreements with overseas partners during the past two years. The programme is supervised by a Steering Committee which reviews the technical-scientific options and the results. The executive body under the Committee, the Project Group, includes a Commissariat a l'Energie Atomique (CEA) and Commission of the European Communities (CEC) manager as well as three (CEA) project leaders for design and manufacture, experiment operation, and interpretation of test results. The Steering Committee can request expertise from the two working groups the Analytical Group (SAWG) (elaborating test objectives, carrying out reactor calculations and test precalculations) and the Technical Group (TG) (assessing the designs proposed and the results obtained by the Project Group). A third group looks into financial aspects of the CEA-CEC contract only. The two working groups, SAWG and TG, play an important role in the exchange of information and of expertise between all partners. The paper reviews the internal Project organisation and the collaboration network, inside the European Community and through CEA overseas. (author)

  10. The cost effectiveness of 123I-FP-CIT SPECT imaging in patients with an uncertain clinical diagnosis of parkinsonism

    International Nuclear Information System (INIS)

    Laere, Koen van; Everaert, Ludwig; Annemans, Lieven; Gonce, Michel; Vandenberghe, Wim; Vander Borght, Thierry

    2008-01-01

    123 I-N-ω-fluoropropyl-2-β-carboxymethoxy-3β-(4-iodophenyl )nortropane ( 123 I-FP-CIT) Single-photon emission computed tomography (SPECT) has been suggested to be a useful diagnostic adjunct in patients with clinically uncertain parkinsonism. We developed a pharmaco-economic (PE) model, evaluating the cost effectiveness of adding 123 I-FP-CIT SPECT to the diagnostic workup. As the model was developed before application of the diagnostic technique in real practice, a predictive validity assessment was performed based on data from a large nationwide patient registry in these patients. A PE model, using a Markov state transition model, was created, based on literature-derived and clinical expert panel data. Effects were expressed as adequately treated years (ATY). Key input data were compared to the real-life patterns in a nationwide multi-centre clinical setting, based on a complete national registry of 1,701 consecutive patients. The change in initial diagnosis and alteration of management of the patient after SPECT were registered. In the PE model, it was calculated that management would change in 48.5% of patients by SPECT and that, over a 5-year period, 1.2 ATYs could be gained at a yearly additional cost of EUR72. From the studied 1,701 patients, nigrostriatal degeneration was observed in 59.8%, the initial diagnosis was changed in 51.5%, management was altered in 49%, and cost effectiveness was increased to EUR358 per ATY. Good correspondence between assumed and observed changes in patient management was found, indicating that 123 I-FP-CIT SPECT is influential in diagnosis and management of patients with uncertain clinical diagnosis of parkinsonism. This can be achieved at a marginal added cost to the health insurance and leads to a significant gain in ATY. (orig.)

  11. Development of methodology for alternative testing strategies for the assessment of the toxicological profile of nanoparticles used in medical diagnostics. NanoTEST - EC FP7 project

    International Nuclear Information System (INIS)

    Dusinska, Maria; Fjellsbo, Lise Maria; Heimstad, Eldbjorg; Harju, Mikael; Bartonova, Alena; Tran, Lang; Juillerat-Jeanneret, Lucienne; Halamoda, Blanka; Marano, Francelyne; Boland, Sonja; Saunders, Margaret; Cartwright, Laura; Carreira, Sara; Thawley, Susan; Whelan, Maurice; Klein, Christoph; Housiadas, Christos; Volkovova, Katarina; Tulinska, Jana; Beno, Milan

    2009-01-01

    Nanoparticles (NPs) have unique, potentially beneficial properties, but their possible impact on human health is still not known. The area of nanomedicine brings humans into direct contact with NPs and it is essential for both public confidence and the nanotech companies that appropriate risk assessments are undertaken in relation to health and safety. There is a pressing need to understand how engineered NPs can interact with the human body following exposure. The FP7 project NanoTEST (www.nanotest-fp7.eu) addresses these requirements in relation to the toxicological profile of NPs used in medical diagnostics.

  12. FP-LAPW study of the elastic properties of Al2X (X=Sc,Y,La,Lu)

    International Nuclear Information System (INIS)

    Rajagopalan, M.; Praveen Kumar, S.; Anuthama, R.

    2010-01-01

    From the first principles total energy calculations based on full-potential linear augmented plane wave method (FP-LAPW), the elastic properties of Al 2 X (X=Sc,Y,La,Lu) are reported here. Theoretical values of Young's modulus, shear modulus, Poisson's ratio and Debye temperature are estimated from the computed elastic constants. From the analysis of the ratio of shear to bulk modulus, it is found that these intermetallic compounds are brittle in nature. The calculated results are compared with other reported values.

  13. Social Franchising: A Blockbuster to Address Unmet Need for Family Planning and to Advance Toward the FP2020 Goal.

    Science.gov (United States)

    2015-06-17

    Social franchising has scaled-up provision of voluntary family planning, especially long-acting reversible contraceptives, across Africa and Asia at a rapid and remarkable pace. The approach should be pursued vigorously, especially in countries with a significant private-sector presence, to advance the FP2020 goal of providing access to modern contraception to 120 million additional clients by 2020.

  14. Evaluation of the Barr & Stroud FP15 and Criterion 400 laser dendrometers for measuring upper stem diameters and heights

    Science.gov (United States)

    Michael S. Williams; Kenneth L. Cormier; Ronald G. Briggs; Donald L. Martinez

    1999-01-01

    Calibrated Barr & Stroud FP15 and Criterion 400 laser dendrometers were tested for reliability in measuring upper stem diameters and heights under typical field conditions. Data were collected in the Black Hills National Forest, which covers parts of South Dakota and Wyoming in the United States. Mixed effects models were employed to account for differences between...

  15. ENVIRONMENTAL TECHNOLOGY VERIFICATION, TEST REPORT OF CONTROL OF BIOAEROSOLS IN HVAC SYSTEMS, FILTRATION GROUP, AEROSTAR FP-98 MINIPLEAT V-BLANK FILTER

    Science.gov (United States)

    The Environmental Technology Verification report discusses the technology and performance of the AeroStar FP-98 Minipleat V-Bank Filter air filter for dust and bioaerosol filtration manufactured by Filtration Group. The pressure drop across the filter was 137 Pa clean and 348 Pa ...

  16. EU-funded research in nuclear fission with emphasis on operational safety of existing installations: main achievements of FP-4 (1994-1998), some preliminary results of FP-5 (1998-2002) and prospects for beyond 2002

    International Nuclear Information System (INIS)

    Van Goethem, G.; Bermejo, J.M.; Zurita, A.; Lemaitre, P.

    2001-01-01

    In this paper an overview is given of the most important aspects of the research activities organised by the European Union (EU) in the area ''Operational Safety of Existing installation'' of the Key Action NUCLEAR FISSION of the 5. EURATOM framework programme (FP-5) 1998-2002, with emphasis on plant life extension and management (PLEM), severe accident management (SAM) and evolutionary safety concepts (EVOL). The strategic goal of this specific programme 1998-2002 is to help exploit the full potential of nuclear energy in a sustainable manner, by making current technologies even safer and more economical and by exploring promising new concepts. (author)

  17. Validation of Simple Quantification Methods for (18)F-FP-CIT PET Using Automatic Delineation of Volumes of Interest Based on Statistical Probabilistic Anatomical Mapping and Isocontour Margin Setting.

    Science.gov (United States)

    Kim, Yong-Il; Im, Hyung-Jun; Paeng, Jin Chul; Lee, Jae Sung; Eo, Jae Seon; Kim, Dong Hyun; Kim, Euishin E; Kang, Keon Wook; Chung, June-Key; Lee, Dong Soo

    2012-12-01

    (18)F-FP-CIT positron emission tomography (PET) is an effective imaging for dopamine transporters. In usual clinical practice, (18)F-FP-CIT PET is analyzed visually or quantified using manual delineation of a volume of interest (VOI) for the striatum. In this study, we suggested and validated two simple quantitative methods based on automatic VOI delineation using statistical probabilistic anatomical mapping (SPAM) and isocontour margin setting. Seventy-five (18)F-FP-CIT PET images acquired in routine clinical practice were used for this study. A study-specific image template was made and the subject images were normalized to the template. Afterwards, uptakes in the striatal regions and cerebellum were quantified using probabilistic VOI based on SPAM. A quantitative parameter, QSPAM, was calculated to simulate binding potential. Additionally, the functional volume of each striatal region and its uptake were measured in automatically delineated VOI using isocontour margin setting. Uptake-volume product (QUVP) was calculated for each striatal region. QSPAM and QUVP were compared with visual grading and the influence of cerebral atrophy on the measurements was tested. Image analyses were successful in all the cases. Both the QSPAM and QUVP were significantly different according to visual grading (P Simple quantitative measurements of QSPAM and QUVP showed acceptable agreement with visual grading. Although QSPAM in some group may be influenced by cerebral atrophy, these simple methods are expected to be effective in the quantitative analysis of (18)F-FP-CIT PET in usual clinical practice.

  18. Validation of simple quantification methods for 18F FP CIT PET Using Automatic Delineation of volumes of interest based on statistical probabilistic anatomical mapping and isocontour margin setting

    International Nuclear Information System (INIS)

    Kim, Yong Il; Im, Hyung Jun; Paeng, Jin Chul; Lee, Jae Sung; Eo, Jae Seon; Kim, Dong Hyun; Kim, Euishin E.; Kang, Keon Wook; Chung, June Key; Lee Dong Soo

    2012-01-01

    18 F FP CIT positron emission tomography (PET) is an effective imaging for dopamine transporters. In usual clinical practice, 18 F FP CIT PET is analyzed visually or quantified using manual delineation of a volume of interest (VOI) fir the stratum. in this study, we suggested and validated two simple quantitative methods based on automatic VOI delineation using statistical probabilistic anatomical mapping (SPAM) and isocontour margin setting. Seventy five 18 F FP CIT images acquired in routine clinical practice were used for this study. A study-specific image template was made and the subject images were normalized to the template. afterwards, uptakes in the striatal regions and cerebellum were quantified using probabilistic VOI based on SPAM. A quantitative parameter, Q SPAM, was calculated to simulate binding potential. additionally, the functional volume of each striatal region and its uptake were measured in automatically delineated VOI using isocontour margin setting. Uptake volume product(Q UVP) was calculated for each striatal region. Q SPAMa nd Q UVPw as calculated for each visual grading and the influence of cerebral atrophy on the measurements was tested. Image analyses were successful in all the cases. Both the Q SPAMa nd Q UVPw ere significantly different according to visual grading (0.001). The agreements of Q UVPa nd Q SPAMw ith visual grading were slight to fair for the caudate nucleus (K= 0.421 and 0.291, respectively) and good to prefect to the putamen (K=0.663 and 0.607, respectively). Also, Q SPAMa nd Q UVPh ad a significant correlation with each other (0.001). Cerebral atrophy made a significant difference in Q SPAMa nd Q UVPo f the caudate nuclei regions with decreased 18 F FP CIT uptake. Simple quantitative measurements of Q SPAMa nd Q UVPs howed acceptable agreement with visual grad-ing. although Q SPAMi n some group may be influenced by cerebral atrophy, these simple methods are expected to be effective in the quantitative analysis of F FP

  19. Determination of tea fluorine concentration with 19F(p, αγ)16O prompt nuclear reaction analysis

    International Nuclear Information System (INIS)

    Liang Daihua; Shen Guantao; Li Deyi; Wu Junheng

    1987-01-01

    Experiments of 19 F(p, αγ) 16 O prompt nuclear reaction analyses of tea F contents were performed on a Cockroft-Walton accelerator. The principle and apparatus are described. More than 150 varieties tea samples were examined. Results show that for the same variety of tea samples, the higher the grade of the tea, the higher the F concentration it contains, and for different varieties, the better the tea, the lower the F concentration of the tea

  20. Δ9-THC-Caused Synaptic and Memory Impairments Are Mediated through COX-2 Signaling

    OpenAIRE

    Chen, Rongqing; Zhang, Jian; Fan, Ni; Teng, Zhao-qian; Wu, Yan; Yang, Hongwei; Tang, Ya-ping; Sun, Hao; Song, Yunping; Chen, Chu

    2013-01-01

    Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here we show that synaptic and cognitive impairments following repeated exposure to Δ9-tetrahydrocannabinol (Δ9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids, in the brain. COX-2 induction by Δ9-THC is mediated via CB1 receptor-coupled G-protein βγ subunits. Pharmaco...

  1. Development and validation of the aerosol transport module gamma-FP for evaluating radioactive fission product source terms in a VHTR

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Churl; Lim, Hong Sik [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-12-15

    Predicting radioactive fission product (FP) behaviors in the reactor coolant system and the containment of a nuclear power plant (NPP) is one of the major concerns in the field of reactor safety, since the amount of radioactive FP released into the environment during the postulated accident sequences is one of the major regulatory issues. Radioactive FPs circulating in the primary coolant loop and released into the containment are basically in the form of gas or aerosol. In this study, a multi-component and multi-sectional analysis module for aerosol fission products has been developed based on the MAEROS model, and the aerosol transport model has been developed and verified against an analytic solution. The deposition of aerosol FPs to the surrounding structural surfaces is modeled with recent research achievements. The developed aerosol analysis model has been successfully validated against the STORM SR-11 experimental data, which is International Standard Problem No. 40. Future studies include the development of the resuspension, growth, and chemical reaction models of aerosol fission products.

  2. FP-LAPW Calculations of the EFG at Cd Impurities in Rutile SnO2

    International Nuclear Information System (INIS)

    Errico, L. A.; Fabricius, G.; Renteria, M.

    2001-01-01

    We report an ab initio study of the electric-field gradient (EFG) at Cd impurities located at the cation site in the semiconductor SnO 2 (rutile phase). The study was performed with the WIEN97 implementation of the FP-LAPW method. In order to simulate the diluted Cd-impurity in the SnO 2 host and to calculate the electronic structure of the system we used a 72-atoms super-cell, studying the relaxation introduced by the impurity in the lattice. The free-relaxation process performed shows that the relaxations of the oxygen nearest-neighbors of the impurity are not isotropic. Our prediction for the EFG tensor are compared with experimental results and point-charge model predictions

  3. Intranasal dopamine reduces in vivo [123I]FP-CIT binding to striatal dopamine transporter: correlation with behavioral changes and evidence for Pavlovian conditioned dopamine response

    Directory of Open Access Journals (Sweden)

    Maria A de Souza Silva

    2016-04-01

    Full Text Available Purpose: Dopamine (DA, which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA, nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [123I]FP-CIT to the DAT should be decreased due to competition at the receptor.Methods: Rats were administered intranasal application of 3 mg/kg IN-DA and vehicle (VEH, with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming were assessed for 30 min in an open field prior to administration of [123I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT two hours following administration of the radioligand. Results: 1 After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered dopamine had central action and increased DA levels comparable to that found previously with L-DOPA administration. 2 DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant

  4. Intranasal Dopamine Reduces In Vivo [(123)I]FP-CIT Binding to Striatal Dopamine Transporter: Correlation with Behavioral Changes and Evidence for Pavlovian Conditioned Dopamine Response.

    Science.gov (United States)

    de Souza Silva, Maria A; Mattern, Claudia; Decheva, Cvetana; Huston, Joseph P; Sadile, Adolfo G; Beu, Markus; Müller, H-W; Nikolaus, Susanne

    2016-01-01

    Dopamine (DA), which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA), nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT) binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [(123)I]FP-CIT to the DAT should be decreased due to competition at the receptor. Rats were administered 3 mg/kg IN-DA and vehicle (VEH), with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming) were assessed for 30 min in an open field prior to administration of [(123)I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT 2 h following administration of the radioligand. (1) After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered DA had central action and increased DA levels comparable to that found previously with L-DOPA administration; and (2) DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased) the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant drugs. (a) demonstrate a direct central action of intranasally

  5. Cytotoxic and pro-oxidative effects of Imperata cylindrica aerial part ethyl acetate extract in colorectal cancer in vitro.

    Science.gov (United States)

    Kwok, Amy Ho Yan; Wang, Yan; Ho, Wing Shing

    2016-05-15

    Colorectal cancer (CRC) is the third most common cancer. Its global incidence and mortality have been on the rise. Recent strategy of therapies has involved the use of non-steroid anti-inflammatory drugs and cyclooxygenase-selective inhibitors. Aerial parts of Imperata cylindrical L. Raeusch (IMP) have been used as an anti-inflammatory agent in traditional Chinese medicine. Asarachidonate acid cascadeis often involved in inflammation-related malignancy and IMP is an anti-inflammatory agent, hence it is hypothesized that IMP aerial part ethyl acetate extract exerts cytotoxic effects on colorectal cancer cells in vitro. The HT-29 adenocarcinoma cell line was used to elucidate its pro-apoptotic activities. Flow cytometry and fluorescent microscopy were performed to assess cell cycle arrest and the accumulation of reactive oxygen species (ROS). The mRNA and hormone levels of arachidonate acid pathways were studied via quantitative reverse transcription PCR (qRT-PCR) and ELISA. The 50% growth inhibitory effect (GI50) of the IMP extract on HT-29 was measured with a value of 14.5 µg/ml. Immuno-blot and caspase-3/7 activity assay showed the pro-apoptotic effect of IMP on the activation of caspase cascade. G2/M arrest was observed via flow cytometry. The ROS activity was modulated by the IMP extraction a concentration-dependent manner in HT-29 cells. The IMP extract increased PGE2 and PGF2α levels qRT-PCR revealed that transcripts of rate-limiting PGE2- and PGF2α-biosynthetic enzymes - COX-1, mPGES1 and AKR1C3 were notably up-regulated. Among the prostanoid receptors, EP1 and FP transcripts were up-regulated while EP4 transcripts decreased. The findings suggest that the proliferative effect of PGE2, which is generally believed to associate with heightened DNA synthesis and cross-talk with MAPK pathways, is likely triggered by the pro-apoptotic or -oxidative effects exerted by IMP extract in HT-29 cells. Concurring with this notion, indomethacin (COX-1/2-inhibitor) was

  6. Promotion of adipogenesis by an EP2 receptor agonist via stimulation of angiogenesis in pulmonary emphysema.

    Science.gov (United States)

    Tsuji, Takao; Yamaguchi, Kazuhiro; Kikuchi, Ryota; Itoh, Masayuki; Nakamura, Hiroyuki; Nagai, Atsushi; Aoshiba, Kazutetsu

    2014-08-01

    Body weight loss is a common manifestation in patients with chronic obstructive pulmonary disease (COPD), particularly those with severe emphysema. Adipose angiogenesis is a key mediator of adipogenesis and use of pro-angiogenic agents may serve as a therapeutic option for lean COPD patients. Since angiogenesis is stimulated by PGE2, we examined whether ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, might promote adipose angiogenesis and adipogenesis in a murine model of elastase-induced pulmonary emphysema (EIE mice). Mice were intratracheally instilled with elastase or saline, followed after 4 weeks by intraperitoneal administration of ONO-AE1-259 for 4 weeks. The subcutaneous adipose tissue (SAT) weight decreased in the EIE mice, whereas in the EIE mice treated with ONO-AE1-259, the SAT weight was largely restored, which was associated with significant increases in SAT adipogenesis, angiogenesis, and VEGF protein production. In contrast, ONO-AE1-259 administration induced no alteration in the weight of the visceral adipose tissue. These results suggest that in EIE mice, ONO-AE1-259 stimulated adipose angiogenesis possibly via VEGF production, and thence, adipogenesis. Our data pave the way for the development of therapeutic interventions for weight loss in emphysema patients, e.g., use of pro-angiogenic agents targeting the adipose tissue vascular component. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Code comparison results for the loft LP-FP-2 experiment

    International Nuclear Information System (INIS)

    Merilo, M.; Mecham, D.C.

    1991-01-01

    Computer code calculations are compared with thermal hydraulic and fission product release, transport, and deposition data obtained from the OECD-LOFT LP-FP-2 experiment. Except for the MAAP code, which is a fully integrated severe accident code, the thermalhydraulic and fission product behavior were calculated with different codes. Six organizations participated in the thermal hydraulic portion of the code comparison exercise. These calculations were performed with RELAP 5, SCDAP/RELAP 5, and MAAP. The comparisons show generally well developed capabilities to determine the thermal-hydraulic conditions during the early stages of a severe core damage accident. Four participants submitted detailed fission product behavior calculations. Except for MAAP, as stated previously, the fission product inventory, core damage, fission product release, transport and deposition were calculated independently with different codes. Much larger differences than observed for the thermalhydraulic comparison were evident. The fission product inventory calculations were generally in good agreement with each other. Large differences were observed for release fractions and amounts of deposition. Net release calculations from the primary system were generally accurate within a factor of two or three for the more important fission products

  8. Prostaglandin F2alpha elevates blood pressure and promotes atherosclerosis

    DEFF Research Database (Denmark)

    Yu, Ying; Lucitt, Margaret B; Stubbe, Jane

    2009-01-01

    that exhibit mild polyuria and polydipsia. Atherogenesis is retarded by deletion of the FP, despite the absence of detectable receptor expression in aorta or in atherosclerotic lesions in Ldlr KOs. Although vascular TNF(alpha), inducible nitric oxide enzyme and TGF(beta) are reduced and lesional macrophages...... are depleted in the FP/Ldlr double KOs, this result reflects the reduction in lesion burden, as the FP is not expressed on macrophages and its deletion does not alter macrophage cytokine generation. Blockade of the FP offers an approach to the treatment of hypertension and its attendant systemic vascular...

  9. Targeted drugs for pulmonary arterial hypertension: a network meta-analysis of 32 randomized clinical trials

    Directory of Open Access Journals (Sweden)

    Gao XF

    2017-05-01

    Full Text Available Xiao-Fei Gao,1 Jun-Jie Zhang,1,2 Xiao-Min Jiang,1 Zhen Ge,1,2 Zhi-Mei Wang,1 Bing Li,1 Wen-Xing Mao,1 Shao-Liang Chen1,2 1Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 2Department of Cardiology, Nanjing Heart Center, Nanjing, People’s Republic of China Background: Pulmonary arterial hypertension (PAH is a devastating disease and ultimately leads to right heart failure and premature death. A total of four classical targeted drugs, prostanoids, endothelin receptor antagonists (ERAs, phosphodiesterase 5 inhibitors (PDE-5Is, and soluble guanylate cyclase stimulator (sGCS, have been proved to improve exercise capacity and hemodynamics compared to placebo; however, direct head-to-head comparisons of these drugs are lacking. This network meta-analysis was conducted to comprehensively compare the efficacy of these targeted drugs for PAH.Methods: Medline, the Cochrane Library, and other Internet sources were searched for randomized clinical trials exploring the efficacy of targeted drugs for patients with PAH. The primary effective end point of this network meta-analysis was a 6-minute walk distance (6MWD.Results: Thirty-two eligible trials including 6,758 patients were identified. There was a statistically significant improvement in 6MWD, mean pulmonary arterial pressure, pulmonary vascular resistance, and clinical worsening events associated with each of the four targeted drugs compared with placebo. Combination therapy improved 6MWD by 20.94 m (95% confidence interval [CI]: 6.94, 34.94; P=0.003 vs prostanoids, and 16.94 m (95% CI: 4.41, 29.47; P=0.008 vs ERAs. PDE-5Is improved 6MWD by 17.28 m (95% CI: 1.91, 32.65; P=0.028 vs prostanoids, with a similar result with combination therapy. In addition, combination therapy reduced mean pulmonary artery pressure by 3.97 mmHg (95% CI: -6.06, -1.88; P<0.001 vs prostanoids, 8.24 mmHg (95% CI: -10.71, -5.76; P<0.001 vs ERAs, 3.38 mmHg (95% CI: -6.30, -0.47; P=0.023 vs

  10. A novel FbFP-based biosensor toolbox for sensitive in vivo determination of intracellular pH.

    Science.gov (United States)

    Rupprecht, Christian; Wingen, Marcus; Potzkei, Janko; Gensch, Thomas; Jaeger, Karl-Erich; Drepper, Thomas

    2017-09-20

    The intracellular pH is an important modulator of various bio(techno)logical processes such as enzymatic conversion of metabolites or transport across the cell membrane. Changes of intracellular pH due to altered proton distribution can thus cause dysfunction of cellular processes. Consequently, accurate monitoring of intracellular pH allows elucidating the pH-dependency of (patho)physiological and biotechnological processes. In this context, genetically encoded biosensors represent a powerful tool to determine intracellular pH values non-invasively and with high spatiotemporal resolution. We have constructed a toolbox of novel genetically encoded FRET-based pH biosensors (named Fluorescence Biosensors for pH or FluBpH) that utilizes the FMN-binding fluorescent protein EcFbFP as donor domain. In contrast to many fluorescent proteins of the GFP family, EcFbFP exhibits a remarkable tolerance towards acidic pH (pK a ∼3.2). To cover the broad range of physiologically relevant pH values, three EYFP variants exhibiting pK a values of 5.7, 6.1 and 7.5 were used as pH-sensing FRET acceptor domains. The resulting biosensors FluBpH 5.7, FluBpH 6.1 and FluBpH 7.5 were calibrated in vitro and in vivo to accurately evaluate their pH indicator properties. To demonstrate the in vivo applicability of FluBpH, changes of intracellular pH were ratiometrically measured in E. coli cells during acid stress. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Implementation of the European multicentre database of healthy controls for [123I]FP-CIT SPECT increases diagnostic accuracy in patients with clinically uncertain parkinsonian syndromes

    International Nuclear Information System (INIS)

    Albert, Nathalie L.; Unterrainer, Marcus; Xiong, Guoming; Bartenstein, Peter; Koch, Walter; Diemling, Markus; Varrone, Andrea; Dickson, John C.; Tossici-Bolt, Livia; Sera, Terez; Asenbaum, Susanne; Booij, Jan; Kapucu, L. Oezlem A.; Kluge, Andreas; Ziebell, Morten; Darcourt, Jacques; Nobili, Flavio; Pagani, Marco; Sabri, Osama; Hesse, Swen; Borght, Thierry vander; Laere, Koen van; Tatsch, Klaus; La Fougere, Christian

    2016-01-01

    Even though [ 123 I]FP-CIT SPECT provides high accuracy in detecting nigrostriatal cell loss in neurodegenerative parkinsonian syndromes (PS), some patients with an inconclusive diagnosis remain. We investigated whether the diagnostic accuracy in patients with clinically uncertain PS with previously inconclusive findings can be improved by the use of iterative reconstruction algorithms and an improved semiquantitative evaluation which additionally implemented a correction algorithm for patient age and gamma camera dependency (EARL-BRASS; Hermes Medical Solutions, Sweden). We identified 101 patients with inconclusive findings who underwent an [ 123 I]FP-CIT SPECT between 2003 and 2010 as part of the diagnostic process of suspected PS at the University of Munich, and re-evaluated these scans using iterative reconstruction algorithms and the new corrected EARL-BRASS. Clinical follow-up was obtained in 62 out of the 101 patients and constituted the gold standard for the re-evaluation to assess the possible improvement in diagnostic accuracy. Clinical follow-up confirmed the diagnosis of PS in 11 of the 62 patients. In patients in whom both visual and semiquantitative analysis showed concordant findings (48 patients), a high negative predictive value (93 %), positive predictive value (100 %) and accuracy (94 %) were found, and thus a correct diagnosis was obtained in 45 of the 48 patients. Among the 14 patients with discordant findings, the additional semiquantitative analysis correctly identified all five of nine patients patients without PS by nonpathological semiquantitative findings in visually pathological or inconclusive scans. In contrast, four of the remaining five patients with decreased semiquantitative values but visually normal scans did not show a PS during follow-up. The age-corrected and camera-corrected mode of evaluation using EARL-BRASS provided a notable improvement in the diagnostic accuracy of [ 123 I]FP-CIT SPECT in PS patients with previously

  12. The FP4026 Research Database on the fundamental period of RC infilled frame structures.

    Science.gov (United States)

    Asteris, Panagiotis G

    2016-12-01

    The fundamental period of vibration appears to be one of the most critical parameters for the seismic design of buildings because it strongly affects the destructive impact of the seismic forces. In this article, important research data (entitled FP4026 Research Database (Fundamental Period-4026 cases of infilled frames) based on a detailed and in-depth analytical research on the fundamental period of reinforced concrete structures is presented. In particular, the values of the fundamental period which have been analytically determined are presented, taking into account the majority of the involved parameters. This database can be extremely valuable for the development of new code proposals for the estimation of the fundamental period of reinforced concrete structures fully or partially infilled with masonry walls.

  13. The FP4026 Research Database on the fundamental period of RC infilled frame structures

    Directory of Open Access Journals (Sweden)

    Panagiotis G. Asteris

    2016-12-01

    Full Text Available The fundamental period of vibration appears to be one of the most critical parameters for the seismic design of buildings because it strongly affects the destructive impact of the seismic forces. In this article, important research data (entitled FP4026 Research Database (Fundamental Period-4026 cases of infilled frames based on a detailed and in-depth analytical research on the fundamental period of reinforced concrete structures is presented. In particular, the values of the fundamental period which have been analytically determined are presented, taking into account the majority of the involved parameters. This database can be extremely valuable for the development of new code proposals for the estimation of the fundamental period of reinforced concrete structures fully or partially infilled with masonry walls.

  14. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sojin; Jin, Zhenhua; Lee, Goeun [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Park, Yong Seek; Park, Cheung-Seog [Department of Microbiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Jin, Young-Ho, E-mail: jinyh@khu.ac.kr [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of)

    2015-01-02

    Highlights: • Prostaglandin E2 (PGE{sub 2}) effect was tested on visceral afferent neurons. • PGE{sub 2} did not evoke response but potentiated serotonin (5-HT) currents up to 167%. • PGE{sub 2}-induced potentiation was blocked by E-prostanoid type 4 receptors antagonist. • PGE{sub 2} effect on 5-HT response was also blocked by protein kinase A inhibitor KT5720. • Thus, PGE{sub 2} modulate visceral afferent neurons via synergistic signaling with 5-HT. - Abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E{sub 2} (PGE{sub 2}) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE{sub 2} induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE{sub 2} effect on visceral afferent sensory neurons of the rat. Interestingly, PGE{sub 2} itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE{sub 2}-induced potentiation were blocked by a selective E-prostanoid type4 (EP{sub 4}) receptors antagonist, L-161,982, but type1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE{sub 2} effects. PGE{sub 2} induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE{sub 2} potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin

  15. Flavin mononucleotide (FMN)-based fluorescent protein (FbFP) as reporter for gene expression in the anaerobe Bacteroides fragilis.

    Science.gov (United States)

    Lobo, Leandro A; Smith, Charles J; Rocha, Edson R

    2011-04-01

    In this study, we show the expression of flavin mononucleotide-based fluorescent protein (FbFP) BS2 as a marker for gene expression in the opportunistic human anaerobic pathogen Bacteroides fragilis. Bacteroides fragilis 638R strain carrying osu∷bs2 constructs showed inducible fluorescence following addition of maltose anaerobically compared with nonfluorescent cells under glucose-repressed conditions. Bacteria carrying ahpC∷bs2 or dps∷bs2 constructs were fluorescent following induction by oxygen compared with nonfluorescent cells from the anaerobic control cultures. In addition, when these transcriptional fusion constructs were mobilized into B. fragilis IB263, a constitutive peroxide response strain, fluorescent BS2, was detected in both anaerobic and aerobic cultures, confirming the unique properties of the FbFP BS2 to yield fluorescent signal in B. fragilis in the presence and in the absence of oxygen. Moreover, intracellular expression of BS2 was also detected when cell culture monolayers of J774.1 macrophages were incubated with B. fragilis ahpC∷bs2 or dps∷bs2 strains within an anaerobic chamber. This suggests that ahpC and dps are induced following internalization by macrophages. Thus, we show that BS2 is a suitable tool for the detection of gene expression in obligate anaerobic bacteria in in vivo studies. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  16. Performance of 6FDA–6FpDA polyimide for propylene/propane separations

    KAUST Repository

    Das, Mita

    2010-12-01

    This work addresses the challenges faced by previous researchers with 6FDA-6FpDA polyimide for propylene/propane separations due to plasticization. A study of film annealing temperature is reported to optimize plasticization suppression in elevated temperature permeation on properly annealed dense films made with high molecular weight polymer. A detailed analysis of pure and mixed gas results using different permeability models is shown in this work. The annealing effects in terms of plasticization suppression and permeability and selectivity changes are discussed in detail. According to our best knowledge, this is for the first time plasticization suppression for propylene/propane has been reported with any polyimide dense film membrane. Results of pure gas sorption experiments using a pressure decay method with un-annealed and annealed films are discussed and used to analyze the permeation data using the dual-mode model. Mixed gas permeation results also are explained with dual mode and bulk flow transport models. © 2010 Elsevier B.V.

  17. Do CSF levels of t-Tau, p-Tau and β1-42 amyloid correlate with dopaminergic system impairment in patients with a clinical diagnosis of Parkinson disease? A 123I-FP-CIT study in the early stages of the disease

    International Nuclear Information System (INIS)

    Chiaravalloti, Agostino; Fiorentini, Alessandro; Lacanfora, Annamaria; Stefani, Alessandro; Stanzione, Paolo; Schillaci, Orazio

    2014-01-01

    To investigate the relationships among cerebrospinal fluid (CSF) levels of t-Tau, p-Tau and Aβ 1-42 amyloid peptide and 123 I-FP-CIT uptake. The study included 58 subjects (31 men and 27 women, age 67 ± 9 years) with a clinical diagnosis of Parkinson disease diagnosed according to the United Kingdom Parkinson Disease Society Brain Bank criteria. All subjects underwent a CSF assay 28 ± 3 days before 123 I-FP-CIT SPECT scanning. The relationships were evaluated by means of linear regression analysis and Pearson correlation. Striatal 123 I-FP-CIT was positively related to both t-Tau and p-Tau CSF values with low levels of t-Tau and p-Tau being related to a low uptake of 123 I-FP-CIT. In particular, differences with higher statistical significance were found for the striatum between the contralateral side and the side mainly affected on clinical examination (P 1-42 amyloid peptide and 123 I-FP-CIT binding. The results of our study suggest that the presynaptic dopaminergic system is more involved in Parkinson disease patients with lower t-Tau and p-Tau CSF values while values of Aβ 1-42 amyloid peptide seems not to be related to nigrostriatal degeneration in our series. (orig.)

  18. European multicentre database of healthy controls for [123I]FP-CIT SPECT (ENC-DAT): age-related effects, gender differences and evaluation of different methods of analysis

    International Nuclear Information System (INIS)

    Varrone, Andrea; Dickson, John C.; Tossici-Bolt, Livia; Sera, Terez; Asenbaum, Susanne; Booij, Jan; Kapucu, Ozlem L.; Kluge, Andreas; Knudsen, Gitte M.; Koulibaly, Pierre Malick; Nobili, Flavio; Pagani, Marco; Sabri, Osama; Borght, Thierry vander; Laere, Koen van; Tatsch, Klaus

    2013-01-01

    Dopamine transporter (DAT) imaging with [ 123 I]FP-CIT (DaTSCAN) is an established diagnostic tool in parkinsonism and dementia. Although qualitative assessment criteria are available, DAT quantification is important for research and for completion of a diagnostic evaluation. One critical aspect of quantification is the availability of normative data, considering possible age and gender effects on DAT availability. The aim of the European Normal Control Database of DaTSCAN (ENC-DAT) study was to generate a large database of [ 123 I]FP-CIT SPECT scans in healthy controls. SPECT data from 139 healthy controls (74 men, 65 women; age range 20 - 83 years, mean 53 years) acquired in 13 different centres were included. Images were reconstructed using the ordered-subset expectation-maximization algorithm without correction (NOACSC), with attenuation correction (AC), and with both attenuation and scatter correction using the triple-energy window method (ACSC). Region-of-interest analysis was performed using the BRASS software (caudate and putamen), and the Southampton method (striatum). The outcome measure was the specific binding ratio (SBR). A significant effect of age on SBR was found for all data. Gender had a significant effect on SBR in the caudate and putamen for the NOACSC and AC data, and only in the left caudate for the ACSC data (BRASS method). Significant effects of age and gender on striatal SBR were observed for all data analysed with the Southampton method. Overall, there was a significant age-related decline in SBR of between 4 % and 6.7 % per decade. This study provides a large database of [ 123 I]FP-CIT SPECT scans in healthy controls across a wide age range and with balanced gender representation. Higher DAT availability was found in women than in men. An average age-related decline in DAT availability of 5.5 % per decade was found for both genders, in agreement with previous reports. The data collected in this study may serve as a reference database for

  19. Implementation of the European multicentre database of healthy controls for [{sup 123}I]FP-CIT SPECT increases diagnostic accuracy in patients with clinically uncertain parkinsonian syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Albert, Nathalie L.; Unterrainer, Marcus; Xiong, Guoming; Bartenstein, Peter; Koch, Walter [University of Munich, Department of Nuclear Medicine, Munich (Germany); Diemling, Markus [Hermes Medical Solutions, Stockholm (Sweden); Varrone, Andrea [Karolinska University Hospital, Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm (Sweden); Dickson, John C. [UCLH NHS Foundation Trust and University College, Institute of Nuclear Medicine, London (United Kingdom); Tossici-Bolt, Livia [University Hospitals Southampton NHS Trust, Department of Medical Physics, Southampton (United Kingdom); Sera, Terez [University of Szeged, Department of Nuclear Medicine and Euromedic Szeged, Szeged (Hungary); Asenbaum, Susanne [Medical University of Vienna, Department of Neurology, Vienna (Austria); Booij, Jan [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Centre, Amsterdam (Netherlands); Kapucu, L. Oezlem A. [Gazi University, Department of Nuclear Medicine, Faculty of Medicine, Ankara (Turkey); Kluge, Andreas [ABX-CRO, Dresden (Germany); Ziebell, Morten [Rigshospitalet and University of Copenhagen, Neurobiology Research Unit, Copenhagen (Denmark); Darcourt, Jacques [University of Nice-Sophia Antipolis, Nuclear Medicine Department, Centre Antoine Lacassagne, Nice (France); Nobili, Flavio [University of Genoa, Clinical Neurology Unit, Department of Neuroscience (DINOGMI), Genoa (Italy); Pagani, Marco [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Karolinska Hospital, Department of Nuclear medicine, Stockholm (Sweden); Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Hesse, Swen [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Leipzig University Medical Centre, Molecular Neuroimaging IFB Adiposity Diseases, Leipzig (Germany); Borght, Thierry vander [Universite Catholique de Louvain, Nuclear Medicine Division, Mont-Godinne Medical Center, Yvoir (Belgium); Laere, Koen van [University Hospital and K.U. Leuven, Nuclear Medicine, Leuven (Belgium); Tatsch, Klaus [Staedtisches Klinikum Karlsruhe, Department of Nuclear Medicine, Karlsruhe (Germany); La Fougere, Christian [University of Tuebingen, Division of Nuclear Medicine, Department of Radiology, Tuebingen (Germany)

    2016-07-15

    Even though [{sup 123}I]FP-CIT SPECT provides high accuracy in detecting nigrostriatal cell loss in neurodegenerative parkinsonian syndromes (PS), some patients with an inconclusive diagnosis remain. We investigated whether the diagnostic accuracy in patients with clinically uncertain PS with previously inconclusive findings can be improved by the use of iterative reconstruction algorithms and an improved semiquantitative evaluation which additionally implemented a correction algorithm for patient age and gamma camera dependency (EARL-BRASS; Hermes Medical Solutions, Sweden). We identified 101 patients with inconclusive findings who underwent an [{sup 123}I]FP-CIT SPECT between 2003 and 2010 as part of the diagnostic process of suspected PS at the University of Munich, and re-evaluated these scans using iterative reconstruction algorithms and the new corrected EARL-BRASS. Clinical follow-up was obtained in 62 out of the 101 patients and constituted the gold standard for the re-evaluation to assess the possible improvement in diagnostic accuracy. Clinical follow-up confirmed the diagnosis of PS in 11 of the 62 patients. In patients in whom both visual and semiquantitative analysis showed concordant findings (48 patients), a high negative predictive value (93 %), positive predictive value (100 %) and accuracy (94 %) were found, and thus a correct diagnosis was obtained in 45 of the 48 patients. Among the 14 patients with discordant findings, the additional semiquantitative analysis correctly identified all five of nine patients patients without PS by nonpathological semiquantitative findings in visually pathological or inconclusive scans. In contrast, four of the remaining five patients with decreased semiquantitative values but visually normal scans did not show a PS during follow-up. The age-corrected and camera-corrected mode of evaluation using EARL-BRASS provided a notable improvement in the diagnostic accuracy of [{sup 123}I]FP-CIT SPECT in PS patients with

  20. Inhaled iloprost for the treatment of pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    H. Olschewski

    2009-03-01

    Full Text Available Prostacyclin and its analogues (prostanoids are potent vasodilators, and exhibit antithrombotic, antiproliferative and anti-inflammatory properties. Pulmonary arterial hypertension (PAH is characterised by vasoconstriction, thrombosis and proliferation, and is associated with reduced synthesis of endogenous prostacyclin. This provides a strong rationale for the use of prostanoids to treat PAH, a concept that is now supported by more than two decades of clinical research and experience. Intravenous and subcutaneous prostanoids have clearly demonstrated efficacy in severe PAH, but adverse events related to the drug delivery system, systemic side-effects and tachyphylaxis have driven research into alternative prostanoid treatments. Iloprost is administered by inhalation, and thus avoids most of the systemic side-effects associated with i.v. or subcutaneous prostanoid infusion. Two randomised controlled 12-week trials in patients with PAH have demonstrated efficacy and a favourable safety profile for iloprost as monotherapy (the AIR trial and in combination with oral bosentan (STEP. Open-label uncontrolled long-term studies of inhaled iloprost therapy indicate that this treatment may improve long-term outcomes in PAH.

  1. D2 receptor genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans.

    Science.gov (United States)

    Fazio, Leonardo; Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Romano, Raffaella; Gelao, Barbara; Ursini, Gianluca; Quarto, Tiziana; Lo Bianco, Luciana; Di Giorgio, Annabella; Mancini, Marina; Popolizio, Teresa; Rubini, Giuseppe; Bertolino, Alessandro

    2011-02-14

    Pre-synaptic D2 receptors regulate striatal dopamine release and DAT activity, key factors for modulation of motor pathways. A functional SNP of DRD2 (rs1076560 G>T) is associated with alternative splicing such that the relative expression of D2S (mainly pre-synaptic) vs. D2L (mainly post-synaptic) receptor isoforms is decreased in subjects with the T allele with a putative increase of striatal dopamine levels. To evaluate how DRD2 genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans, we have investigated the association of rs1076560 with BOLD fMRI activity during a motor task. To further evaluate the relationship of this circuitry with dopamine signaling, we also explored the correlation between genotype based differences in motor brain activity and pre-synaptic striatal DAT binding measured with [(123)I] FP-CIT SPECT. Fifty healthy subjects, genotyped for DRD2 rs1076560 were studied with BOLD-fMRI at 3T while performing a visually paced motor task with their right hand; eleven of these subjects also underwent [(123)I]FP-CIT SPECT. SPM5 random-effects models were used for statistical analyses. Subjects carrying the T allele had greater BOLD responses in left basal ganglia, thalamus, supplementary motor area, and primary motor cortex, whose activity was also negatively correlated with reaction time at the task. Moreover, left striatal DAT binding and activity of left supplementary motor area were negatively correlated. The present results suggest that DRD2 genetic variation was associated with focusing of responses in the whole motor network, in which activity of predictable nodes was correlated with reaction time and with striatal pre-synaptic dopamine signaling. Our results in humans may help shed light on genetic risk for neurobiological mechanisms involved in the pathophysiology of disorders with dysregulation of striatal dopamine like Parkinson's disease. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. La explicación sociológica de la demanda y distribución del alumnado de FP

    Directory of Open Access Journals (Sweden)

    LEOPOLDO JOSÉ CABRERA RODRÍGUEZ

    1996-01-01

    Full Text Available el presente trabajo pretende cuestionar el modelo de planificacion educativa seguido desde los años sesenta hasta la actualidad, que busca el ajuste del sistema educativo a las necesidades del sistema productivo mediante acciones sobre la oferta educativa. queremos mostrar que las posibilidades de exito de este modelo son bajas porque no considera las variables sociologicas que explican la demanda y distribucion del alumnado de fp, que, por otra parte, no parecen coincidir con las peticiones de formacion del mercado de trabajo.

  3. Implementation of the European multicentre database of healthy controls for [(123)I]FP-CIT SPECT increases diagnostic accuracy in patients with clinically uncertain parkinsonian syndromes

    DEFF Research Database (Denmark)

    Albert, Nathalie L; Unterrainer, Marcus; Diemling, Markus

    2016-01-01

    PURPOSE: Even though [(123)I]FP-CIT SPECT provides high accuracy in detecting nigrostriatal cell loss in neurodegenerative parkinsonian syndromes (PS), some patients with an inconclusive diagnosis remain. We investigated whether the diagnostic accuracy in patients with clinically uncertain PS wit...

  4. NCBI nr-aa BLAST: CBRC-MLUC-01-1145 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MLUC-01-1145 ref|NP_001041562.1| prostaglandin F receptor (FP) [Canis lupus fa...miliaris] gb|AAZ53353.1| prostaglandin F2-alpha receptor [Canis lupus familiaris] NP_001041562.1 0.0 93% ...

  5. NCBI nr-aa BLAST: CBRC-CFAM-06-0037 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CFAM-06-0037 ref|NP_001041562.1| prostaglandin F receptor (FP) [Canis lupus fa...miliaris] gb|AAZ53353.1| prostaglandin F2-alpha receptor [Canis lupus familiaris] NP_001041562.1 0.0 100% ...

  6. Evaluation of a second trimester triple marker screening test for fetal status using alpha-fetoprotein (aFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE{sub 3})

    Energy Technology Data Exchange (ETDEWEB)

    Mi, Seong Young; Kim, Jong Ho; Choi, Seung Hun [Chung Ang Gil Hospital, Inchon (Korea, Republic of)

    1997-07-01

    Our purpose was to assess the utility of maternal serum triple-marker screening test using alpha-fetoprotein (aFP), human Chorionic Gonadotropin (hCG) and unconjugated Estriol (uE{sub 3}) for fetal chromosomal abnormalities. 1,767 venous blood samples (4ml) between 15 and 20 week's gestation for maternal serum screening from January to October 1996, were tested with Kodak Amerix-M triple marker radioimmunoassay kits. Risk analysis was achieved with interpretive software such as Alpha (LMS, Kodak Clinical Diagnostics). Marker levels are transformed into multiples of median (MOM), which represent an interpretation of (weight regressed) patient marker levels relative to regressed median levels for stated gestation. By multivariate anaysis, the three MOM values are combined to generate a liklihood ratio. Calculation of a patient, risk is the product of liklihood ratio and age-related risk. Risk assessment is weight for maternal age. The median values of aFP, hCG and uE{sub 3} were well correlated with gestational age, respectively (r=0.94, p=0.003; r=-0.97, p=0.029; r=0.99, p<0.001, respectively). The median value of hCG were correlated withmateral age (r=0.13, p=0.04) but those of aFP and eU{sub 3} weren't (r=-0.17, p=0.22; r=0.36, p=0.09, respectively). The values of aFP, CG and uE{sub 3} between pregnancy younger than 35 years-old (n=87) and older than that (n=1640) were 51.67{+-}27.44, vs 54.65{+-}126.36, 46.45{+-}30.08 vs 51.33{+-}38.50 and 8.01{+-}11.01 vs 6.68{+-}7.23, respectively but all of them failed to show significant differences. A second-trimester risk for trisomy 21 > or = 1:270 was considered screen positive. Patients were screen positive for trisomy 21 if aFP < or 0.7 multiples of median (MOM), hCG> or 2.1 MOM and E{sub 3} < or 0.7 MOM. Patients were screen positive for neural tube defect if aFP >2.5 MOM. The initial screen-positive rate for both Down' syndrome and neural tube defect were 1.46% (26/1767); 0.73% (13/1767) with each other

  7. NCBI nr-aa BLAST: CBRC-ETEL-01-0643 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-ETEL-01-0643 ref|NP_001041562.1| prostaglandin F receptor (FP) [Canis lupus fa...miliaris] gb|AAZ53353.1| prostaglandin F2-alpha receptor [Canis lupus familiaris] NP_001041562.1 1e-131 95% ...

  8. NCBI nr-aa BLAST: CBRC-FCAT-01-0019 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-FCAT-01-0019 ref|NP_001041562.1| prostaglandin F receptor (FP) [Canis lupus fa...miliaris] gb|AAZ53353.1| prostaglandin F2-alpha receptor [Canis lupus familiaris] NP_001041562.1 1e-121 96% ...

  9. NCBI nr-aa BLAST: CBRC-GACU-08-0023 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GACU-08-0023 ref|NP_001041562.1| prostaglandin F receptor (FP) [Canis lupus fa...miliaris] gb|AAZ53353.1| prostaglandin F2-alpha receptor [Canis lupus familiaris] NP_001041562.1 7e-91 47% ...

  10. FP-LAPW Calculations of the EFG at Cd Impurities in Rutile SnO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Errico, L. A.; Fabricius, G.; Renteria, M. [Universidad Nacional de La Plata, Instituto de Fisica La Plata (IFLP-CONICET) - Departamento de Fisica, Facultad de Ciencias Exactas (Argentina)

    2001-11-15

    We report an ab initio study of the electric-field gradient (EFG) at Cd impurities located at the cation site in the semiconductor SnO{sub 2}(rutile phase). The study was performed with the WIEN97 implementation of the FP-LAPW method. In order to simulate the diluted Cd-impurity in the SnO{sub 2} host and to calculate the electronic structure of the system we used a 72-atoms super-cell, studying the relaxation introduced by the impurity in the lattice. The free-relaxation process performed shows that the relaxations of the oxygen nearest-neighbors of the impurity are not isotropic. Our prediction for the EFG tensor are compared with experimental results and point-charge model predictions.

  11. Molecular Cloning and Characterization of Four Genes Encoding Ethylene Receptors Associated with Pineapple (Ananas comosus L.) Flowering.

    Science.gov (United States)

    Li, Yun-He; Wu, Qing-Song; Huang, Xia; Liu, Sheng-Hui; Zhang, Hong-Na; Zhang, Zhi; Sun, Guang-Ming

    2016-01-01

    Exogenous ethylene, or ethephon, has been widely used to induce pineapple flowering, but the molecular mechanism behind ethephon induction is still unclear. In this study, we cloned four genes encoding ethylene receptors (designated AcERS1a, AcERS1b, AcETR2a, and AcETR2b). The 5' flanking sequences of these four genes were also cloned by self-formed adaptor PCR and SiteFinding-PCR, and a group of putative cis-acting elements was identified. Phylogenetic tree analysis indicated that AcERS1a, AcERS1b, AcETR2a, and AcETR2b belonged to the plant ERS1s and ETR2/EIN4-like groups. Quantitative real-time PCR showed that AcETR2a and AcETR2b (subfamily 2) were more sensitive to ethylene treatment compared with AcERS1a and AcERS1b (subfamily 1). The relative expression of AcERS1b, AcETR2a, and AcETR2b was significantly increased during the earlier period of pineapple inflorescence formation, especially at 1-9 days after ethylene treatment (DAET), whereas AcERS1a expression changed less than these three genes. In situ hybridization results showed that bract primordia (BP) and flower primordia (FP) appeared at 9 and 21 DAET, respectively, and flowers were formed at 37 DAET. AcERS1a, AcERS1b, AcETR2a, and AcETR2b were mainly expressed in the shoot apex at 1-4 DAET; thereafter, with the appearance of BP and FP, higher expression of these genes was found in these new structures. Finally, at 37 DAET, the expression of these genes was mainly focused in the flower but was also low in other structures. These findings indicate that these four ethylene receptor genes, especially AcERS1b, AcETR2a, and AcETR2b, play important roles during pineapple flowering induced by exogenous ethephon.

  12. Regulation of Expression of Renal Organic Anion Transporters OAT1 and OAT3 in a Model of Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Christina Preising

    2015-08-01

    Full Text Available Background: Recently, we gained evidence that impairment of rOat1 and rOat3 expression induced by ischemic acute kidney injury (AKI is mediated by COX metabolites and this suppression might be critically involved in renal damage. Methods: (i Basolateral organic anion uptake into proximal tubular cells after model ischemia and reperfusion (I/R was investigated by fluorescein uptake. The putative promoter sequences from hOAT1 (SLC22A6 and hOAT3 (SCL22A8 were cloned into a reporter plasmid, transfected into HEK cells and (ii transcriptional activity was determined after model ischemia and reperfusion as a SEAP reporter gen assay. Inhibitors or antagonists were applied with the beginning of reperfusion. Results: By using inhibitors of PKA (H89 and PLC (U73122, antagonists of E prostanoid receptor type 2 (AH6809 and type 4 (L161,982, we gained evidence that I/R induced down regulation of organic anion transport is mediated by COX1 metabolites via E prostanoid receptor type 4. The latter signaling was confirmed by application of butaprost (EP2 agonist or TCS2510 (EP4 agonist to control cells. In brief, the latter signaling was verified for the transcriptional activity in the reporter gen assay established. Therein, selective inhibitors for COX1 (SC58125 and COX2 (SC560 were also applied. Conclusion: Our data show (a that COX1 metabolites are involved in the regulation of renal organic anion transport(ers after I/R via the EP4 receptor and (b that this is due to transcriptional regulation of the respective transporters. As the promoter sequences cloned were of human origin and expressed in a human renal epithelial cell line we (c hypothesize that the regulatory mechanisms described after I/R is meaningful for humans as well.

  13. Identification of JAK2 as a mediator of FIP1L1-PDGFRA-induced eosinophil growth and function in CEL.

    Directory of Open Access Journals (Sweden)

    Bin Li

    Full Text Available The Fip1-like1 (FIP1L1-platelet-derived growth factor receptor alpha fusion gene (F/P arising in the pluripotent hematopoietic stem cell (HSC,causes 14% to 60% of patients with hypereosinophilia syndrome (HES. These patients, classified as having F/P (+ chronic eosinophilic leukemia (CEL, present with clonal eosinophilia and display a more aggressive disease phenotype than patients with F/P (- HES patients. The mechanisms underlying predominant eosinophil lineage targeting and the cytotoxicity of eosinophils in this leukemia remain unclear. Given that the Janus tyrosine kinase (JAK/signal transducers and activators of transcription (Stat signaling pathway is key to cytokine receptor-mediated eosinophil development and activated Stat3 and Stat5 regulate the expression of genes involved in F/P malignant transformation, we investigated whether and how JAK proteins were involved in the pathogenesis of F/P-induced CEL. F/P activation of JAK2, Stat3 and Stat5, were confirmed in all the 11 F/P (+ CEL patients examined. In vitro inhibition of JAK2 in EOL-1, primary F/P(+ CEL cells (PC and T674I F/P Imatinib resistant cells(IR by either JAK2-specific short interfering RNA (siRNA or the tryphostin derivative AG490(AG490, significantly reduced cellular proliferation and induced cellular apoptosis. The F/P can enhance the IL-5-induced JAK2 activation, and further results indicated that JAK2 inhibition blocked IL-5-induced cellular migration and activation of the EOL-1 and PC cells in vitro. F/P-stimulation of the JAK2 suppressed cells led to a significantly reduction in Stat3 activation, but relatively normal induction of Stat5 activation. Interestingly, JAK2 inhibition also reduced PI3K, Akt and NF-κB activity in a dose-dependent manner, and suppressed expression levels of c-Myc and Survivin. These results strongly suggest that JAK2 is activated by F/P and is required for F/P stimulation of cellular proliferation and infiltration, possibly through

  14. Do CSF levels of t-Tau, p-Tau and β{sub 1-42} amyloid correlate with dopaminergic system impairment in patients with a clinical diagnosis of Parkinson disease? A {sup 123}I-FP-CIT study in the early stages of the disease

    Energy Technology Data Exchange (ETDEWEB)

    Chiaravalloti, Agostino; Fiorentini, Alessandro; Lacanfora, Annamaria [University Tor Vergata, Department of Biomedicine and Prevention, Rome (Italy); Stefani, Alessandro [University Tor Vergata, Department of Neurosciences, Rome (Italy); IRCCS Santa Lucia, Rome (Italy); Stanzione, Paolo [University Tor Vergata, Department of Neurosciences, Rome (Italy); Schillaci, Orazio [University Tor Vergata, Department of Biomedicine and Prevention, Rome (Italy); IRCCS Neuromed, Pozzilli (Italy)

    2014-11-15

    To investigate the relationships among cerebrospinal fluid (CSF) levels of t-Tau, p-Tau and Aβ{sub 1-42} amyloid peptide and {sup 123}I-FP-CIT uptake. The study included 58 subjects (31 men and 27 women, age 67 ± 9 years) with a clinical diagnosis of Parkinson disease diagnosed according to the United Kingdom Parkinson Disease Society Brain Bank criteria. All subjects underwent a CSF assay 28 ± 3 days before {sup 123}I-FP-CIT SPECT scanning. The relationships were evaluated by means of linear regression analysis and Pearson correlation. Striatal {sup 123}I-FP-CIT was positively related to both t-Tau and p-Tau CSF values with low levels of t-Tau and p-Tau being related to a low uptake of {sup 123}I-FP-CIT. In particular, differences with higher statistical significance were found for the striatum between the contralateral side and the side mainly affected on clinical examination (P < 0.001). No significant relationships were found between Aβ{sub 1-42} amyloid peptide and {sup 123}I-FP-CIT binding. The results of our study suggest that the presynaptic dopaminergic system is more involved in Parkinson disease patients with lower t-Tau and p-Tau CSF values while values of Aβ{sub 1-42} amyloid peptide seems not to be related to nigrostriatal degeneration in our series. (orig.)

  15. Photon and decay data libraries for ORIGEN2 code based on JENDL FP decay data file 2000

    CERN Document Server

    Katakura, J I

    2002-01-01

    Photon and decay data libraries for the ORIGEN2 code have been updated by using JENDL FP Decay Data File 2000 (JENDL/FPD-00). As for the decay data, half-lives, branching ratios and recoverable energy values have been replaced with those of the JENDL/FPD-00 file. The data of the photon library has been also replaced with those of the JENDL/FPD-00 file in which photon data of the nuclides without measured data are calculated with a theoretical method. Using the updated photon library, the calculation of photon spectrum at a short time after fission event is able to be made.

  16. Automatic on-line detection system design research on internal defects of metal materials based on optical fiber F-P sensing technology

    Science.gov (United States)

    Xia, Liu; Shan, Ning; Chao, Ban; Caoshan, Wang

    2016-10-01

    Metal materials have been used in aerospace and other industrial fields widely because of its excellent characteristics, so its internal defects detection is very important. Ultrasound technology is used widely in the fields of nondestructive detection because of its excellent characteristic. But the conventional detection instrument for ultrasound, which has shortcomings such as low intelligent level and long development cycles, limits its development. In this paper, the theory of ultrasound detection is analyzed. A computational method of the defects distributional position is given. The non-contact type optical fiber F-P interference cavity structure is designed and the length of origin cavity is given. The real-time on-line ultrasound detecting experiment devices for internal defects of metal materials is established based on the optical fiber F-P sensing system. The virtual instrument of automation ultrasound detection internal defects is developed based on LabVIEW software and the experimental study is carried out. The results show that this system can be used in internal defect real-time on-line locating of engineering structures effectively. This system has higher measurement precision. Relative error is 6.7%. It can be met the requirement of engineering practice. The system is characterized by simple operation, easy realization. The software has a friendly interface, good expansibility, and high intelligent level.

  17. The significance of 18F-FP-β-CIT dopamine transporter PET imaging in early diagnosis of Parkinson's disease

    International Nuclear Information System (INIS)

    Wang Jian; Jiang Yuping; Guo Liping; Yang Liqin; Wu Jianjun; Ding Zhengtong; Guan Yihui; Zhao Jun; Xiang Jingde; Chen Zhengping; Su Huilin

    2003-01-01

    Objective: To evaluate the 18 F-N-3-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ( 18 F-FP-β-CIT) dopamine transporter (DAT) PET imaging in diagnosing Parkinson's disease with early stage and assessing the severity of their disability. Methods: 4 healthy controls, 21 parkinsonian patients with early stage and 10 parkinsonian patients with advanced stage were studied, the ratio of [ region of interest (ROI)-cerebellum]/cerebellum was measured and compared. The correlation between DAT binding in striatum and unified Parkinson's disease rating scale (UPDRS) motor scores was also determined. Results: In patients with early stage (Hoehn and Yahr stage I-II) , the DAT binding uptake in the caudate, anterior putamen and posterior putamen was significantly reduced to 71.8%, 43.8% and 23.6% of the control value respectively, and more pronounced reduction of the uptake was found in the striatum contralateral to the predominant symptoms. Compared with age-matched controls, there was a significant reduction of DAT binding in the ipsilateral (preclinical) striatum of hemi-parkinsonian patients with Hoehn and Yahr stage 1 or 1.5. In the patients with advanced stage, the corresponding figure were further reduced to 51.9%, 31.8%, 15.8%. The DAT binding uptake in striatum of all parkinsonian patients showed significantly negative correlation with UPDRS motor scores, especially in the subregion of posterior putamen. Conclusion: 18 F-FP-β-CIT DAT PET imaging is helpful in diagnosing Parkinson's disease with early stage and assessing the severity of their disability

  18. The discriminating nature of dopamine transporter image in parkinsonism: the competency of dopaminergic transporter imaging in differential diagnosis of parkinsonism 123I-FP-CIT SPECT study

    International Nuclear Information System (INIS)

    Kim, Bom Sahn; Jang, Sung June; Eo, Jae Seon; Park, Eun Kyung; Kim, Yu Kyeong; Kim, Jong Min; Lee, Won Woo; Kim, Sang Eun

    2007-01-01

    The aim of this study was to evaluate the discriminating nature of 123 I-FP-CIT SPECT in patients with parkinsonism. 123 I-FP-CIT SPECT images acquired from the 18 normal controls; NC (60.4 ± 10.0 yr) and 237 patients with parkinsonism (65.9 ± 9.2 yr) were analyzed. From spatially normalized images, regional counts of the caudate, putamen, and occipital lobe were obtained using region of interest method. Binding potential (BP) was calculated with the ratio of specific to nonspecific binding activity at equilibrium. Additionally, the BP ratio of putamen to caudate (PCR) and asymmetric index (ASI) were measured. BPs of NC (3.37 ± 0.57, 3.10± 0.41, 3.23 ± 0.48 for caudate, putamen, whole striatum, respectively) had no significant difference with those of essential tremor; ET (3.31 ± 0.64, 3.06 ± 0.61, 3.14 ± 0.63) and Alzheimer's disease; AD (3.33 ± 0.60, 3.29 ± 0.79, 3.31 ± 0.70), but were higher than those of Parkinson's disease; PD (1.92 ± 0.74, 1.39 ±0.68, 1.64 ± 0.68), multiple system atrophy; MSA (2.36 ± 1.07, 2.16 ± 0.91, 2.26 ± 0.96), and dementia with Lewy body; DLB (1.95± 0.72, 1.64 ± 0.65, 1.79 ± 0.66)(ρ 123 I-FP-CIT SPECT was a good value in differential diagnosis of parkinsonism

  19. Cost-Effectiveness Analysis of Different Sequences of the Use of Epidermal Growth Factor Receptor Inhibitors for Wild-Type KRAS Unresectable Metastatic Colorectal Cancer.

    Science.gov (United States)

    Riesco-Martínez, Maria Carmen; Berry, Scott R; Ko, Yoo-Joung; Mittmann, Nicole; Giotis, Angie; Lien, Kelly; Wong, William W L; Chan, Kelvin K W

    2016-06-01

    Patients with unresectable wild-type KRAS metastatic colorectal cancer benefit from fluoropyrimidines (FP), oxaliplatin (O), irinotecan (I), bevacizumab (Bev), and epithelial growth factor receptor inhibitors (EGFRI). The most cost-effective regimen remains unclear. A Markov model was constructed to examine the costs and outcomes of three treatment strategies: strategy A (reference strategy): EGFRI monotherapy in third line ([3L]; ie, first-line [1L]: Bev + FOLFIRI [FP + I] or FOLFOX [FP + O]; second line [2L]: FOLFIRI/FOLFOX; 3L: EGFRI); strategy B: EGFRI and I in 3L (ie, 1L: Bev + FOLFIRI/FOLFOX; 2L: FOLFIRI/FOLFOX; 3L: EGFRI + I); and strategy C: EGFRI in 1L (ie, 1L: EGFRI + FOLFIRI/FOLFOX; 2L: Bev + FOLFIRI/FOLFOX; 3L: best supportive care). Efficacy data of the treatments were obtained from the literature. Health system resource use information was derived from chart review and the literature. Using Euro-QOL 5 Dimensions, utilities were obtained by surveying medical oncologists and costs from the Ontario Ministry of Health and the literature. The perspective of the Canadian public health care system was used over a 5-year time horizon with a 5% discount in 2012 Canadian dollars. All three strategies had similar efficacy, but strategy C was most expensive. The incremental cost-effectiveness ratios (ICERs) for strategies B and C compared with A were 119,623 and 3,176,591, respectively. The model was primarily driven by the acquisition cost of the drugs. Strategy B was most cost effective when the willingness-to-pay threshold was > $130,000 per quality-adjusted life-year. Sensitivity analysis showed that strategy C would be cost-effective only when the progression-free survival of EGFRI is better than Bev in 1L with hazard ratio pricing relative to Bev. Copyright © 2016 by American Society of Clinical Oncology.

  20. Silicon-Light: a European FP7 Project Aiming at High Efficiency Thin Film Silicon Solar Cells on Foil

    DEFF Research Database (Denmark)

    Soppe, W.; Haug, F.-J.; Couty, P.

    2011-01-01

    Silicon-Light is a European FP7 project, which started January 1st, 2010 and aims at development of low cost, high-efficiency thin film silicon solar cells on foil. Three main routes are explored to achieve these goals: a) advanced light trapping by implementing nanotexturization through UV Nano...... calculations of ideal nanotextures for light trapping in thin film silicon solar cells; the fabrication of masters and the replication and roll-to-roll fabrication of these nanotextures. Further, results on ITO variants with improved work function are presented. Finally, the status of cell fabrication on foils...

  1. Comparison between a dual-head and a brain-dedicated SPECT system in the measurement of the loss of dopamine transporters with [123I]FP-CIT

    International Nuclear Information System (INIS)

    Varrone, Andrea; Sansone, Valeria; Pappata, Sabina; Salvatore, Marco; Pellecchia, Maria T.; Salvatore, Elena; de Michele, Giuseppe; Filla, Alessandro; Barone, Paolo; Amboni, Marianna

    2008-01-01

    Dual-head SPECT systems are used by many clinical departments for [ 123 I]FP-CIT SPECT imaging, while triple-head or brain-dedicated systems with better imaging performance are more commonly used by research institutions. There are limited data comparing the capability of the two types of system to measure dopamine transporter (DAT) loss in vivo. The aim of this study was to compare the ability of a dual-head and a brain-dedicated SPECT system to estimate the degree of DAT loss in different movement disorders with variable nigrostriatal impairment, with [ 123 I]FP-CIT. Four patients with essential tremor, 24 with Parkinson's disease (PD), six with spinocerebellar ataxia type 2 and six controls were studied with [ 123 I]FP-CIT. SPECT scans were performed on a dual-head (E.CAM - Siemens) and subsequently on a brain-dedicated system (Ceraspect - DSI). Striatal DAT outcome measures on the E.CAM and the Ceraspect were strongly correlated and the putamen-to-caudate ratios were almost identical. Although the measured values were lower by 52 ± 25% in caudate and by 51 ± 31% in putamen on the E.CAM (p < 0.0001), the average striatal DAT decrease in each patient group compared with controls was similar for both systems. In PD patients, similar correlations (p < 0.05) were found between motor UPDRS or Hoehn and Yahr stage and striatal DAT density. Despite underestimation of striatal DAT outcome measures, the E.CAM showed similar capability as the Ceraspect in measuring the degree of nigrostriatal dopaminergic deficit and assessing the correlation between DAT outcome measures and clinical variables of PD severity and stage. (orig.)

  2. Prostaglandin E2 facilitates neurite outgrowth in a motor neuron-like cell line, NSC-34

    Directory of Open Access Journals (Sweden)

    Hiroshi Nango

    2017-10-01

    Full Text Available Prostaglandin E2 (PGE2 exerts various biological effects by binding to E-prostanoid receptors (EP1-4. Although recent studies have shown that PGE2 induces cell differentiation in some neuronal cells such as mouse DRG neurons and sensory neuron-like ND7/23 cells, it is unclear whether PGE2 plays a role in differentiation of motor neurons. In the present study, we investigated the mechanism of PGE2-induced differentiation of motor neurons using NSC-34, a mouse motor neuron-like cell line. Exposure of undifferentiated NSC-34 cells to PGE2 and butaprost, an EP2-selective agonist, resulted in a reduction of MTT reduction activity without increase the number of propidium iodide-positive cells and in an increase in the number of neurite-bearing cells. Sulprostone, an EP1/3 agonist, also significantly lowered MTT reduction activity by 20%; however, no increase in the number of neurite-bearing cells was observed within the concentration range tested. PGE2-induced neurite outgrowth was attenuated significantly in the presence of PF-0441848, an EP2-selective antagonist. Treatment of these cells with dibutyryl-cAMP increased the number of neurite-bearing cells with no effect on cell proliferation. These results suggest that PGE2 promotes neurite outgrowth and suppresses cell proliferation by activating the EP2 subtype, and that the cAMP-signaling pathway is involved in PGE2-induced differentiation of NSC-34 cells. Keywords: Prostaglandin E2, E-prostanoid receptors, Motor neuron, Neurite outgrowth, cAMP

  3. European multicentre database of healthy controls for [{sup 123}I]FP-CIT SPECT (ENC-DAT): age-related effects, gender differences and evaluation of different methods of analysis

    Energy Technology Data Exchange (ETDEWEB)

    Varrone, Andrea [Karolinska University Hospital, R5:02, Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm (Sweden); Dickson, John C. [UCLH NHS Foundation Trust and University College, Institute of Nuclear Medicine, London (United Kingdom); Tossici-Bolt, Livia [University Hospitals Southampton NHS Trust, Department of Medical Physics, Southampton (United Kingdom); Sera, Terez [University of Szeged, Department of Nuclear Medicine and Euromedic Szeged, Szeged (Hungary); Asenbaum, Susanne [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); Booij, Jan [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Centre, Amsterdam (Netherlands); Kapucu, Ozlem L. [Gazi University, Department of Nuclear Medicine, Faculty of Medicine, Ankara (Turkey); Kluge, Andreas [ABX-CRO, Dresden (Germany); Knudsen, Gitte M. [Rigshospitalet and University of Copenhagen, Neurobiology Research Unit, Copenhagen (Denmark); Koulibaly, Pierre Malick [University of Nice-Sophia Antipolis, Nuclear Medicine Department, Centre Antoine Lacassagne, Nice (France); Nobili, Flavio [University of Genoa, Clinical Neurophysiology Unit, Department of Neuroscience, Ophthalmology and Genetics, Genoa (Italy); Pagani, Marco [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Borght, Thierry vander [Universite Catholique de Louvain, Nuclear Medicine Division, Mont-Godinne Medical Center, Yvoir (Belgium); Laere, Koen van [University Hospital and K.U. Leuven, Nuclear Medicine, Leuven (Belgium); Tatsch, Klaus [Municipal Hospital of Karlsruhe Inc, Department of Nuclear Medicine, Karlsruhe (Germany)

    2013-02-15

    Dopamine transporter (DAT) imaging with [{sup 123}I]FP-CIT (DaTSCAN) is an established diagnostic tool in parkinsonism and dementia. Although qualitative assessment criteria are available, DAT quantification is important for research and for completion of a diagnostic evaluation. One critical aspect of quantification is the availability of normative data, considering possible age and gender effects on DAT availability. The aim of the European Normal Control Database of DaTSCAN (ENC-DAT) study was to generate a large database of [{sup 123}I]FP-CIT SPECT scans in healthy controls. SPECT data from 139 healthy controls (74 men, 65 women; age range 20 - 83 years, mean 53 years) acquired in 13 different centres were included. Images were reconstructed using the ordered-subset expectation-maximization algorithm without correction (NOACSC), with attenuation correction (AC), and with both attenuation and scatter correction using the triple-energy window method (ACSC). Region-of-interest analysis was performed using the BRASS software (caudate and putamen), and the Southampton method (striatum). The outcome measure was the specific binding ratio (SBR). A significant effect of age on SBR was found for all data. Gender had a significant effect on SBR in the caudate and putamen for the NOACSC and AC data, and only in the left caudate for the ACSC data (BRASS method). Significant effects of age and gender on striatal SBR were observed for all data analysed with the Southampton method. Overall, there was a significant age-related decline in SBR of between 4 % and 6.7 % per decade. This study provides a large database of [{sup 123}I]FP-CIT SPECT scans in healthy controls across a wide age range and with balanced gender representation. Higher DAT availability was found in women than in men. An average age-related decline in DAT availability of 5.5 % per decade was found for both genders, in agreement with previous reports. The data collected in this study may serve as a reference

  4. Do CSF levels of t-Tau, p-Tau and β₁₋₄₂ amyloid correlate with dopaminergic system impairment in patients with a clinical diagnosis of Parkinson disease? A ¹²³I-FP-CIT study in the early stages of the disease.

    Science.gov (United States)

    Chiaravalloti, Agostino; Stefani, Alessandro; Fiorentini, Alessandro; Lacanfora, Annamaria; Stanzione, Paolo; Schillaci, Orazio

    2014-11-01

    To investigate the relationships among cerebrospinal fluid (CSF) levels of t-Tau, p-Tau and Aβ₁₋₄₂ amyloid peptide and (123)I-FP-CIT uptake. The study included 58 subjects (31 men and 27 women, age 67 ± 9 years) with a clinical diagnosis of Parkinson disease diagnosed according to the United Kingdom Parkinson Disease Society Brain Bank criteria. All subjects underwent a CSF assay 28 ± 3 days before (123)I-FP-CIT SPECT scanning. The relationships were evaluated by means of linear regression analysis and Pearson correlation. Striatal (123)I-FP-CIT was positively related to both t-Tau and p-Tau CSF values with low levels of t-Tau and p-Tau being related to a low uptake of (123)I-FP-CIT. In particular, differences with higher statistical significance were found for the striatum that is contralateral to theside mainly affected on clinical examination (P<0.001) [corrected].No significant relationships were found between Aβ₁₋₄₂ amyloid peptide and (123)I-FP-CIT binding. The results of our study suggest that the presynaptic dopaminergic system is more involved in Parkinson disease patients with lower t-Tau and p-Tau CSF values while values of Aβ₁₋₄₂ amyloid peptide seems not to be related to nigrostriatal degeneration in our series.

  5. Selected proceedings of the FP7 International Summer School Nanotechnology: From Fundamental Research to Innovations

    CERN Document Server

    Yatsenko, Leonid; Brodin, Mikhaylo; Nanomaterials imaging techniques, surface studies, and applications

    2013-01-01

    This book presents cutting-edge research on a wide range of nanotechnology techniques and applications.  It features contributions from scientists who participated in the International Summer School “Nanotechnology: From Fundamental Research to Innovations” in Bukovel, Ukraine on August 26 – September 2, 2012 funded by the European Commission FP7 project Nanotwinning implemented by the Institute of Physics of National Academy of Sciences of Ukraine and partner institutions: University of Tartu (Estonia), European Profiles A.E. (Greece), University of Turin (Italy) and Université Pierre et Marie Curie (France).  Worldwide experts present the latest results on such key topics as microscopy of nanostructures; nanocomposites; nanostructured interfaces and surfaces; nanooptics; nanoplasmonics; and enhanced vibrational spectroscopy.  Imaging technique coverage ranges from atomic force microscopy and spectroscopy, multiphoton imagery, and laser diagnostics of nanomaterials and nanostructures, to resonance ...

  6. Long acting β2-agonist and corticosteroid restore airway glandular cell function altered by bacterial supernatant

    Directory of Open Access Journals (Sweden)

    Nawrocki-Raby Béatrice

    2010-01-01

    Full Text Available Abstract Background Staphylococcus aureus releases virulence factors (VF that may impair the innate protective functions of airway cells. The aim of this study was to determine whether a long-acting β2 adrenergic receptor agonist (salmeterol hydroxynaphthoate, Sal combined with a corticosteroid (fluticasone propionate, FP was able to regulate ion content and cytokine expression by airway glandular cells after exposure to S. aureus supernatant. Methods A human airway glandular cell line was incubated with S. aureus supernatant for 1 h and then treated with the combination Sal/FP for 4 h. The expression of actin and CFTR proteins was analyzed by immunofluorescence. Videomicroscopy was used to evaluate chloride secretion and X-ray microanalysis to measure the intracellular ion and water content. The pro-inflammatory cytokine expression was assessed by RT-PCR and ELISA. Results When the cells were incubated with S. aureus supernatant and then with Sal/FP, the cellular localisation of CFTR was apical compared to the cytoplasmic localisation in cells incubated with S. aureus supernatant alone. The incubation of airway epithelial cells with S. aureus supernatant reduced by 66% the chloride efflux that was fully restored by Sal/FP treatment. We also observed that Sal/FP treatment induced the restoration of ion (Cl and S and water content within the intracellular secretory granules of airway glandular cells and reduced the bacterial supernatant-dependent increase of pro-inflammatory cytokines IL8 and TNFα. Conclusions Our results demonstrate that treatment with the combination of a corticosteroid and a long-acting β2 adrenergic receptor agonist after bacterial infection restores the airway glandular cell function. Abnormal mucus induced by defective ion transport during pulmonary infection could benefit from treatment with a combination of β2 adrenergic receptor agonist and glucocorticoid.

  7. Reduction in camera-specific variability in [{sup 123}I]FP-CIT SPECT outcome measures by image reconstruction optimized for multisite settings: impact on age-dependence of the specific binding ratio in the ENC-DAT database of healthy controls

    Energy Technology Data Exchange (ETDEWEB)

    Buchert, Ralph; Lange, Catharina [Charite - Universitaetsmedizin Berlin, Department of Nuclear Medicine, Berlin (Germany); Kluge, Andreas; Bronzel, Marcus [ABX-CRO advanced pharmaceutical services Forschungsgesellschaft m.b.H., Dresden (Germany); Tossici-Bolt, Livia [University Hospital Southampton NHS Foundation Trust, Department of Medical Physics, Southampton (United Kingdom); Dickson, John [University College London Hospital NHS Foundation Trust, Institute of Nuclear Medicine, London (United Kingdom); Asenbaum, Susanne [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); Booij, Jan [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Centre, Amsterdam (Netherlands); Kapucu, L. Oezlem Atay [Gazi University, Department of Nuclear Medicine, Faculty of Medicine, Ankara (Turkey); Svarer, Claus [Rigshospitalet and University of Copenhagen, Neurobiology Research Unit, Copenhagen (Denmark); Koulibaly, Pierre-Malick [University of Nice-Sophia Antipolis, Nuclear Medicine Department, Centre Antoine Lacassagne, Nice (France); Nobili, Flavio [University of Genoa, Department of Neuroscience (DINOGMI), Clinical Neurology Unit, Genoa (Italy); Pagani, Marco [CNR, Institute of Cognitive Sciences and Technologies, Rome (Italy); Karolinska Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Sera, Terez [University of Szeged, Department of Nuclear Medicine and Euromedic Szeged, Szeged (Hungary); Tatsch, Klaus [Municipal Hospital of Karlsruhe Inc, Department of Nuclear Medicine, Karlsruhe (Germany); Borght, Thierry vander [CHU Namur, IREC, Nuclear Medicine Division, Universite catholique de Louvain, Yvoir (Belgium); Laere, Koen van [University Hospital and K.U. Leuven, Nuclear Medicine, Leuven (Belgium); Varrone, Andrea [Karolinska University Hospital, Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm (Sweden); Iida, Hidehiro [National Cerebral and Cardiovascular Center - Research Institute, Osaka (Japan)

    2016-07-15

    Quantitative estimates of dopamine transporter availability, determined with [{sup 123}I]FP-CIT SPECT, depend on the SPECT equipment, including both hardware and (reconstruction) software, which limits their use in multicentre research and clinical routine. This study tested a dedicated reconstruction algorithm for its ability to reduce camera-specific intersubject variability in [{sup 123}I]FP-CIT SPECT. The secondary aim was to evaluate binding in whole brain (excluding striatum) as a reference for quantitative analysis. Of 73 healthy subjects from the European Normal Control Database of [{sup 123}I]FP-CIT recruited at six centres, 70 aged between 20 and 82 years were included. SPECT images were reconstructed using the QSPECT software package which provides fully automated detection of the outer contour of the head, camera-specific correction for scatter and septal penetration by transmission-dependent convolution subtraction, iterative OSEM reconstruction including attenuation correction, and camera-specific ''to kBq/ml'' calibration. LINK and HERMES reconstruction were used for head-to-head comparison. The specific striatal [{sup 123}I]FP-CIT binding ratio (SBR) was computed using the Southampton method with binding in the whole brain, occipital cortex or cerebellum as the reference. The correlation between SBR and age was used as the primary quality measure. The fraction of SBR variability explained by age was highest (1) with QSPECT, independently of the reference region, and (2) with whole brain as the reference, independently of the reconstruction algorithm. QSPECT reconstruction appears to be useful for reduction of camera-specific intersubject variability of [{sup 123}I]FP-CIT SPECT in multisite and single-site multicamera settings. Whole brain excluding striatal binding as the reference provides more stable quantitative estimates than occipital or cerebellar binding. (orig.)

  8. SACSESS – the EURATOM FP7 project on actinide separation from spent nuclear fuels

    Directory of Open Access Journals (Sweden)

    Bourg Stéphane

    2015-12-01

    Full Text Available Recycling of actinides by their separation from spent nuclear fuel, followed by transmutation in fast neutron reactors of Generation IV, is considered the most promising strategy for nuclear waste management. Closing the fuel cycle and burning long-lived actinides allows optimizing the use of natural resources and minimizing the long-term hazard of high-level nuclear waste. Moreover, improving the safety and sustainability of nuclear power worldwide. This paper presents the activities striving to meet these challenges, carried out under the Euratom FP7 collaborative project SACSESS (Safety of Actinide Separation Processes. Emphasis is put on the safety issues of fuel reprocessing and waste storage. Two types of actinide separation processes, hydrometallurgical and pyrometallurgical, are considered, as well as related aspects of material studies, process modeling and the radiolytic stability of solvent extraction systems. Education and training of young researchers in nuclear chemistry is of particular importance for further development of this field.

  9. Extrastriatal binding of [¹²³I]FP-CIT in the thalamus and pons

    DEFF Research Database (Denmark)

    Koch, Walter; Unterrainer, Marcus; Xiong, Guoming

    2014-01-01

    extrastriatal binding (predominantly due to SERT) and its age and gender dependencies in a large cohort of healthy controls. METHODS: SPECT data from 103 healthy controls with well-defined criteria of normality acquired at 13 different imaging centres were analysed for extrastriatal binding using volumes...... error) of 8.2 ± 1.3 % for the thalamus and 6.8 ± 2.9 % for the pons was shown. CONCLUSION: The potential to evaluate extrastriatal predominant SERT binding in addition to the striatal DAT in a single imaging session was shown using a large database of [(123)I]FP-CIT scans in healthy controls. For both...... the thalamus and the pons, an age-related decline in radiotracer binding was observed. Gender effects were demonstrated for binding in the thalamus only. As a potential clinical application, the data could be used as a reference to estimate SERT occupancy in addition to nigrostriatal integrity when using [(123...

  10. Extrastriatal binding of [123I]FP-CIT in the thalamus and pons: gender and age dependencies assessed in a European multicentre database of healthy controls

    International Nuclear Information System (INIS)

    Koch, Walter; Unterrainer, Marcus; Xiong, Guoming; Bartenstein, Peter; Diemling, Markus; Varrone, Andrea; Dickson, John C.; Tossici-Bolt, Livia; Sera, Terez; Asenbaum, Susanne; Booij, Jan; Kapucu, Ozlem L.; Kluge, Andreas; Ziebell, Morten; Darcourt, Jacques; Nobili, Flavio; Pagani, Marco; Hesse, Swen; Borght, Thierry Vander; Laere, Koen van; Tatsch, Klaus; La Fougere, Christian

    2014-01-01

    Apart from binding to the dopamine transporter (DAT), [ 123 I]FP-CIT shows moderate affinity for the serotonin transporter (SERT), allowing imaging of both monoamine transporters in a single imaging session in different brain areas. The aim of this study was to systematically evaluate extrastriatal binding (predominantly due to SERT) and its age and gender dependencies in a large cohort of healthy controls. SPECT data from 103 healthy controls with well-defined criteria of normality acquired at 13 different imaging centres were analysed for extrastriatal binding using volumes of interest analysis for the thalamus and the pons. Data were examined for gender and age effects as well as for potential influence of striatal DAT radiotracer binding. Thalamic binding was significantly higher than pons binding. Partial correlations showed an influence of putaminal DAT binding on measured binding in the thalamus but not on the pons. Data showed high interindividual variation in extrastriatal binding. Significant gender effects with 31 % higher binding in women than in men were observed in the thalamus, but not in the pons. An age dependency with a decline per decade (±standard error) of 8.2 ± 1.3 % for the thalamus and 6.8 ± 2.9 % for the pons was shown. The potential to evaluate extrastriatal predominant SERT binding in addition to the striatal DAT in a single imaging session was shown using a large database of [ 123 I]FP-CIT scans in healthy controls. For both the thalamus and the pons, an age-related decline in radiotracer binding was observed. Gender effects were demonstrated for binding in the thalamus only. As a potential clinical application, the data could be used as a reference to estimate SERT occupancy in addition to nigrostriatal integrity when using [ 123 I]FP-CIT for DAT imaging in patients treated with selective serotonin reuptake inhibitors. (orig.)

  11. Effect of S-1 chemotherapy and FP chemotherapy on prognosis, imaging characteristics and serum marker levels after operation for gastric carcinoma

    Directory of Open Access Journals (Sweden)

    Qing-Hao Gong

    2016-09-01

    Full Text Available Objective: To analyze the effect of S-1 chemotherapy and FP chemotherapy on prognosis, imaging characteristics and serum marker levels after operation for gastric carcinoma. Methods: A total of 68 patients with gastric cancer who underwent radical surgery were included in the study and divided into observation group and control group patients (n=34 according to random number table. Control group received FP chemotherapy, observation group received S-1 chemotherapy, and then differences in serum tumor markers, illnessrelated factors, nutrition indexes and T cell immune function values were compared between two groups. Results: After observation group received systematic chemotherapy, serum tumor markers such as MMP-9, MMP-2, MG7-Ag, TSGF, CA72-4, CA19-9, TP and DpD as well as illness-related factors such as DKK1, MK, Leptin, Exosome and OPN were all lower than those of control group (P<0.05; nutrition and cellular immune function indexes such as TP, ALB, PA, CD4+ T and CD4+ T/ CD8+ T values were higher than those of control group and CD8+ T value was lower than that of control group (P<0.05. Conclusions: S-1 chemotherapy after operation for gastric carcinoma can inhibit the tumor activity and optimize patients’ overall condition, and it has positive clinical significance.

  12. FRET-based localization of fluorescent protein insertions within the ryanodine receptor type 1.

    Directory of Open Access Journals (Sweden)

    Shweta A Raina

    Full Text Available Fluorescent protein (FP insertions have often been used to localize primary structure elements in mid-resolution 3D cryo electron microscopic (EM maps of large protein complexes. However, little is known as to the precise spatial relationship between the location of the fused FP and its insertion site within a larger protein. To gain insights into these structural considerations, Förster resonance energy transfer (FRET measurements were used to localize green fluorescent protein (GFP insertions within the ryanodine receptor type 1 (RyR1, a large intracellular Ca(2+ release channel that plays a key role in skeletal muscle excitation contraction coupling. A series of full-length His-tagged GFP-RyR1 fusion constructs were created, expressed in human embryonic kidney (HEK-293T cells and then complexed with Cy3NTA, a His-tag specific FRET acceptor. FRET efficiency values measured from each GFP donor to Cy3NTA bound to each His tag acceptor site were converted into intermolecular distances and the positions of each inserted GFP were then triangulated relative to a previously published X-ray crystal structure of a 559 amino acid RyR1 fragment. We observed that the chromophoric centers of fluorescent proteins inserted into RyR1 can be located as far as 45 Å from their insertion sites and that the fused proteins can also be located in internal cavities within RyR1. These findings should prove useful in interpreting structural results obtained in cryo EM maps using fusions of small fluorescent proteins. More accurate point-to-point distance information may be obtained using complementary orthogonal labeling systems that rely on fluorescent probes that bind directly to amino acid side chains.

  13. MELCOR 1.8.1 Assessment: LOFT integral experiment LP-FP-2

    International Nuclear Information System (INIS)

    Kmetyk, L.N.

    1992-12-01

    The MELCOR code has been used to model experiment LP-FP-2, an important source of integral data for qualifying severe accident code predictive capabilities. This assessment analysis clearly demonstrates MELCOR's ability to fulfill a large part of its primary, intended use, the calculation of severe accidents from full-power steady-state initiation through primary-system thermal/hydraulic response and core damage to fission product release, transport and deposition. After a number of code errors were identified and corrected, few nonstandard inputs and no code problem-specific modifications were needed to provide reasonable agreement with test data in all areas considered. Code-to-code comparisons show that MELCOR does at least as well as other ''best-estimate'' (i.e., SCDAP/RELAP5) or integral (i.e., MAAP) codes in predicting the thermal/hydraulic and core responses in this large-scale, integral experiment; in fact, MELCOR and MAAP appear to give the best agreement with data, especially for clad temperature histories. Further, our code-to-code comparisons indicate that MELCOR does at least as well as ''best-estimate'' fission product codes in predicting the source term, with a number of such codes having to be run in tandem and driven by test data or other ''best-estimate'' thermal/hydraulic and core damage codes to provide results equivalent to a single, integrated MELCOR calculation

  14. Beta Decay Study of the T{sub z}=−2{sup 56}Zn Nucleus and the Determination of the Half-Lives of a Few fp-shell Nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Rubio, B., E-mail: Berta.Rubio@ific.uv.es [IFIC, CSIC-Universidad de Valencia, E-46071 Valencia (Spain); Orrigo, S.E.A. [IFIC, CSIC-Universidad de Valencia, E-46071 Valencia (Spain); Kucuk, L. [Department of Physics, Istanbul University, Istanbul (Turkey); Montaner-Pizá, A. [IFIC, CSIC-Universidad de Valencia, E-46071 Valencia (Spain); Fujita, Y. [Department of Physics, Osaka University, Toyonaka, Osaka 560-0043 (Japan); RCNP, Osaka University, Ibaraki, Osaka 567-0047 (Japan); Fujita, H. [RCNP, Osaka University, Ibaraki, Osaka 567-0047 (Japan); Blank, B. [CENBG, Université Bordeaux 1, UMR 5797 CNRS/IN2P3, BP 120, F-33175 Gradignan (France); Gelletly, W. [Department of Physics, University of Surrey, Guildford GU2 7XH, Surrey (United Kingdom); Adachi, T. [RCNP, Osaka University, Ibaraki, Osaka 567-0047 (Japan); Agramunt, J.; Algora, A. [IFIC, CSIC-Universidad de Valencia, E-46071 Valencia (Spain); Ascher, P. [CENBG, Université Bordeaux 1, UMR 5797 CNRS/IN2P3, BP 120, F-33175 Gradignan (France); Bilgier, B. [Department of Physics, Istanbul University, Istanbul (Turkey); Cáceres, L. [GANIL, CEA/DSM-CNRS/IN2P3, BP 55027, F-14076 Caen (France); Cakirli, R.B. [Department of Physics, Istanbul University, Istanbul (Turkey); France, G. de [GANIL, CEA/DSM-CNRS/IN2P3, BP 55027, F-14076 Caen (France); Ganioğlu, E. [Department of Physics, Istanbul University, Istanbul (Turkey); Gerbaux, M.; Giovinazzo, J.; Grevy, S. [CENBG, Université Bordeaux 1, UMR 5797 CNRS/IN2P3, BP 120, F-33175 Gradignan (France); and others

    2014-06-15

    This paper concerns the experimental study of the β decay properties of few proton-rich fp-shell nuclei. The nuclei were produced at GANIL in fragmentation reactions, separated with the LISE spectrometer and stopped in an implantation detector surrounded by Ge detectors. The β-delayed gammas, β-delayed protons and the exotic β-delayed gamma-proton emission have been studied. Preliminary results are presented. The decay of the T{sub z}=−2 nucleus {sup 56}Zn has been studied in detail. Information from the β-delayed protons and β-delayed gammas has been used to deduce the decay scheme. The exotic beta-delayed gamma-proton decay has been observed for the first time in the fp-shell. The interpretation of the data was made possible thanks to the detailed knowledge of the mirror Charge Exchange (CE) process and the gamma de-excitation of the states in {sup 56}Co, the mirror nucleus of {sup 56}Cu.

  15. An Integrated Data-Driven Strategy for Safe-by-Design Nanoparticles: The FP7 MODERN Project.

    Science.gov (United States)

    Brehm, Martin; Kafka, Alexander; Bamler, Markus; Kühne, Ralph; Schüürmann, Gerrit; Sikk, Lauri; Burk, Jaanus; Burk, Peeter; Tamm, Tarmo; Tämm, Kaido; Pokhrel, Suman; Mädler, Lutz; Kahru, Anne; Aruoja, Villem; Sihtmäe, Mariliis; Scott-Fordsmand, Janeck; Sorensen, Peter B; Escorihuela, Laura; Roca, Carlos P; Fernández, Alberto; Giralt, Francesc; Rallo, Robert

    2017-01-01

    The development and implementation of safe-by-design strategies is key for the safe development of future generations of nanotechnology enabled products. The safety testing of the huge variety of nanomaterials that can be synthetized is unfeasible due to time and cost constraints. Computational modeling facilitates the implementation of alternative testing strategies in a time and cost effective way. The development of predictive nanotoxicology models requires the use of high quality experimental data on the structure, physicochemical properties and bioactivity of nanomaterials. The FP7 Project MODERN has developed and evaluated the main components of a computational framework for the evaluation of the environmental and health impacts of nanoparticles. This chapter describes each of the elements of the framework including aspects related to data generation, management and integration; development of nanodescriptors; establishment of nanostructure-activity relationships; identification of nanoparticle categories; hazard ranking and risk assessment.

  16. The short range effective interaction and the spectra of calcium isotopes in (f-p) space

    International Nuclear Information System (INIS)

    Qing-ying, Z.; Shen-wu, L.; Jian-xin, W.

    1986-01-01

    In this work, the authors use a new type of extremely short range interaction, the double delta interaction (DDI) to calculate the low-lying spectra of calcium isotopes /sup 41/Ca through /sup 48/Ca. The configuration space (f-p) includes configurations ( f/sub 7/2//sup n/ ) and ( f/sub 7/2//sup n-1/2p/sub 3/2/). The calculated energies are compared with experimental data for 75 levels. For comparison, they also use usual modified surface delta interaction (MSDI) to calculate the same spectra aforementioned. It is clear that the results calculated with DDI are better than with MSDI. Therefore, in the short-range effective interaction the addition of body delta force to the modified surface delta force may improve the agreement with experiment. The authors believe that the conclusion will not be changed if one enlarges the shell model space

  17. 2nd FP7 Conference and International Summer School Nanotechnology : From Fundamental Research to Innovations

    CERN Document Server

    Yatsenko, Leonid

    2015-01-01

    This book presents some of the latest achievements in nanotechnology and nanomaterials from leading researchers in Ukraine, Europe, and beyond. It features contributions from participants in the 2nd International Summer School “Nanotechnology: From Fundamental Research to Innovations” and International Research and Practice Conference “Nanotechnology and Nanomaterials”, NANO-2013, which were held in Bukovel, Ukraine on August 25-September 1, 2013. These events took place within the framework of the European Commission FP7 project Nanotwinning, and were organized jointly by the Institute of Physics of the National Academy of Sciences of Ukraine, University of Tartu (Estonia), University of Turin (Italy), and Pierre and Marie Curie University (France). Internationally recognized experts from a wide range of universities and research institutions share their knowledge and key results on topics ranging from nanooptics, nanoplasmonics, and interface studies to energy storage and biomedical applications. Pr...

  18. Recent advances in the management of pulmonary arterial hypertension [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Halley Tsai

    2016-11-01

    Full Text Available Over the past 20 years, there has been an explosion in the development of therapeutics to treat pulmonary arterial hypertension (PAH, a rare but life-threatening disorder associated with progressive elevation of pulmonary pressures and severe right heart failure. Recently, the field has seen the introduction of riociguat, a soluble guanylate cyclase stimulator, a new endothelin receptor antagonist (macitentan, and oral prostanoids (treprostinil and selexipag. Besides new drugs, there have been significant advances in defining the role of upfront combination therapy in treatment-naïve patients as well as proposed methods to deliver systemic prostanoids by use of implantable pumps. In this review, we will touch upon the most important developments in PAH therapeutics over the last three years and how these have changed the guidelines for the treatment of PAH. These exciting developments herald a new era in the treatment of PAH which will be punctuated by the use of more clinically relevant endpoints in clinical research trials and a novel treatment paradigm that may involve upfront double- or triple-combination therapy. We anticipate that the future will make use of these strategies to test the efficacy of upcoming new drugs that aspire to reduce disease progression and improve survival in patients afflicted with this devastating disease.

  19. Improvement of metabolic disorders by an EP2 receptor agonist via restoration of the subcutaneous adipose tissue in pulmonary emphysema.

    Science.gov (United States)

    Tsuji, Takao; Yamaguchi, Kazuhiro; Kikuchi, Ryota; Nakamura, Hiroyuki; Misaka, Ryoichi; Nagai, Atsushi; Aoshiba, Kazutetsu

    2017-05-01

    Chronic obstructive pulmonary disease (COPD) is often associated with co-morbidities. Metabolic disorders like hyperlipidemia and diabetes occur also in underweight COPD patients, although the mechanism is uncertain. Subcutaneous adipose tissue (SAT) plays an important role in energy homeostasis, since restricted capacity to increase fat cell number with increase in fat cell size occurring instead, is associated with lipotoxicity and metabolic disorders. The aim of this study is to show the protective role of SAT for the metabolic disorders in pulmonary emphysema of a murine model. We found ectopic fat accumulation and impaired glucose homeostasis with wasting of SAT in a murine model of elastase-induced pulmonary emphysema (EIE mice) reared on a high-fat diet. ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, improved angiogenesis and subsequently adipogenesis, and finally improved ectopic fat accumulation and glucose homeostasis with restoration of the capacity for storage of surplus energy in SAT. These results suggest that metabolic disorders like hyperlipidemia and diabetes occured in underweight COPD is partially due to the less capacity for storage of surplus energy in SAT, though the precise mechanism is uncertained. Our data pave the way for the development of therapeutic interventions for metabolic disorders in emphysema patients, e.g., use of pro-angiogenic agents targeting the capacity for storage of surplus energy in the subcutaneous adipose tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Extrastriatal binding of [{sup 123}I]FP-CIT in the thalamus and pons: gender and age dependencies assessed in a European multicentre database of healthy controls

    Energy Technology Data Exchange (ETDEWEB)

    Koch, Walter; Unterrainer, Marcus; Xiong, Guoming; Bartenstein, Peter [University of Munich, Department of Nuclear Medicine, Munich (Germany); Diemling, Markus [Hermes Medical Solutions, Stockholm (Sweden); Varrone, Andrea [Karolinska University Hospital, Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm (Sweden); Dickson, John C. [UCLH NHS Foundation Trust and University College, Institute of Nuclear Medicine, London (United Kingdom); Tossici-Bolt, Livia [University Hospitals Southampton NHS Trust, Department of Medical Physics, Southampton (United Kingdom); Sera, Terez [University of Szeged, Department of Nuclear Medicine and Euromedic Szeged, Szeged (Hungary); Asenbaum, Susanne [Medical University of Vienna, Department of Neurology, Vienna (Austria); Booij, Jan [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Centre, Amsterdam (Netherlands); Kapucu, Ozlem L. [Gazi University, Department of Nuclear Medicine, Faculty of Medicine, Ankara (Turkey); Kluge, Andreas [ABX-CRO, Dresden (Germany); Ziebell, Morten [Rigshospitalet and University of Copenhagen, Neurobiology Research Unit, Copenhagen (Denmark); Darcourt, Jacques [University of Nice-Sophia Antipolis, Nuclear Medicine Department, Centre Antoine Lacassagne, Nice (France); Nobili, Flavio [University of Genoa, Clinical Neurology Unit, Department of Neuroscience (DINOGMI), Genoa (Italy); Pagani, Marco [CNR, Institute of Cognitive Sciences and Technologies, Rome (Italy); Karolinska Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Hesse, Swen [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Leipzig University Medical Centre, Molecular Neuroimaging IFB Adiposity Diseases, Leipzig (Germany); Borght, Thierry Vander [Universite Catholique de Louvain, Nuclear Medicine Division, CHU Dinant Godinne, Yvoir (Belgium); Laere, Koen van [University Hospital and K.U. Leuven, Nuclear Medicine, Leuven (Belgium); Tatsch, Klaus [Staedtisches Klinikum Karlsruhe, Department of Nuclear Medicine, Karlsruhe (Germany); La Fougere, Christian [University of Munich, Department of Nuclear Medicine, Munich (Germany); University of Tuebingen, Department of Nuclear Medicine, Tuebingen (Germany)

    2014-10-15

    Apart from binding to the dopamine transporter (DAT), [{sup 123}I]FP-CIT shows moderate affinity for the serotonin transporter (SERT), allowing imaging of both monoamine transporters in a single imaging session in different brain areas. The aim of this study was to systematically evaluate extrastriatal binding (predominantly due to SERT) and its age and gender dependencies in a large cohort of healthy controls. SPECT data from 103 healthy controls with well-defined criteria of normality acquired at 13 different imaging centres were analysed for extrastriatal binding using volumes of interest analysis for the thalamus and the pons. Data were examined for gender and age effects as well as for potential influence of striatal DAT radiotracer binding. Thalamic binding was significantly higher than pons binding. Partial correlations showed an influence of putaminal DAT binding on measured binding in the thalamus but not on the pons. Data showed high interindividual variation in extrastriatal binding. Significant gender effects with 31 % higher binding in women than in men were observed in the thalamus, but not in the pons. An age dependency with a decline per decade (±standard error) of 8.2 ± 1.3 % for the thalamus and 6.8 ± 2.9 % for the pons was shown. The potential to evaluate extrastriatal predominant SERT binding in addition to the striatal DAT in a single imaging session was shown using a large database of [{sup 123}I]FP-CIT scans in healthy controls. For both the thalamus and the pons, an age-related decline in radiotracer binding was observed. Gender effects were demonstrated for binding in the thalamus only. As a potential clinical application, the data could be used as a reference to estimate SERT occupancy in addition to nigrostriatal integrity when using [{sup 123}I]FP-CIT for DAT imaging in patients treated with selective serotonin reuptake inhibitors. (orig.)

  1. The LP-FP-2 severe fuel damage scenario and discussion of the relative influence of the transient and reflood phases in affecting the final condition of the bundle

    International Nuclear Information System (INIS)

    Modro, S.M.; Carboneau, M.L.

    1990-01-01

    The purpose of this paper is to review the evidence from the OECD LP-FP-2 experiment that a high temperature excursion occurred within the center fuel module (CFM) during the reflood portion of the test, was caused by rapid metal-water reaction. It is shown that this reflood scenario explains many perplexing observations from the experiment, in particular, the small amount of fission products and hydrogen transported to the blowdown suppression tank (BST) as compared with the larger quantities trapped within the primary coolant system (PCS). The timing and destruction of the CFM upper tie plate, as well as the transport of fuel debris to the top of this plate, are also explained. In general, all measurements, observations, and analyses of the LP-FP-2 data indicate that most of the CFM damage occurred during a relatively short period of time coincident with the reflood portion of the experiment. 4 refs., 6 figs

  2. Easy handling of tectonic data: the programs TectonicVB for Mac and TectonicsFP for Windows™

    Science.gov (United States)

    Ortner, Hugo; Reiter, Franz; Acs, Peter

    2002-12-01

    TectonicVB for Macintosh and TectonicsFP for Windows TM operating systems are two menu-driven computer programs which allow the shared use of data on these environments. The programs can produce stereographic plots of orientation data (great circles, poles, lineations). Frequently used statistical procedures like calculation of eigenvalues and eigenvectors, calculation of mean vector with concentration parameters and confidence cone can be easily performed. Fault data can be plotted in stereographic projection (Angelier and Hoeppener plots). Sorting of datasets into homogeneous subsets and rotation of tectonic data can be performed in interactive two-diagram windows. The paleostress tensor can be calculated from fault data sets using graphical (calculation of kinematic axes and right dihedra method) or mathematical methods (direct inversion or numerical dynamical analysis). The calculations can be checked in dimensionless Mohr diagrams and fluctuation histograms.

  3. Genetic deletion of the P2Y2 receptor offers significant resistance to development of lithium-induced polyuria accompanied by alterations in PGE2 signaling.

    Science.gov (United States)

    Zhang, Yue; Pop, Ioana L; Carlson, Noel G; Kishore, Bellamkonda K

    2012-01-01

    Lithium (Li)-induced polyuria is due to resistance of the medullary collecting duct (mCD) to the action of arginine vasopressin (AVP), apparently mediated by increased production of PGE(2). We previously reported that the P2Y(2) receptor (P2Y(2)-R) antagonizes the action of AVP on the mCD and may play a role in Li-induced polyuria by enhancing the production of PGE(2) in mCD. Hence, we hypothesized that genetic deletion of P2Y(2)-R should ameliorate Li-induced polyuria. Wild-type (WT) or P2Y(2)-R knockout (KO) mice were fed normal or Li-added diets for 14 days and euthanized. Li-induced polyuria, and decreases in urine osmolality and AQP2 protein abundance in the renal medulla, were significantly less compared with WT mice despite the lack of differences in Li intake or terminal serum or inner medullary tissue Li levels. Li-induced increased urinary excretion of PGE(2) was not affected in KO mice. However, prostanoid EP(3) receptor (EP3-R) protein abundance in the renal medulla of KO mice was markedly lower vs. WT mice, irrespective of the dietary regimen. The protein abundances of other EP-Rs were not altered across the groups irrespective of the dietary regimen. Ex vivo stimulation of mCD with PGE(2) generated significantly more cAMP in Li-fed KO mice (130%) vs. Li-fed WT mice (100%). Taken together, these data suggest 1) genetic deletion of P2Y(2)-R offers significant resistance to the development of Li-induced polyuria; and 2) this resistance is apparently due to altered PGE(2) signaling mediated by a marked decrease in EP3-R protein abundance in the medulla, thus attenuating the EP3-mediated decrease in cAMP levels in mCD.

  4. Implementasi Data Mining Dalam Data Bencana Tanah Longsor Di Jawa Barat Menggunakan Algoritma Fp-Growth

    Directory of Open Access Journals (Sweden)

    Castaka Agus Sugianto

    2017-11-01

    Full Text Available Jawa Barat merupakan salah satu zona rawan longsor di Indonesia. Pengurangan resiko bencana diantaranya adalah peringatan dini dengan langkah awal menganalisis data yang ada. Salah satu cara menganalisis data ini yaitu dengan teknik data mining. Tujuan penelitian ini adalah untuk mengetahui pola hubungan aturan assosiatif antara suatu kombinasi data dan membentuk pola kombinasi datasets dengan menggunakan algoritma Fp-growth dalam data bencana tanah longsor yang di dapat dari Badan Nasional Penanggulangan Bencana dan Badan Penanggulangan Bencana Daerah Provinsi Jawa Barat periode data dari 2011 sampai dengan 2016. Hasil penelitian ini mendapatkan nilai confidence tertinggi sebesar 1 dengan premises malam, jalan rusak dan conclusion hujan deras dan premises tanah labil, korban jiwa, sore dengan conclusion hujan deras yang berarti keterkaitan satu kondisi dengan kondisi lain sebesar 100%. Untuk nilai support tertinggi dalam pola asosiatif didapatkan sebesar 0,629 dengan confidence 0,901 dengan premises rumah rusak dan conclusion hujan deras yang berarti 90% keterkaitan dengan kejadian 63% kemunculan.

  5. Cycloxygenase-2 is expressed in vasculature of normal and ischemic adult human kidney and is colocalized with vascular prostaglandin E2 EP4 receptors

    DEFF Research Database (Denmark)

    Therland, Karina L; Stubbe, Jane; Thiesson, Helle C

    2004-01-01

    The study was performed to elucidate the distribution and cellular localization of cyclooxygenase (COX)-2 in human kidney and to address localization of downstream targets for COX-derived prostanoids. Cortex and outer and inner medulla tissue were obtained from control kidneys (cancer specimens),...... feature encountered in human kidneys at all ages, whereas COX-2 was seen in macula densa only in fetal kidney. Vascular COX-2 activity in human kidney and extrarenal tissues may support blood flow and affect vascular wall-blood interaction....

  6. General and preliminary thermohydraulic, hydrogen and aerosol instrumentation plan for the Phebus Fp-project

    International Nuclear Information System (INIS)

    Hampel, G.; Poss, G.; Frohlich, H.K.

    1989-10-01

    The objective of the project was to draw up an instrumentation plan for the French core melting programme PHEBUS FP. This instrumentation plan essentially was to include proven and reliable instruments for recording various thermohydraulic, aerosol and hydrogen phenomena. The candidate measuring methods, which are known mainly from reactor safety programmes, have been described and examined for their usefulness in PHEBUS. Each method and instrument has been described in detail under various aspects such as measuring principle, measuring range, technical design, evaluation model, calibration procedure, accuracy, previous experience, commercial availability, etc. Special attention has been paid to the behaviour of the measuring transducers when exposed to radiation. First, the performance of the instruments was compared with the requirements of PHEBUS. The results of this comparison served as the basis for a measuring concept in tabular form, giving the locations of the measurements, the measuring tasks, and the number and kind of instruments that are recommended. Redundancy and cost-benefit aspects have been taken into account in qualitative terms

  7. Re-evaluation of thin layer chromatography as an alternative method for the quantification of prostaglandins from rat Kupffer cells.

    Science.gov (United States)

    Pestel, Sabine; Jungermann, Kurt; Schieferdecker, Henrike L

    2005-01-01

    In contrast to conventionally used immunoassays, thin layer chromatography (TLC)--by prelabeling of cells with radioactive arachidonic acid (AA)--allows to differentiate between cellularly built and added prostanoids and thus to investigate feedback effects of prostanoids on their own release. PGD2, TXB2 and PGE2 released from zymosan-stimulated Kupffer cells were separated with distinct RF-values, corresponding to those of the pure substances. Quantification of PGD2 and PGE2 gave comparable results with TLC and immunoassays, but measurement in the presence of added prostanoids was only possible with TLC. Moreover TLC was superior to immunoassays in having a longer linear range while being comparably sensitive. Cellularly built TXB2 in its radioactively labeled form was not detectable by TLC. Inhibition of TXB2 release by externally added AA or technical artifacts were excluded, suggesting that the cellular AA-pools used for prostaglandin and thromboxane synthesis differ in their accessibility for added AA. Thus, TLC is a simple, sensitive and precise method for the quantification of cellularly built prostaglandins but not of thromboxane even in the presence of added prostanoids.

  8. Pathophysiological role of prostaglandin E2-induced up-regulation of the EP2 receptor in motor neuron-like NSC-34 cells and lumbar motor neurons in ALS model mice.

    Science.gov (United States)

    Kosuge, Yasuhiro; Miyagishi, Hiroko; Yoneoka, Yuki; Yoneda, Keiko; Nango, Hiroshi; Ishige, Kumiko; Ito, Yoshihisa

    2017-07-04

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective degeneration of motor neurons. The primary triggers for motor neuronal death are still unknown, but inflammation is considered to be an important factor contributing to the pathophysiology of ALS both clinically and in ALS models. Prostaglandin E2 (PGE2) and its corresponding four E-prostanoid receptors play a pivotal role in the degeneration of motor neurons in human and transgenic models of ALS. It has also been shown that PGE2-EP2 signaling in glial cells (astrocytes or microglia) promotes motor neuronal death in G93A mice. The present study was designed to investigate the levels of expression of EP receptors in the spinal motor neurons of ALS model mice and to examine whether PGE2 alters the expression of EP receptors in differentiated NSC-34 cells, a motor neuron-like cell line. Immunohistochemical staining demonstrated that EP2 and EP3 immunoreactivity was localized in NeuN-positive large cells showing the typical morphology of motor neurons in mice. Semi-quantitative analysis showed that the immunoreactivity of EP2 in motor neurons was significantly increased in the early symptomatic stage in ALS model mice. In contrast, the level of EP3 expression remained constant, irrespective of age. In differentiated NSC-34 cells, bath application of PGE2 resulted in a concentration-dependent decrease of MTT reduction. Although PGE2 had no effect on cell survival at concentrations of less than 10 μM, pretreatment with 10 μM PGE2 significantly up-regulated EP2 and concomitantly potentiated cell death induced by 30 μM PGE2. These results suggest that PGE2 is an important effector for induction of the EP2 subtype in differentiated NSC-34 cells, and that not only EP2 up-regulation in glial cells but also EP2 up-regulation in motor neurons plays a pivotal role in the vulnerability of motor neurons in ALS model mice. Copyright © 2017 Elsevier Ltd. All rights

  9. The discriminating nature of dopamine transporter image in parkinsonism: the competency of dopaminergic transporter imaging in differential diagnosis of parkinsonism {sup 123}I-FP-CIT SPECT study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bom Sahn; Jang, Sung June; Eo, Jae Seon; Park, Eun Kyung; Kim, Yu Kyeong; Kim, Jong Min; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2007-08-15

    The aim of this study was to evaluate the discriminating nature of {sup 123}I-FP-CIT SPECT in patients with parkinsonism. {sup 123}I-FP-CIT SPECT images acquired from the 18 normal controls; NC (60.4 {+-} 10.0 yr) and 237 patients with parkinsonism (65.9 {+-} 9.2 yr) were analyzed. From spatially normalized images, regional counts of the caudate, putamen, and occipital lobe were obtained using region of interest method. Binding potential (BP) was calculated with the ratio of specific to nonspecific binding activity at equilibrium. Additionally, the BP ratio of putamen to caudate (PCR) and asymmetric index (ASI) were measured. BPs of NC (3.37 {+-} 0.57, 3.10{+-} 0.41, 3.23 {+-} 0.48 for caudate, putamen, whole striatum, respectively) had no significant difference with those of essential tremor; ET (3.31 {+-} 0.64, 3.06 {+-} 0.61, 3.14 {+-} 0.63) and Alzheimer's disease; AD (3.33 {+-} 0.60, 3.29 {+-} 0.79, 3.31 {+-} 0.70), but were higher than those of Parkinson's disease; PD (1.92 {+-} 0.74, 1.39 {+-}0.68, 1.64 {+-} 0.68), multiple system atrophy; MSA (2.36 {+-} 1.07, 2.16 {+-} 0.91, 2.26 {+-} 0.96), and dementia with Lewy body; DLB (1.95{+-} 0.72, 1.64 {+-} 0.65, 1.79 {+-} 0.66)({rho} < 0.005). PD had statistically lower values of PCR and higher values of ASI than those of NC ({rho} < 0.005). And PD had significantly lower value of PCR, higher ASI and lower BP in the putamen and whole striatum than MSA ({rho} < 0.05). Dopamine transporter image of {sup 123}I-FP-CIT SPECT was a good value in differential diagnosis of parkinsonism.

  10. FOXC1 Regulates Expression of Prostaglandin Receptors Leading to an Attenuated Response to Latanoprost.

    Science.gov (United States)

    Doucette, Lance P; Footz, Tim; Walter, Michael A

    2018-05-01

    This study examines the effect of FOXC1 on the prostaglandin pathway in order to explore FOXC1's role in the prostaglandin-resistant glaucoma phenotype commonly seen in Axenfeld-Rieger syndrome. Binding and transcriptional activity of FOXC1 to the gene coding for the EP3 prostaglandin receptor (PTGER3) were evaluated through ChIP-qPCR and luciferase-based assays. Immortalized trabecular meshwork cells (TM1) and HeLa cells had FOXC1 mRNA reduced via siRNA interference. qPCR and Western blot experiments were conducted to examine the changes in prostaglandin receptor expression brought about by lowered FOXC1. TM1 cells were then treated with 10 μM latanoprost acid and/or an siRNA for FOXC1. The expression of fibronectin and matrix metalloproteinase 9 were evaluated via qPCR in each treatment condition. ChIP-qPCR and luciferase experiments confirmed that FOXC1 binds to and activates transcription of the EP3 gene prostaglandin receptor. qPCR and Western experiments in HeLa and TM1 cells showed that FOXC1 siRNA knockdown results in significantly lowered EP3 levels (protein and RNA). In addition, RNA levels of the other prostaglandin receptor genes EP1 (PTGER1), EP2 (PTGER2), EP4 (PTGER4), and FP (PTGFR) were altered when FOXC1 was knocked down in TM1 and HeLa cells. Analysis of fibronectin expression in TM1 cells after treatment with 10 μM latanoprost acid showed a statistically significant increase in expression; this increase was abrogated by cotreatment with a siRNA for FOXC1. We show the abrogation of latanoprost signalling when FOXC1 is knocked down via siRNA in a trabecular meshwork cell line. We propose that the lower levels of active FOXC1 in Axenfeld-Rieger syndrome patients with glaucoma account for the lack of response to prostaglandin-based medications.

  11. Evaluation of a second trimester triple marker screening test for fetal status using alpha-fetoprotein (aFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE3)

    International Nuclear Information System (INIS)

    Mi, Seong Young; Kim, Jong Ho; Choi, Seung Hun

    1997-01-01

    Our purpose was to assess the utility of maternal serum triple-marker screening test using alpha-fetoprotein (aFP), human Chorionic Gonadotropin (hCG) and unconjugated Estriol (uE 3 ) for fetal chromosomal abnormalities. 1,767 venous blood samples (4ml) between 15 and 20 week's gestation for maternal serum screening from January to October 1996, were tested with Kodak Amerix-M triple marker radioimmunoassay kits. Risk analysis was achieved with interpretive software such as Alpha (LMS, Kodak Clinical Diagnostics). Marker levels are transformed into multiples of median (MOM), which represent an interpretation of (weight regressed) patient marker levels relative to regressed median levels for stated gestation. By multivariate anaysis, the three MOM values are combined to generate a liklihood ratio. Calculation of a patient, risk is the product of liklihood ratio and age-related risk. Risk assessment is weight for maternal age. The median values of aFP, hCG and uE 3 were well correlated with gestational age, respectively (r=0.94, p=0.003; r=-0.97, p=0.029; r=0.99, p 3 weren't (r=-0.17, p=0.22; r=0.36, p=0.09, respectively). The values of aFP, CG and uE 3 between pregnancy younger than 35 years-old (n=87) and older than that (n=1640) were 51.67±27.44, vs 54.65±126.36, 46.45±30.08 vs 51.33±38.50 and 8.01±11.01 vs 6.68±7.23, respectively but all of them failed to show significant differences. A second-trimester risk for trisomy 21 > or = 1:270 was considered screen positive. Patients were screen positive for trisomy 21 if aFP or 2.1 MOM and E 3 2.5 MOM. The initial screen-positive rate for both Down' syndrome and neural tube defect were 1.46% (26/1767); 0.73% (13/1767) with each other. Among screen positive 26 patients, three and nine were normal karyotype and normal phenotype, respectively and five patients had still births. Reamining 9 patients underwent terminations. In conclusion, compared with the other group's data even in Koreans (Whang et al, and Song et al

  12. Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology.

    Science.gov (United States)

    Fuxe, K; Marcellino, D; Rivera, A; Diaz-Cabiale, Z; Filip, M; Gago, B; Roberts, D C S; Langel, U; Genedani, S; Ferraro, L; de la Calle, A; Narvaez, J; Tanganelli, S; Woods, A; Agnati, L F

    2008-08-01

    Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson's disease, schizophrenia and drug addiction or drug dependence may substantially build on the existence of intramembrane receptor-receptor interactions within dopamine receptor containing receptor mosaics (RM; dimeric or high-order receptor oligomers) where it is believed that the dopamine D(2) receptor may operate as the 'hub receptor' within these complexes. The constitutive adenosine A(2A)/dopamine D(2) RM, located in the dorsal striato-pallidal GABA neurons, are of particular interest in view of the demonstrated antagonistic A(2A)/D(2) interaction within these heteromers; an interaction that led to the suggestion and later demonstration that A(2A) antagonists could be used as novel anti-Parkinsonian drugs. Based on the likely existence of A(2A)/D(2)/mGluR5 RM located both extrasynaptically on striato-pallidal GABA neurons and on cortico-striatal glutamate terminals, multiple receptor-receptor interactions within this RM involving synergism between A(2A)/mGluR5 to counteract D(2) signaling, has led to the proposal of using combined mGluR5 and A(2A) antagonists as a future anti-Parkinsonian treatment. Based on the same RM in the ventral striato-pallidal GABA pathways, novel strategies for the treatment of schizophrenia, building on the idea that A(2A) agonists and/or mGluR5 agonists will help reduce the increased dopaminergic signaling associated with this disease, have been suggested. Such treatment may ensure the proper glutamatergic drive from the mediodorsal thalamic nucleus to the prefrontal cortex, one which is believed to be reduced in schizophrenia due to a dominance of D(2)-like signaling in the ventral striatum. Recently, A(2A) receptors also have been shown to counteract the locomotor and sensitizing actions of cocaine and increases in A(2A) receptors have also been observed in the nucleus accumbens after extended cocaine self-administration, probably

  13. Clinical effects of FP and Addie injection combined with 125I seed implantation in treating advanced primary liver cancer%FP+艾迪注射液联合125I粒子植入治疗中晚期原发性肝癌的临床研究

    Institute of Scientific and Technical Information of China (English)

    张大为; 何津; 吴会静; 张海光; 张青芸; 马一夫; 马龙滨; 陈宝明

    2016-01-01

    Objective To observe the clinical effects of FP (5-fluorouracil and cisplatin) and Addie injection combined with 125I seed implantation in treating advanced primary liver cancer. Methods Ninety-five patients with pri-mary liver cancer who were admitted in People's Hospital of Tangshan City between February 2012 and July 2015 were selected as subjects and were randomized into observation group (n=50) and control group (n=45) by random number ta-ble method. The control group was treated with FP combined with 125I seed implantation. On the basis, the observation group was treated additionally with Addie injection, for 2 courses of treatment. The clinical remission rate, Karnofsky Performance Scale (KPS) scores and peripheral blood white blood cell count before and after treatment, incidence of ad-verse reactions, 1-year and 2-year survival rates were compared between the two groups. Results After treatment, the clinical remission rate in observation group (36.0%) was significantly higher than that in control group of 17.8%, P0.05). After treatment, KPS scores of the two groups were increased to (85.3±5.0) and (79.3±5.2) respectively, while peripheral blood white blood cell count were decreased to (5.0±1.6)×109/L and (3.1 ± 1.3) × 109/L, respectively, with statistically significant difference compared with those before treatment and be-tween the two groups (all P0.05);治疗后,观察组与对照组患者的KPS评分分别升高至(85.3±5.0)分、(79.3±5.2)分,外周血白细胞计数分别减少至(5.0±1.6)×109/L、(3.1±1.3)×109/L,较治疗前均改善明显,且观察组治疗后的KPS评分、外周血白细胞计数均高于对照组,差异均有统计学意义(P<0.05).结论 FP+艾迪注射液联合125I粒子植入治疗中晚期原发性肝癌能明显提高临床缓解率与KPS评分,抑制白细胞减少,生存时间得以延长,值得临床推广应用.

  14. Electronic structure and magnetic properties of Pr-Co intermetallics: ab initio FP-LAPW calculations and correlation with experiments

    Science.gov (United States)

    Bakkari, Karim; Fersi, Riadh; Kebir Hlil, El; Bessais, Lotfi; Thabet Mliki, Najeh

    2018-03-01

    First-principle calculations combining density functional theory and the full-potential linearized augmented plane wave (FP-LAPW) method are performed to investigate the electronic and magnetic structure of Pr2Co7 in its two polymorphic forms, (2:7 H) and (2:7 R), for the first time. This type of calculation was also performed for PrCo5 and PrCo2 intermetallics. We have computed the valence density of states separately for spin-up and spin-down states in order to investigate the electronic band structure. This is governed by the strong contribution of the partial DOS of 3d-Co bands compared to the partial DOS of the 4f-Pr bands. Such a high ferromagnetic state is discussed in terms of the strong spin polarization observed in the total DOS. The magnetic moments carried by the Co and Pr atoms located in several sites for all compounds are computed. These results mainly indicate that cobalt atoms make a dominant contribution to the magnetic moments. The notable difference in the atomic moments of Pr and Co atoms between different structural slabs is explained in terms of the magnetic characteristics of the PrCo2 and PrCo5 compounds and the local chemical environments of the Pr and Co atoms in different structural slabs of Pr2Co7. From spin-polarized calculations we have simulated the 3d and 4f band population to estimate the local magnetic moments. These results are in accordance with the magnetic moments calculated using the FP-LAPW method. In addition, the exchange interactions J ij are calculated and used as input for M(T) simulations. Involving the data obtained from the electronic structure calculations, the appropriate Padé Table is applied to simulate the magnetization M(T) and to estimate the mean-field Curie temperature. We report a fairly good agreement between the ab initio calculation of magnetization and Curie temperature with the experimental data.

  15. Variability in the practice of fertility preservation for patients with cancer.

    Directory of Open Access Journals (Sweden)

    Kasey A Reynolds

    Full Text Available Fertility is important to women and men with cancer. While options for fertility preservation (FP are available, knowledge regarding the medical application of FP is lacking. Therefore we examined FP practices for cancer patients among reproductive endocrinologists (REs. A 36 item survey was sent to board-certified REs. 98% of respondents reported counseling women with cancer about FP options. Oocyte and embryo cryopreservation were universally offered by these providers, but variability was noted in reported management of these cases-particularly for women with breast cancer. 86% of the respondents reported using letrozole during controlled ovarian stimulation (COS in patients with estrogen receptor positive (ER+ breast cancer to minimize patient exposure to estrogen. 49% of respondents who reported using letrozole in COS for patients with ER+ breast cancer reported that they would also use letrozole in COS for women with ER negative breast cancer. Variability was also noted in the management of FP for men with cancer. 83% of participants reported counseling men about sperm banking with 22% recommending against banking for men previously exposed to chemotherapy. Overall, 79% of respondents reported knowledge of American Society for Clinical Oncology FP guidelines-knowledge that was associated with providers offering gonadal tissue cryopreservation (RR 1.82, 95% CI 1.14-2.90. These findings demonstrate that RE management of FP in cancer patients varies. Although some variability may be dictated by local resources, standardization of FP practices and communication with treating oncologists may help ensure consistent recommendations and outcomes for patients seeking FP.

  16. Automatic semi-quantification of [(123)I]FP-CIT SPECT scans in healthy volunteers using BasGan version 2

    DEFF Research Database (Denmark)

    Nobili, Flavio; Naseri, Mehrdad; De Carli, Fabrizio

    2013-01-01

    with partial volume effect correction. Multicentre camera inhomogeneity was taken into account by calibrating values on basal ganglia phantom data. SBR in each caudate nucleus (C) and putamen (P) were the dependent variables in a repeated measures general linear model analysis; age, gender, handedness and body...... Medicine). Brain single photon emission computed tomography (SPECT) was acquired by means of dual-head cameras 3 h after [(123)I]FP-CIT administration. Specific to nondisplaceable binding ratios (SBRs) in the basal ganglia were computed using the 'BasGan' software, allowing automatic value extraction...... mass index (BMI) were the independent variables. RESULTS: SBR values in C and P were significantly associated with age (mean rate decrease with age: 0.0306 per year, or 0.57 % of the general mean; p ...

  17. Getting to FP2020: Harnessing the private sector to increase modern contraceptive access and choice in Ethiopia, Nigeria, and DRC.

    Science.gov (United States)

    Riley, Christina; Garfinkel, Danielle; Thanel, Katherine; Esch, Keith; Workalemahu, Endale; Anyanti, Jennifer; Mpanya, Godéfroid; Binanga, Arsène; Pope, Jen; Longfield, Kim; Bertrand, Jane; Shaw, Bryan

    2018-01-01

    An estimated 214 million women have unmet need for family planning in developing regions. Improved utilization of the private sector is key to achieving universal access to a range of safe and effective modern contraceptive methods stipulated by FP2020 and SDG commitments. Until now, a lack of market data has limited understanding of the private sector's role in increasing contraceptive coverage and choice. In 2015, the FPwatch Project conducted representative outlet surveys in Ethiopia, Nigeria, and DRC using a full census approach in selected administrative areas. Every public and private sector outlet with the potential to sell or distribute modern contraceptives was approached. In outlets with modern contraceptives, product audits and provider interviews assessed contraceptive market composition, availability, and price. Excluding general retailers, 96% of potential outlets in Ethiopia, 55% in Nigeria, and 41% in DRC had modern contraceptive methods available. In Ethiopia, 41% of modern contraceptive stocking outlets were in the private sector compared with approximately 80% in Nigeria and DRC where drug shops were dominant. Ninety-five percent of private sector outlets in Ethiopia had modern contraceptive methods available; 37% had three or more methods. In Nigeria and DRC, only 54% and 42% of private sector outlets stocked modern contraceptives with 5% and 4% stocking three or more methods, respectively. High prices in Nigeria and DRC create barriers to consumer access and choice. There is a missed opportunity to provide modern contraception through the private sector, particularly drug shops. Subsidies and interventions, like social marketing and social franchising, could leverage the private sector's role in increasing access to a range of contraceptives. Achieving global FP2020 commitments depends on the expansion of national contraceptive policies that promote greater partnership and cooperation with the private sector and improvement of decisions around

  18. A robust computational solution for automated quantification of a specific binding ratio based on [123I]FP-CIT SPECT images

    International Nuclear Information System (INIS)

    Oliveira, F. P. M.; Tavares, J. M. R. S.; Borges, Faria D.; Campos, Costa D.

    2014-01-01

    The purpose of the current paper is to present a computational solution to accurately quantify a specific to a non-specific uptake ratio in [ 123 I]fP-CIT single photon emission computed tomography (SPECT) images and simultaneously measure the spatial dimensions of the basal ganglia, also known as basal nuclei. A statistical analysis based on a reference dataset selected by the user is also automatically performed. The quantification of the specific to non-specific uptake ratio here is based on regions of interest defined after the registration of the image under study with a template image. The computational solution was tested on a dataset of 38 [ 123 I]FP-CIT SPECT images: 28 images were from patients with Parkinson’s disease and the remainder from normal patients, and the results of the automated quantification were compared to the ones obtained by three well-known semi-automated quantification methods. The results revealed a high correlation coefficient between the developed automated method and the three semi-automated methods used for comparison (r ≥0.975). The solution also showed good robustness against different positions of the patient, as an almost perfect agreement between the specific to non-specific uptake ratio was found (ICC=1.000). The mean processing time was around 6 seconds per study using a common notebook PC. The solution developed can be useful for clinicians to evaluate [ 123 I]FP-CIT SPECT images due to its accuracy, robustness and speed. Also, the comparison between case studies and the follow-up of patients can be done more accurately and proficiently since the intra- and inter-observer variability of the semi-automated calculation does not exist in automated solutions. The dimensions of the basal ganglia and their automatic comparison with the values of the population selected as reference are also important for professionals in this area.

  19. Probiotic Streptococcus thermophilus FP4 and Bifidobacterium breve BR03 Supplementation Attenuates Performance and Range-of-Motion Decrements Following Muscle Damaging Exercise

    Directory of Open Access Journals (Sweden)

    Ralf Jäger

    2016-10-01

    Full Text Available Probiotics have immunomodulatory effects. However, little is known about the potential benefit of probiotics on the inflammation subsequent to strenuous exercise. In a double-blind, randomized, placebo controlled, crossover design separated by a 21-day washout, 15 healthy resistance-trained men ingested an encapsulated probiotic Streptococcus (S. thermophilus FP4 and Bifidobacterium (B. breve BR03 at 5 bn live cells (AFU concentration each, or a placebo, daily for 3 weeks prior to muscle-damaging exercise (ClinicalTrials.gov NCT02520583. Isometric strength, muscle soreness, range of motion and girth, and blood interleukin-6 (IL-6 and creatine kinase (CK concentrations were measured from pre- to 72 h post-exercise. Statistical analysis was via mixed models and magnitude-based inference to the standardized difference. Probiotic supplementation resulted in an overall decrease in circulating IL-6, which was sustained to 48 h post-exercise. In addition, probiotic supplementation likely enhanced isometric average peak torque production at 24 to 72 h into the recovery period following exercise (probiotic–placebo point effect ±90% CI: 24 h, 11% ± 7%; 48 h, 12% ± 18%; 72 h, 8% ± 8%. Probiotics also likely moderately increased resting arm angle at 24 h (2.4% ± 2.0% and 48 h (1.9% ± 1.9% following exercise, but effects on soreness and flexed arm angle and CK were unclear. These data suggest that dietary supplementation with probiotic strains S. thermophilus FP4 and B. breve BR03 attenuates performance decrements and muscle tension in the days following muscle-damaging exercise.

  20. Probiotic Streptococcus thermophilus FP4 and Bifidobacterium breve BR03 Supplementation Attenuates Performance and Range-of-Motion Decrements Following Muscle Damaging Exercise.

    Science.gov (United States)

    Jäger, Ralf; Purpura, Martin; Stone, Jason D; Turner, Stephanie M; Anzalone, Anthony J; Eimerbrink, Micah J; Pane, Marco; Amoruso, Angela; Rowlands, David S; Oliver, Jonathan M

    2016-10-14

    Probiotics have immunomodulatory effects. However, little is known about the potential benefit of probiotics on the inflammation subsequent to strenuous exercise. In a double-blind, randomized, placebo controlled, crossover design separated by a 21-day washout, 15 healthy resistance-trained men ingested an encapsulated probiotic Streptococcus ( S. ) thermophilus FP4 and Bifidobacterium ( B. ) breve BR03 at 5 bn live cells (AFU) concentration each, or a placebo, daily for 3 weeks prior to muscle-damaging exercise (ClinicalTrials.gov NCT02520583). Isometric strength, muscle soreness, range of motion and girth, and blood interleukin-6 (IL-6) and creatine kinase (CK) concentrations were measured from pre- to 72 h post-exercise. Statistical analysis was via mixed models and magnitude-based inference to the standardized difference. Probiotic supplementation resulted in an overall decrease in circulating IL-6, which was sustained to 48 h post-exercise. In addition, probiotic supplementation likely enhanced isometric average peak torque production at 24 to 72 h into the recovery period following exercise (probiotic-placebo point effect ±90% CI: 24 h, 11% ± 7%; 48 h, 12% ± 18%; 72 h, 8% ± 8%). Probiotics also likely moderately increased resting arm angle at 24 h (2.4% ± 2.0%) and 48 h (1.9% ± 1.9%) following exercise, but effects on soreness and flexed arm angle and CK were unclear. These data suggest that dietary supplementation with probiotic strains S. thermophilus FP4 and B. breve BR03 attenuates performance decrements and muscle tension in the days following muscle-damaging exercise.

  1. Possible Relevance of Receptor-Receptor Interactions between Viral- and Host-Coded Receptors for Viral-Induced Disease

    Directory of Open Access Journals (Sweden)

    Luigi F. Agnati

    2007-01-01

    Full Text Available It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers, but clusters of receptors (receptor mosaics, altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.

  2. Trojan Horse measurement of the {sup 18}F(p, α){sup 15}O astrophysical S(E)-factor

    Energy Technology Data Exchange (ETDEWEB)

    Pizzone, R.G. [Texas A and M University, Cyclotron Institute, College Station, TX (United States); INFN, Laboratori Nazionali del Sud, Catania (Italy); Roeder, B.T.; McCleskey, M. [Texas A and M University, Cyclotron Institute, College Station, TX (United States); Trache, L. [Texas A and M University, Cyclotron Institute, College Station, TX (United States); IFIN-HH, Bucharest-Magurele (Romania); Tribble, R.E. [Texas A and M University, Cyclotron Institute, College Station, TX (United States); Brookhaven National Laboratory, Upton, New York (United States); Spitaleri, C.; Indelicato, I.; Rapisarda, G.G.; Sparta, R. [INFN, Laboratori Nazionali del Sud, Catania (Italy); Universita degli Studi di Catania, Dipartimento di Fisica e Astronomia, Catania (Italy); Bertulani, C.A. [Texas A and M University-Commerce, Department of Physics and Astronomy, Commerce (United States); Cherubini, S. [INFN, Laboratori Nazionali del Sud, Catania (Italy); Brookhaven National Laboratory, Upton, New York (United States); Gulino, M. [INFN, Laboratori Nazionali del Sud, Catania (Italy); KORE University, Enna (Italy); La Cognata, M. [INFN, Laboratori Nazionali del Sud, Catania (Italy); Lamia, L. [Universita degli Studi di Catania, Dipartimento di Fisica e Astronomia, Catania (Italy)

    2016-02-15

    Crucial information on novae nucleosynthesis is linked to the abundance of {sup 18}F, which, due to great improvements in gamma-ray astronomy, can be detected in explosive environments. Therefore, the reaction network producing and destroying this radioactive isotope has been extensively studied in the last years. Among those reactions, the {sup 18}F(p, α){sup 15}O cross section has been measured by means of several dedicated experiments, both using direct and indirect methods. The presence of resonances in the energy region of astrophysical interest has been reported by many authors. In the present work a report on a recent experiment performed via the Trojan Horse Method (THM) is presented and the results are given and compared with the ones known in the literature, both direct and indirect. Data arising from THM measurements are then averaged and the reaction rate calculated in the novae energy range. (orig.)

  3. Ecotoxicity testing and environmental risk assessment of iron nanomaterials for sub-surface remediation – Recommendations from the FP7 project NanoRem

    DEFF Research Database (Denmark)

    Hjorth, Rune; Coutris, Claire; Nguyen, Nhung

    2017-01-01

    engineered Fe nanomaterials, specifically, Nano-Goethite, Trap-Ox Fe-zeolites, Carbo-Iron® and FerMEG12, developed within the European FP7 project NanoRem for sub-surface remediation towards a test battery consisting of eight ecotoxicity tests on bacteria (V. fisheri, E. coli), algae (P. subcapitata...... milled nZVI (FerMEG12), showed no toxicity in the test battery when tested in concentrations up to 100 mg/L, which is the cutoff for hazard labeling in chemicals regulation in Europe. However it should be noted that Fe nanomaterials proved challenging to test adequately due to their turbidity...

  4. Optimization of the reconstruction parameters in [123I]FP-CIT SPECT

    Science.gov (United States)

    Niñerola-Baizán, Aida; Gallego, Judith; Cot, Albert; Aguiar, Pablo; Lomeña, Francisco; Pavía, Javier; Ros, Domènec

    2018-04-01

    The aim of this work was to obtain a set of parameters to be applied in [123I]FP-CIT SPECT reconstruction in order to minimize the error between standardized and true values of the specific uptake ratio (SUR) in dopaminergic neurotransmission SPECT studies. To this end, Monte Carlo simulation was used to generate a database of 1380 projection data-sets from 23 subjects, including normal cases and a variety of pathologies. Studies were reconstructed using filtered back projection (FBP) with attenuation correction and ordered subset expectation maximization (OSEM) with correction for different degradations (attenuation, scatter and PSF). Reconstruction parameters to be optimized were the cut-off frequency of a 2D Butterworth pre-filter in FBP, and the number of iterations and the full width at Half maximum of a 3D Gaussian post-filter in OSEM. Reconstructed images were quantified using regions of interest (ROIs) derived from Magnetic Resonance scans and from the Automated Anatomical Labeling map. Results were standardized by applying a simple linear regression line obtained from the entire patient dataset. Our findings show that we can obtain a set of optimal parameters for each reconstruction strategy. The accuracy of the standardized SUR increases when the reconstruction method includes more corrections. The use of generic ROIs instead of subject-specific ROIs adds significant inaccuracies. Thus, after reconstruction with OSEM and correction for all degradations, subject-specific ROIs led to errors between standardized and true SUR values in the range [‑0.5, +0.5] in 87% and 92% of the cases for caudate and putamen, respectively. These percentages dropped to 75% and 88% when the generic ROIs were used.

  5. Effect of Animal Condition and Fluvoxamine on the Result of [18F]N 3 Fluoropropyl-2β carbomethoxy-3β (4-iodophenyl) Nortropane ([18F]FP-CIT) PET Study in Mice

    International Nuclear Information System (INIS)

    Shin, Kwang Ho; Lee Sang Ju; Oh, Seung Jun; Kim, Jae Seung; Park, Su A; Kim, Seog Young

    2012-01-01

    PET (positron emission tomography) is a noninvasive imaging technique, visualizing biological aspects in vivo. In animal models, the result of PET study can be affected more prominently than in humans by the animal conditions or drug pretreatment. We assessed the effects of anesthesia, body temperature, and pretreatment with selective serotonin reuptake inhibitor on the results of [ 18F ]N 3 fluoropropyl 2β carbomethoxy 3β (4-iodophenyl) nortropane ([ 18F ]FP CIT) PET in mice. [ 18F ]FP CIT PET of C57BL/6 mice was performed in three different conditions: (1) anesthesia (isoflurane) with active warming (38.deg.C) as a reference; (2) no anesthesia or warming; (3) anesthesia without warming at room temperature. Additional groups of mine pretreated with escalating doses of fluvoxamine (5, 20, 40, 80 mg/kg) were imaged in condition (1). The time activity curve and standardized uptake value of the striatum, cerebral cortex, and bone were compared among these conditions. In all conditions, radioactivities of the striatum and cortex tended to form a plateau after rapid uptake and washout, but that of bone tended to increase gradually. When anesthetized without any warming, all the mice developed hypothermia and showed reduced bone uptake compared to the reference condition. In conditions without anesthesia, striatal and cortical uptakes compared to the reference condition. In conditions without anesthesia, striatal and cortical uptakes were reduced, whereas the bone uptake showed no change. Pretreatment with fluvoxamine increased the striatal uptake and striatal specific to cortical non specific uptake ratio, whereas the bone uptake was reduced. Anesthesia, body temperature, and fluvoxamine affect the result of [ 18F ]FP CIT PET in mice by altering striatal and bone uptakes

  6. Fluticasone-formoterol: a systematic review of its potential role in the treatment of asthma

    Directory of Open Access Journals (Sweden)

    Prosser TR

    2015-06-01

    Full Text Available Theresa R Prosser, Suzanne G Bollmeier St Louis College of Pharmacy, St Louis, MO, USA Background: The purpose of this systematic review is to summarize and evaluate the available published data regarding the efficacy and safety of a combination product containing fluticasone propionate/formoterol (FP-F in order to establish its potential role compared with other inhaled combination corticosteroid/long-acting beta2 receptor agonists for the maintenance treatment of asthma.Methods: A PubMed and EMBASE search was conducted using the terms “fluticasone propionate”, “formoterol fumarate”, “Flutiform®”, and “asthma” in July 2014 to identify trials using this combination specifically for the treatment of asthma. Additional information was gathered from references cited in the identified publications, the package insert, and the ClinicalTrials.gov registry. All randomized controlled clinical trials for humans in asthma were evaluated for inclusion. Data from animal trials, clinical trials for chronic obstructive pulmonary disease, and non-English sources were excluded.Results: Seven short-term safety and efficacy trials of FP-F compared with its individual components and two comparison trials of FP-F versus other combination products were identified. Generally, the incidence of drug-related adverse events was low and consistent with previously reported drug class-related adverse events (ie, pharyngitis, dysphonia, and headache. The combination of FP-F was shown to be noninferior to fluticasone propionate/salmeterol for improving predose forced expiratory volume at one second (FEV1 and 2 hours post dose FEV1. FP-F was also noninferior to budesonide/formoterol in improving predose FEV1. Other clinical endpoints, including various symptom scores, asthma control, quality of life, and subjects’ assessment of the medications were not significantly different.Conclusion: Poor asthma control is common. The data from short-term studies

  7. Vehicular Traffic-Related Polycyclic Aromatic Hydrocarbon Exposure and Breast Cancer Incidence: The Long Island Breast Cancer Study Project (LIBCSP)

    Czech Academy of Sciences Publication Activity Database

    Mordukhovich, I.; Beyea, J.; Herring, A. H.; Hatch, M.; Stellman, S. D.; Teitelbaum, S. L.; Richardson, D.B.; Millikan, R. C.; Engel, L.S.; Shantakumar, S.; Steck, S.E.; Neugut, A. I.; Rössner ml., Pavel; Santella, R. M.; Gammon, M. D.

    2016-01-01

    Roč. 124, č. 1 (2016), s. 30-38 ISSN 0091-6765 Institutional support: RVO:68378041 Keywords : hormone-receptor status * time-activity patterns * risk-factors Subject RIV: FP - Other Medical Disciplines Impact factor: 9.776, year: 2016

  8. NLRP3 inflammasome inhibition is disrupted in a group of auto-inflammatory disease CAPS mutations.

    Science.gov (United States)

    Mortimer, Leanne; Moreau, France; MacDonald, Justin A; Chadee, Kris

    2016-10-01

    Inflammasomes are positioned to rapidly escalate the intensity of inflammation by activating interleukin (IL)-1β, IL-18 and cell death by pyroptosis. However, negative regulation of inflammasomes remains poorly understood, as is the signaling cascade that dampens inflammasome activity. We found that rapid NLRP3 inflammasome activation was directly inhibited by protein kinase A (PKA), which was induced by prostaglandin E2 (PGE2) signaling via the PGE2 receptor E-prostanoid 4 (EP4). PKA directly phosphorylated the cytoplasmic receptor NLRP3 and attenuated its ATPase function. We found that Ser295 in human NLRP3 was critical for rapid inhibition and PKA phosphorylation. Mutations in NLRP3-encoding residues adjacent to Ser295 have been linked to the inflammatory disease CAPS (cryopyrin-associated periodic syndromes). NLRP3-S295A phenocopied the human CAPS mutants. These data suggest that negative regulation at Ser295 is critical for restraining the NLRP3 inflammasome and identify a molecular basis for CAPS-associated NLRP3 mutations.

  9. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    functional units, receptors co-operate. The total receptor apparatus of individual cell types is composed of different-ligand receptors (e.g. SRIF and non-SRIF receptors) and co-expressed receptor subtypes (e.g. sst(2) and sst(5) receptors) in characteristic proportions. In other words, levels of individual......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  10. Analysis of reactor-neutrino spectra fully based on gross theory of beta-decay emphasizing the special role of odd-odd FP nuclides

    Science.gov (United States)

    Yoshida, Tadashi; Tachibana, Takahiro; Chiba, Satoshi

    2017-09-01

    We applied the gross theory of β-decay to calculate the reactor antineutrino (νe) spectra emitted from 235,238U and 239,241Pu samples under neutron irradiation by summing up all the contributions from a large number of decaying fission-products (FPs). Considering the special role of the odd(Z)-odd(N) FPs in spectrum-shaping, we utilized the experimentally-known spin-parity of each odd-odd FP through the treatment proposed by Nakata, Tachibana and Yamada. Owing to this treatment, the consistency between calculated and experimental spectra was remarkably improved in a way expected from the nature of the gross theory of β-decay.

  11. Marine prostanoids - a review

    Digital Repository Service at National Institute of Oceanography (India)

    Wahidullah, S.; De

    The occurrence and structure of prostaglandins including clavulones, punaglandins and claviridenones in marine organisms is reviewEd. by comparison of the spectral data reported the identity of 20-acetoxy claviridenones b and c with 20 acetoxy...

  12. Insulin receptors

    International Nuclear Information System (INIS)

    Kahn, C.R.; Harrison, L.C.

    1988-01-01

    This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

  13. Getting to FP2020: Harnessing the private sector to increase modern contraceptive access and choice in Ethiopia, Nigeria, and DRC.

    Directory of Open Access Journals (Sweden)

    Christina Riley

    Full Text Available An estimated 214 million women have unmet need for family planning in developing regions. Improved utilization of the private sector is key to achieving universal access to a range of safe and effective modern contraceptive methods stipulated by FP2020 and SDG commitments. Until now, a lack of market data has limited understanding of the private sector's role in increasing contraceptive coverage and choice.In 2015, the FPwatch Project conducted representative outlet surveys in Ethiopia, Nigeria, and DRC using a full census approach in selected administrative areas. Every public and private sector outlet with the potential to sell or distribute modern contraceptives was approached. In outlets with modern contraceptives, product audits and provider interviews assessed contraceptive market composition, availability, and price.Excluding general retailers, 96% of potential outlets in Ethiopia, 55% in Nigeria, and 41% in DRC had modern contraceptive methods available. In Ethiopia, 41% of modern contraceptive stocking outlets were in the private sector compared with approximately 80% in Nigeria and DRC where drug shops were dominant. Ninety-five percent of private sector outlets in Ethiopia had modern contraceptive methods available; 37% had three or more methods. In Nigeria and DRC, only 54% and 42% of private sector outlets stocked modern contraceptives with 5% and 4% stocking three or more methods, respectively. High prices in Nigeria and DRC create barriers to consumer access and choice.There is a missed opportunity to provide modern contraception through the private sector, particularly drug shops. Subsidies and interventions, like social marketing and social franchising, could leverage the private sector's role in increasing access to a range of contraceptives. Achieving global FP2020 commitments depends on the expansion of national contraceptive policies that promote greater partnership and cooperation with the private sector and improvement of

  14. Getting to FP2020: Harnessing the private sector to increase modern contraceptive access and choice in Ethiopia, Nigeria, and DRC

    Science.gov (United States)

    Garfinkel, Danielle; Thanel, Katherine; Esch, Keith; Workalemahu, Endale; Anyanti, Jennifer; Mpanya, Godéfroid; Binanga, Arsène; Pope, Jen; Longfield, Kim; Bertrand, Jane; Shaw, Bryan

    2018-01-01

    Background An estimated 214 million women have unmet need for family planning in developing regions. Improved utilization of the private sector is key to achieving universal access to a range of safe and effective modern contraceptive methods stipulated by FP2020 and SDG commitments. Until now, a lack of market data has limited understanding of the private sector’s role in increasing contraceptive coverage and choice. Methods In 2015, the FPwatch Project conducted representative outlet surveys in Ethiopia, Nigeria, and DRC using a full census approach in selected administrative areas. Every public and private sector outlet with the potential to sell or distribute modern contraceptives was approached. In outlets with modern contraceptives, product audits and provider interviews assessed contraceptive market composition, availability, and price. Findings Excluding general retailers, 96% of potential outlets in Ethiopia, 55% in Nigeria, and 41% in DRC had modern contraceptive methods available. In Ethiopia, 41% of modern contraceptive stocking outlets were in the private sector compared with approximately 80% in Nigeria and DRC where drug shops were dominant. Ninety-five percent of private sector outlets in Ethiopia had modern contraceptive methods available; 37% had three or more methods. In Nigeria and DRC, only 54% and 42% of private sector outlets stocked modern contraceptives with 5% and 4% stocking three or more methods, respectively. High prices in Nigeria and DRC create barriers to consumer access and choice. Discussion There is a missed opportunity to provide modern contraception through the private sector, particularly drug shops. Subsidies and interventions, like social marketing and social franchising, could leverage the private sector’s role in increasing access to a range of contraceptives. Achieving global FP2020 commitments depends on the expansion of national contraceptive policies that promote greater partnership and cooperation with the private

  15. 99mTc-EDDA/HYNIC-TOC in management of patients with head and neck somatostatin receptor positive tumors.

    Science.gov (United States)

    Trogrlic, Mate; Tezak, Stanko

    2016-01-01

    Aim of this study was to determine the value of technetium-99m-hydrazinonicotinyl-Tyr3-octreotide (99mTc-ED-DA/HYNIC-TOC) in patients with somatostatin receptor (SSR) positive tumors of head and neck region. A total number of 16 patients were enrolled in this study. Planar whole body (WB) and single photon emission computed tomography (SPECT) images were acquired at 2 and 4 hours after the injection of approximately 670 MBq of 99mTc-EDDA/HYNIC-TOC. Additional single photon emission computed tomography/computed tomography (SPECT/CT) images of the head and neck region were acquired at 4h post tracer injection. Clinical and imaging follow up were taken as the reference standard. There were 10 female and 6 male patients of age 57.7 ± 12.9 years (58.5; 32-78) years. 99mTc-EDDA/HYNIC-TOC somatostatin receptor scintigraphy (SRS) was TP in 13 patients, TN in two and FP in one. Follow up period for SRS was 31.1 ± 19.4 (29; 2-63) months. 99mTc-EDDA/HYNIC-TOC scintigraphy provided additional information in 50% of patients, with impact on patient management in the same percentage of patients. Distant metastases were found in nine out of 16 patients (56%). 99mTc-EDDA/HYNIC-TOC SRS had sensitivity of 100% (75.3-100%), specificity of 66.7% (9.4-99.2%), accuracy of 93.7%, positive predictive value of 92.9% (66.1-99.8%), and negative predictive value of 100% (15.8-100%). Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC is very useful imaging method in the evalu-ation of patients with SSR positive tumors of head and neck region.

  16. Apocynin prevents vascular effects caused by chronic exposure to low concentrations of mercury.

    Directory of Open Access Journals (Sweden)

    Danize A Rizzetti

    Full Text Available UNLABELLED: Mercury increases the risk of cardiovascular disease and oxidative stress and alters vascular reactivity. This metal elicits endothelial dysfunction causing decreased NO bioavailability via increased oxidative stress and contractile prostanoid production. NADPH oxidase is the major source of reactive oxygen species (ROS in the vasculature. Our aim was to investigate whether treatment with apocynin, an NADPH oxidase inhibitor, prevents the vascular effects caused by chronic intoxication with low concentrations of mercury. Three-month-old male Wistar rats were treated for 30 days with a intramuscular injections (i.m. of saline; b HgCl(2 (i.m. 1(st dose: 4.6 µg/kg, subsequent doses: 0.07 µg/kg/day; c Apocynin (1.5 mM in drinking water plus saline i.m.; and d Apocynin plus HgCl(2. The mercury treatment resulted in 1 an increased aortic vasoconstrictor response to phenylephrine and reduced endothelium-dependent responses to acetylcholine; 2 the increased involvement of ROS and vasoconstrictor prostanoids in response to phenylephrine, whereas the endothelial NO modulation of such responses was reduced; and 3 the reduced activity of aortic superoxide dismutase (SOD and glutathione peroxidase (GPx and increased plasma malondialdehyde (MDA levels. Treatment with apocynin partially prevented the increased phenylephrine responses and reduced the endothelial dysfunction elicited by mercury treatment. In addition, apocynin treatment increased the NO modulation of vasoconstrictor responses and aortic SOD activity and reduced plasma MDA levels without affecting the increased participation of vasoconstrictor prostanoids observed in aortic segments from mercury-treated rats. CONCLUSIONS: Mercury increases the vasoconstrictor response to phenylephrine by reducing NO bioavailability and increasing the involvement of ROS and constrictor prostanoids. Apocynin protects the vessel from the deleterious effects caused by NADPH oxidase, but not from those

  17. Cyclooxygenases 1 and 2 differentially regulate blood pressure and cerebrovascular responses to acute and chronic intermittent hypoxia: implications for sleep apnea.

    Science.gov (United States)

    Beaudin, Andrew E; Pun, Matiram; Yang, Christina; Nicholl, David D M; Steinback, Craig D; Slater, Donna M; Wynne-Edwards, Katherine E; Hanly, Patrick J; Ahmed, Sofia B; Poulin, Marc J

    2014-05-09

    Obstructive sleep apnea (OSA) is associated with increased risk of cardiovascular and cerebrovascular disease resulting from intermittent hypoxia (IH)-induced inflammation. Cyclooxygenase (COX)-formed prostanoids mediate the inflammatory response, and regulate blood pressure and cerebral blood flow (CBF), but their role in blood pressure and CBF responses to IH is unknown. Therefore, this study's objective was to determine the role of prostanoids in cardiovascular and cerebrovascular responses to IH. Twelve healthy, male participants underwent three, 6-hour IH exposures. For 4 days before each IH exposure, participants ingested a placebo, indomethacin (nonselective COX inhibitor), or Celebrex(®) (selective COX-2 inhibitor) in a double-blind, randomized, crossover study design. Pre- and post-IH blood pressure, CBF, and urinary prostanoids were assessed. Additionally, blood pressure and urinary prostanoids were assessed in newly diagnosed, untreated OSA patients (n=33). Nonselective COX inhibition increased pre-IH blood pressure (P ≤ 0.04) and decreased pre-IH CBF (P=0.04) while neither physiological variable was affected by COX-2 inhibition (P ≥ 0.90). Post-IH, MAP was elevated (P ≤ 0.05) and CBF was unchanged with placebo and nonselective COX inhibition. Selective COX-2 inhibition abrogated the IH-induced MAP increase (P=0.19), but resulted in lower post-IH CBF (P=0.01). Prostanoids were unaffected by IH, except prostaglandin E2 was elevated with the placebo (P=0.02). Finally, OSA patients had elevated blood pressure (P ≤ 0.4) and COX-1 formed thromboxane A2 concentrations (P=0.02). COX-2 and COX-1 have divergent roles in modulating vascular responses to acute and chronic IH. Moreover, COX-1 inhibition may mitigate cardiovascular and cerebrovascular morbidity in OSA. www.clinicaltrials.gov. Unique identifier: NCT01280006.

  18. Enhanced neutralization potency of botulinum neurotoxin antibodies using a red blood cell-targeting fusion protein.

    Directory of Open Access Journals (Sweden)

    Sharad P Adekar

    2011-03-01

    Full Text Available Botulinum neurotoxin (BoNT potently inhibits cholinergic signaling at the neuromuscular junction. The ideal countermeasures for BoNT exposure are monoclonal antibodies or BoNT antisera, which form BoNT-containing immune complexes that are rapidly cleared from the general circulation. Clearance of opsonized toxins may involve complement receptor-mediated immunoadherence to red blood cells (RBC in primates or to platelets in rodents. Methods of enhancing immunoadherence of BoNT-specific antibodies may increase their potency in vivo. We designed a novel fusion protein (FP to link biotinylated molecules to glycophorin A (GPA on the RBC surface. The FP consists of an scFv specific for murine GPA fused to streptavidin. FP:mAb:BoNT complexes bound specifically to the RBC surface in vitro. In a mouse model of BoNT neutralization, the FP increased the potency of single and double antibody combinations in BoNT neutralization. A combination of two antibodies with the FP gave complete neutralization of 5,000 LD50 BoNT in mice. Neutralization in vivo was dependent on biotinylation of both antibodies and correlated with a reduction of plasma BoNT levels. In a post-exposure model of intoxication, FP:mAb complexes gave complete protection from a lethal BoNT/A1 dose when administered within 2 hours of toxin exposure. In a pre-exposure prophylaxis model, mice were fully protected for 72 hours following administration of the FP:mAb complex. These results demonstrate that RBC-targeted immunoadherence through the FP is a potent enhancer of BoNT neutralization by antibodies in vivo.

  19. APhoRISM FP7 project: the Multi-platform volcanic Ash Cloud Estimation (MACE) infrastructure

    Science.gov (United States)

    Merucci, Luca; Corradini, Stefano; Bignami, Christian; Stramondo, Salvatore

    2014-05-01

    APHORISM is an FP7 project that aims to develop innovative products to support the management and mitigation of the volcanic and the seismic crisis. Satellite and ground measurements will be managed in a novel manner to provide new and improved products in terms of accuracy and quality of information. The Multi-platform volcanic Ash Cloud Estimation (MACE) infrastructure will exploit the complementarity between geostationary, and polar satellite sensors and ground measurements to improve the ash detection and retrieval and to fully characterize the volcanic ash clouds from source to the atmosphere. The basic idea behind the proposed method consists to manage in a novel manner, the volcanic ash retrievals at the space-time scale of typical geostationary observations using both the polar satellite estimations and in-situ measurements. The typical ash thermal infrared (TIR) retrieval will be integrated by using a wider spectral range from visible (VIS) to microwave (MW) and the ash detection will be extended also in case of cloudy atmosphere or steam plumes. All the MACE ash products will be tested on three recent eruptions representative of different eruption styles in different clear or cloudy atmospheric conditions: Eyjafjallajokull (Iceland) 2010, Grimsvotn (Iceland) 2011 and Etna (Italy) 2011-2012. The MACE infrastructure will be suitable to be implemented in the next generation of ESA Sentinels satellite missions.

  20. Effect of Animal Condition and Fluvoxamine on the Result of [{sup 18F}]N 3 Fluoropropyl-2{beta} carbomethoxy-3{beta} (4-iodophenyl) Nortropane ([{sup 18F}]FP-CIT) PET Study in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Kwang Ho; Lee Sang Ju; Oh, Seung Jun; Kim, Jae Seung [Asan Medical Center, Univ. of Ulsan College of Medicine, Seoul (Korea, Republic of); Park, Su A [Ulsan National Institute of Science and Technology, Ulsan (Korea, Republic of); Kim, Seog Young [Univ. of Pittsburgh, Pittaburg (United States)

    2012-03-15

    PET (positron emission tomography) is a noninvasive imaging technique, visualizing biological aspects in vivo. In animal models, the result of PET study can be affected more prominently than in humans by the animal conditions or drug pretreatment. We assessed the effects of anesthesia, body temperature, and pretreatment with selective serotonin reuptake inhibitor on the results of [{sup 18F}]N 3 fluoropropyl 2{beta} carbomethoxy 3{beta} (4-iodophenyl) nortropane ([{sup 18F}]FP CIT) PET in mice. [{sup 18F}]FP CIT PET of C57BL/6 mice was performed in three different conditions: (1) anesthesia (isoflurane) with active warming (38.deg.C) as a reference; (2) no anesthesia or warming; (3) anesthesia without warming at room temperature. Additional groups of mine pretreated with escalating doses of fluvoxamine (5, 20, 40, 80 mg/kg) were imaged in condition (1). The time activity curve and standardized uptake value of the striatum, cerebral cortex, and bone were compared among these conditions. In all conditions, radioactivities of the striatum and cortex tended to form a plateau after rapid uptake and washout, but that of bone tended to increase gradually. When anesthetized without any warming, all the mice developed hypothermia and showed reduced bone uptake compared to the reference condition. In conditions without anesthesia, striatal and cortical uptakes compared to the reference condition. In conditions without anesthesia, striatal and cortical uptakes were reduced, whereas the bone uptake showed no change. Pretreatment with fluvoxamine increased the striatal uptake and striatal specific to cortical non specific uptake ratio, whereas the bone uptake was reduced. Anesthesia, body temperature, and fluvoxamine affect the result of [{sup 18F}]FP CIT PET in mice by altering striatal and bone uptakes.

  1. The interleukin-4 receptor: signal transduction by a hematopoietin receptor.

    Science.gov (United States)

    Keegan, A D; Pierce, J H

    1994-02-01

    Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.

  2. Analysis of FP aerosol behavior in piping in WIND project. Contract research

    Energy Technology Data Exchange (ETDEWEB)

    Hidaka, Akihide; Maruyama, Yu; Shibazaki, Hiroaki; Maeda, Akio; Harada, Yuhei [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Nagashima, Toshio; Yoshino, Takehito; Sugimoto, Jun

    1998-07-01

    In the analyses of aerosol behavior test in piping in WIND (Wide Range Piping Integrity Demonstration) project at Japan Atomic Energy Research Institute (JAERI), ART code developed by JAERI and VICTORIA code developed by Sandia National Laboratories are used to perform WIND test analysis and to validate the models in the both codes. It is noted that VICTORIA code is supposed to be used as reference code of ART at JAERI. As a part of these activities, WIND Aerosol Deposition tests (WAD4 and 5) and FP aerosol behaviors in safety relief valve (SRV) line during BWR high pressure sequence which will be performed in future WIND experiment were analyzed with ART and VICTORIA codes. The present analyses showed that the portion and mass with relatively large amount of cesium iodide (CsI) deposition observed in WAD4 and 5 tests were reasonably reproduced by ART and VICTORIA codes. A difference was found in condensation and revaporization behaviors of gaseous CsI between the two codes. VICTORIA overestimated the condensed mass of CsI vapor while ART reproduced better the experimental data than the VICTORIA calculation. Further investigation is needed for this issue. Although the deposition mass at the pipe connection part in WAD4 and 5 experiments was not measured, the mass at that portion will be measured from next experiment because relatively large amount of CsI could be deposited there and the measurement is considered to be useful for code verification. The predicted principal aerosol deposition mechanism in SRV line is turbulence. Temperature of SRV line could increase by about 300 K by decay heat from deposited FPs. However, the SRV line made of carbon steel would not be failed because the predicted temperature is still far lower than the melting temperature of carbon steel. (author)

  3. The LDL receptor.

    Science.gov (United States)

    Goldstein, Joseph L; Brown, Michael S

    2009-04-01

    In this article, the history of the LDL receptor is recounted by its codiscoverers. Their early work on the LDL receptor explained a genetic cause of heart attacks and led to new ways of thinking about cholesterol metabolism. The LDL receptor discovery also introduced three general concepts to cell biology: receptor-mediated endocytosis, receptor recycling, and feedback regulation of receptors. The latter concept provides the mechanism by which statins selectively lower plasma LDL, reducing heart attacks and prolonging life.

  4. Preliminary results of the PREFER FP7 Project

    Science.gov (United States)

    Fusilli, Lorenzo; Laneve, Giovanni; De Bonis, Roberto; Sebastian, Ana; Ferrucci, Fabrizio; Oliveira, Sandra

    2014-05-01

    The need to improve the information and intelligence support for forest fire prevention is widely recognized. Fire prevention is still the most cost-effective strategy when compared to firefighting and extinguishing that are costly, local, and triggered only in response to already ongoing crises. PREFER project, funded under the EU FP7 (G.A. 312931), intends to contribute at responding to such a pragmatic need of southern Europe's forests by: providing timely information products based on the exploitation of all available spacecraft sensors, offering a portfolio of products focused on pre- and post-crisis forest fire emergency, suitable for the users in the different countries of the European Mediterranean area. The PREFER Service portfolio consists of two main services: 1. Information Support to Fire Preparedness/Prevention Phase" (ISP) Service 2. Information Support to Fire Recovery/Reconstruction Phase" (ISR) Service This service is already at an advanced stage having completed the first year of activity. During this time several products have been consolidated: seasonal fuel maps; daily and seasonal fire hazard maps; seasonal risk maps; prescribed fire maps. This paper aims at presenting the preliminary results of the research activity carried out in the framework of the PREFER project, focusing, in particular, on these recalled above. As for Fire Risk and Hazard assessment, many indexes have been developed in the last years. Hardly any of them uses data derived from satellite images. The FPI index is an exception to this rule which, in addition, makes use of meteorological data. In spite of being a very complete index, the FPI still allows room for improvement which justify the interest of PREFER in it. PREFER's innovative approach to FPI will allow taking into account the effect of solar illumination conditions in determining the humidity present in the dead vegetation, and therefore its proneness to burn. PREFER innovation also focus in allowing the index to

  5. Right putamen and age are the most discriminant features to diagnose Parkinson's disease by using 123I-FP-CIT brain SPET data by using an artificial neural network classifier, a classification tree (ClT).

    Science.gov (United States)

    Cascianelli, S; Tranfaglia, C; Fravolini, M L; Bianconi, F; Minestrini, M; Nuvoli, S; Tambasco, N; Dottorini, M E; Palumbo, B

    2017-01-01

    The differential diagnosis of Parkinson's disease (PD) and other conditions, such as essential tremor and drug-induced parkinsonian syndrome or normal aging brain, represents a diagnostic challenge. 123 I-FP-CIT brain SPET is able to contribute to the differential diagnosis. Semiquantitative analysis of radiopharmaceutical uptake in basal ganglia (caudate nuclei and putamina) is very useful to support the diagnostic process. An artificial neural network classifier using 123 I-FP-CIT brain SPET data, a classification tree (CIT), was applied. CIT is an automatic classifier composed of a set of logical rules, organized as a decision tree to produce an optimised threshold based classification of data to provide discriminative cut-off values. We applied a CIT to 123 I-FP-CIT brain SPET semiquantitave data, to obtain cut-off values of radiopharmaceutical uptake ratios in caudate nuclei and putamina with the aim to diagnose PD versus other conditions. We retrospectively investigated 187 patients undergoing 123 I-FP-CIT brain SPET (Millenium VG, G.E.M.S.) with semiquantitative analysis performed with Basal Ganglia (BasGan) V2 software according to EANM guidelines; among them 113 resulted affected by PD (PD group) and 74 (N group) by other non parkinsonian conditions, such as Essential Tremor and drug-induced PD. PD group included 113 subjects (60M and 53F of age: 60-81yrs) having Hoehn and Yahr score (HY): 0.5-1.5; Unified Parkinson Disease Rating Scale (UPDRS) score: 6-38; N group included 74 subjects (36M and 38 F range of age 60-80 yrs). All subjects were clinically followed for at least 6-18 months to confirm the diagnosis. To examinate data obtained by using CIT, for each of the 1,000 experiments carried out, 10% of patients were randomly selected as the CIT training set, while the remaining 90% validated the trained CIT, and the percentage of the validation data correctly classified in the two groups of patients was computed. The expected performance of an "average

  6. Mutation in the Drosophila melanogaster adenosine receptor gene selectively decreases the mosaic hyperplastic epithelial outgrowth rates in wts or dco heterozygous flies

    Czech Academy of Sciences Publication Activity Database

    Sidorov, Roman; Kučerová, Lucie; Kiss, I.; Žurovec, Michal

    2015-01-01

    Roč. 11, č. 1 (2015), s. 95-105 ISSN 1573-9538 R&D Projects: GA ČR GA14-27816S EU Projects: European Commission(CZ) FP7/2007-2013 Program:FP7 Institutional support: RVO:60077344 Keywords : cell competition * Adgf-A * Ent2 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.196, year: 2015 http://link.springer.com/article/10.1007%2Fs11302-014-9435-2

  7. Recent advances on green concrete for structural purposes the contribution of the EU-FP7 project EnCoRe

    CERN Document Server

    Ferrara, Liberato; Martinelli, Enzo

    2017-01-01

    This book is mainly based on the results of the EU-funded UE-FP7 Project EnCoRe, which aimed to characterize the key physical and mechanical properties of a novel class of advanced cement-based materials incorporating recycled powders and aggregates and/or natural ingredients in order to allow partial or even total replacement of conventional constituents. More specifically, the project objectives were to predict the physical and mechanical performance of concrete with recycled aggregates; to understand the potential contribution of recycled fibers as a dispersed reinforcement in concrete matrices; and to demonstrate the feasibility and possible applications of natural fibers as a reinforcement in cementitious composites. All of these aspects are fully covered in the book. The opening chapters explain the material concept and design and discuss the experimental characterization of the physical, chemical, and mechanical properties of the recycled raw constituents, as well as of the cementitious composite incor...

  8. FP-LAPW calculations of the elastic, electronic and thermoelectric properties of the filled skutterudite CeRu4Sb12

    International Nuclear Information System (INIS)

    Shankar, A.; Rai, D.P.; Chettri, Sandeep; Khenata, R.; Thapa, R.K.

    2016-01-01

    We have investigated the electronic structure, elastic and thermoelectric properties of the filled skutterudite CeRu 4 Sb 12 using the density functional theory (DFT). The full potential linearized augmented plane wave (FP-LAPW) method within a framework of the generalized gradient approximation (GGA) approach is used to perform the calculations presented here. The electronic structure calculation suggests an indirect band gap semiconducting nature of the material with energy band gap of 0.08 eV. The analysis of the elastic constants at relaxed positions reveals the ductile nature of the sample material with covalent contribution in the inter-atomic bonding. The narrow band gap semiconducting nature with high value of Seebeck coefficient suggests the possibility of the thermoelectric application of the material. The analysis of the thermal transport properties confirms the result obtained from the energy band structure of the material with high thermopower and dimensionless figure of merit 0.19 at room temperature.

  9. β-Adrenergic receptor-mediated suppression of interleukin 2 receptors in human lymphocytes

    International Nuclear Information System (INIS)

    Feldman, R.D.; Hunninghake, G.W.; McArdle, W.L.

    1987-01-01

    Adrenergic receptor agonists are know to attenuate the proliferative response of human lymphocytes after activation; however, their mechanism of action is unknown. Since expression of interleukin 2 (IL-2) receptors is a prerequisite for proliferation, the effect of β-adrenergic receptor agonists on lymphocyte IL-2 receptors was studied on both mitogen-stimulated lymphocytes and IL-2-dependent T lymphocyte cell lines. In both cell types the β-adrenergic receptor agonist isoproterenol blocked the expression of IL-2 receptors, as determined with the IL-2 receptor anti-TAC antibody. To determine the effect of β-adrenergic agonists on expression of the high affinity IL-2 receptors, [ 125 I]IL-2 binding studies were performed at concentrations selective for high affinity sites. No significant effect of β-adrenergic agonists on high affinity IL-2 receptor sites could be detected. The data demonstrate that β-adrenergic receptor agonists down-regulate IL-2 receptors primarily affecting low affinity sites

  10. Quantitative receptor radioautography in the study of receptor-receptor interactions in the nucleus tractus solitarii

    Directory of Open Access Journals (Sweden)

    Fior-Chadi D.R.

    1998-01-01

    Full Text Available The nucleus tractus solitarii (NTS in the dorsomedial medulla comprises a wide range of neuropeptides and biogenic amines. Several of them are related to mechanisms of central blood pressure control. Angiotensin II (Ang II, neuropeptide Y (NPY and noradrenaline (NA are found in the NTS cells, as well as their receptors. Based on this observation we have evaluated the modulatory effect of these peptide receptors on a2-adrenoceptors in the NTS. Using quantitative receptor radioautography, we observed that NPY and Ang II receptors decreased the affinity of a2-adrenoceptors for their agonists in the NTS of the rat. Cardiovascular experiments agreed with the in vitro data. Coinjection of a threshold dose of Ang II or of the NPY agonists together with an ED50 dose of adrenergic agonists such as NA, adrenaline and clonidine counteracted the depressor effect produced by the a2-agonist in the NTS. The results provide evidence for the existence of an antagonistic interaction between Ang II at1 receptors and NPY receptor subtypes with the a2-adrenoceptors in the NTS. This receptor interaction may reduce the transduction over the a2-adrenoceptors which can be important in central cardiovascular regulation and in the development of hypertension

  11. Baking reduces prostaglandin, resolvin, and hydroxy-fatty acid content of farm-raised Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Raatz, Susan K; Golovko, Mikhail Y; Brose, Stephen A; Rosenberger, Thad A; Burr, Gary S; Wolters, William R; Picklo, Matthew J

    2011-10-26

    The consumption of seafood enriched in n-3 polyunsaturated fatty acids (PUFA) is associated with a decreased risk of cardiovascular disease. Several n-3 oxidation products from eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (22:6n-3) have known protective effects in the vasculature. It is not known whether the consumption of cooked seafood enriched in n-3 PUFA causes appreciable consumption of lipid oxidation products. We tested the hypothesis that baking Atlantic salmon (Salmo salar) increases the level of n-3 and n-6 PUFA oxidation products over raw salmon. We measured the contents of several monohydroxy-fatty acids (MHFA), prostanoids, and resolvins. Our data demonstrate that baking did not change the overall total levels of MHFA. However, baking resulted in selective regioisomeric loss of hydroxy fatty acids from arachidonic acid (20:4n-6) and EPA, while significantly increasing hydroxyl-linoleic acid levels. The contents of prostanoids and resolvins were reduced several-fold with baking. The inclusion of a coating on the salmon prior to baking reduced the loss of some MHFA but had no effect on prostanoid losses incurred by baking. Baking did not decrease n-3 PUFA contents, indicating that baking of salmon is an acceptable means of preparation that does not alter the potential health benefits of high n-3 seafood consumption. The extent to which the levels of MHFA, prostanoids, and resolvins in the raw or baked fish have physiologic consequence for humans needs to be determined.

  12. Synthesis of unlabelled, 3H- and 125I-labelled β-CIT and its ω-fluoroalkyl analogues β-CIT-FE and β-CIT-FP, including synthesis of precursors

    International Nuclear Information System (INIS)

    Swahn, C.-G.; Halldin, Christer; Guenther, Ilonka; Patt, Joerg; Ametamey, Simon

    1996-01-01

    The full synthesis of the cocaine congener 2β-carbomethoxy-3β-(4-iodophenyl)tropane β-CIT) and its N-fluoroalkyl analogues, fluoroethyl- and fluoropropyl-nor-β-CIT (β-CIT-FE and β-CIT-FP) starting from cocaine is described. The synthetic routes include the preparation of precursors for labelling with radionuclides such as 11 C, 18 F, 76 Br, 123 I, 125 I and 3 H. Here we also report the labelling with 125 I or 3 H for use in autoradiographic examination of human brain sections. (author)

  13. Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling

    Science.gov (United States)

    Yang, Hongwei; Tang, Ya-ping; Sun, Hao; Song, Yunping; Chen, Chu

    2013-01-01

    SUMMARY Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here we show that synaptic and cognitive impairments following repeated exposure to Δ9-tetrahydrocannabinol (Δ9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids, in the brain. COX-2 induction by Δ9-THC is mediated via CB1 receptor-coupled G-protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks down-regulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ9-THC exposures. Ablation of COX-2 also eliminates Δ9-THC-impaired hippocampal long-term synaptic plasticity, spatial, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ9-THC in Alzheimer’s disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2. PMID:24267894

  14. XMRV: usage of receptors and potential co-receptors

    Directory of Open Access Journals (Sweden)

    Gaddam Durga

    2011-09-01

    Full Text Available Abstract Background XMRV is a gammaretrovirus first identified in prostate tissues of Prostate Cancer (PC patients and later in the blood cells of patients with Chronic Fatigue Syndrome (CFS. Although XMRV is thought to use XPR1 for cell entry, it infects A549 cells that do not express XPR1, suggesting usage of other receptors or co-receptors. Methods To study the usage of different receptors and co- receptors that could play a role in XMRV infection of lymphoid cells and GHOST (GFP- Human osteosarcoma cells expressing CD4 along with different chemokine receptors including CCR1, CCR2, etc., were infected with XMRV. Culture supernatants and cells were tested for XMRV replication using real time quantitative PCR. Results Infection and replication of XMRV was seen in a variety of GHOST cells, LNCaP, DU145, A549 and Caski cell lines. The levels of XMRV replication varied in different cell lines showing differential replication in different cell lines. However, replication in A549 which lacks XPR1 expression was relatively higher than DU145 but lower than, LNCaP. XMRV replication varied in GHOST cell lines expressing CD4 and each of the co- receptors CCR1-CCR8 and bob. There was significant replication of XMRV in CCR3 and Bonzo although it is much lower when compared to DU145, A549 and LNCaP. Conclusion XMRV replication was observed in GHOST cells that express CD4 and each of the chemokine receptors ranging from CCR1- CCR8 and BOB suggesting that infectivity in hematopoietic cells could be mediated by use of these receptors.

  15. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  16. GABA receptor imaging

    International Nuclear Information System (INIS)

    Lee, Jong Doo

    2007-01-01

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA A -receptor that allows chloride to pass through a ligand gated ion channel and GABA B -receptor that uses G-proteins for signaling. The GABA A -receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA A -receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11 C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18 F-fluoroflumazenil (FFMZ) has been developed to overcome 11 C's short half-life. 18 F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1 1 C-FMZ PET instead of 18 F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA A receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas

  17. An outcome of nuclear safety research in JAERI. Case study for LOCA, FP, criticality and reprocessing

    International Nuclear Information System (INIS)

    Yanagisawa, Kazuaki; Ito, Keishiro; Kawashima, Kei; Katsuki, Chisato; Shirabe, Masashi

    2009-09-01

    An outcome of nuclear safety research done by JAERI was case studied by the bibliometric method. (1) For LOCA (loss-of-coolant accident) a domestic share of JAERI in monoclinic research paper was 63% at the past (20) 1978-1982 but was decreased to 40% at the present 1998-2002. For co-authored papers a domestic share between JAERI and PS (public sectors) is almost zero at past (20) but increased to 4% at the present. Research cooperation is active between Tokyo University and JAERI or between JAERI and Nagoya University. (2) Project-type research is to have a large monopolization in papers and that of basic-type research is to have a large development of research networking (DRN). (3) For FP, a share of co-authored paper is high due to an enhanced cooperation among JAERI-PO (Public Organization)-PS. For criticality, research activity was enhanced after JCO accident, especially at NUCEF. (4) For reprocessing, PS had a monopolistic position with a domestic share of 71% and a share of JAERI was about 20%. (5) LOCA and RIA outputs born by NSR-JAERI coincided partly to those of the Safety Licensing Guidelines but a share of contribution done by JAERI was ambiguous due to the lack of necessary information. (author)

  18. Some problems in utilization system of FP nuclides and actinides in the high level liquid wastes

    International Nuclear Information System (INIS)

    Ichiyanagi, Katsuaki; Emura, Satoru

    1974-01-01

    There are three nuclides of sup(134/137)Cs for irradiation sources, 90 Sr for radioisotope thermoelectric generators, and 238 Pu for cardiac pacemakers, as the nuclides for which considerable demand is expected in near future among those contained in reprocessed high level liquid wastes. Technical problems are first described from the viewpoint of utilization system. Then the control system of reprocessed high level wastes is expained. Finally, economic possibility and problems in their utilization are discussed. Being in competition with 60 Co, the price of sup(134/137)Cs will be lower than that of 60 Co after a decade. The annual demand in 1985 may be 6.1 x 10 6 Ci. The conclusive factor of 90 Sr market price is hard to get because it finds no strong competitive nuclides. It may be about 20 yen/Ci after ten years. Demand is expected to be approximately 1.2 x 10 7 Ci/year. However it is pretty hard to pay the cost of group separation and solidification, storage and conversion to products with such gain. It is estimated that the balance of income and outgo would be almost profitable, if the utilization of FP nuclides would progress and the demand three times as large as this assumption would be developed. (Wakatsuki, Y.)

  19. FP-(LAPW + lo study of mechanical stability and electronic behavior of CoGe in B20 structure

    Directory of Open Access Journals (Sweden)

    Timaoui M. A.

    2017-10-01

    Full Text Available The aim of this work is a theoretical study of structural, elastic, electronic and thermal properties of CoGe compound in B20 structure using All-electron self-consistent Full Potential Augmented Plane Waves plus local orbital “FP(LAPW + lo” within the framework of Density Functional Theory DFT. GGA-PBEsol is the exchange-correlation potential selected in this work. This choice is motivated by the success of this functional in predicting structural and mechanical properties of solids. The values obtained by the study of structural properties are in very good agreement with those found previously. In this work, the elastic constants have been predicted for the first time and the obtained values confirm the mechanical stability of the CoGe compound in its B20 structure. The electronic part of this work shows that CoGe has metallic behavior with a mixed bonding between cobalt and germanium of covalent-metallic type. The effect of temperature and hydrostatic pressure on the lattice parameter - a0, heat capacity at constant volume - CV, thermal expansion coefficient - α and entropy - S of the CoGe have been studied using Debye model.

  20. The two-state dimer receptor model: a general model for receptor dimers.

    Science.gov (United States)

    Franco, Rafael; Casadó, Vicent; Mallol, Josefa; Ferrada, Carla; Ferré, Sergi; Fuxe, Kjell; Cortés, Antoni; Ciruela, Francisco; Lluis, Carmen; Canela, Enric I

    2006-06-01

    Nonlinear Scatchard plots are often found for agonist binding to G-protein-coupled receptors. Because there is clear evidence of receptor dimerization, these nonlinear Scatchard plots can reflect cooperativity on agonist binding to the two binding sites in the dimer. According to this, the "two-state dimer receptor model" has been recently derived. In this article, the performance of the model has been analyzed in fitting data of agonist binding to A(1) adenosine receptors, which are an example of receptor displaying concave downward Scatchard plots. Analysis of agonist/antagonist competition data for dopamine D(1) receptors using the two-state dimer receptor model has also been performed. Although fitting to the two-state dimer receptor model was similar to the fitting to the "two-independent-site receptor model", the former is simpler, and a discrimination test selects the two-state dimer receptor model as the best. This model was also very robust in fitting data of estrogen binding to the estrogen receptor, for which Scatchard plots are concave upward. On the one hand, the model would predict the already demonstrated existence of estrogen receptor dimers. On the other hand, the model would predict that concave upward Scatchard plots reflect positive cooperativity, which can be neither predicted nor explained by assuming the existence of two different affinity states. In summary, the two-state dimer receptor model is good for fitting data of binding to dimeric receptors displaying either linear, concave upward, or concave downward Scatchard plots.

  1. First direct fluorescence polarization assay for the detection and quantification of spirolides in mussel samples

    International Nuclear Information System (INIS)

    Otero, Paz; Alfonso, Amparo; Alfonso, Carmen; Araoz, Romulo; Molgo, Jordi; Vieytes, Mercedes R.; Botana, Luis M.

    2011-01-01

    Highlights: → A direct assay based in the binding of nAChR to spirolide toxins by FP is described. → A direct relationship between FP and 13-desMeC in the range of 10-500 nM is obtained. → FP is dependent on the 13, 19-didesMeC in a higher concentration range than 13-desMeC. → FP assay is a sensitive method to detect and quantify 13-desMeC in mussel samples. - Abstract: In 2009, we achieve the first inhibition FP assay to detect imine cyclic toxins. In the present paper we propose a new FP assay for direct quantify spirolides. This new method has resulted in significant improvement of sensitivity, rapidity and accessibility. In the method design, nicotinic acetylcholine receptor from Torpedo marmorata membranes labelled with a derivative of fluorescein was used. Spirolides, 13-desmethyl spirolide C (13-desMeC) and 13,19-didesmethyl spirolide C (13,19-didesMeC) were extracted and purified from cultures of the Alexandrium ostenfeldii dinoflagellate. Data showed the decrease of FP when toxin concentration was increased. Thus, a relationship between the FP units and the spirolides amount present in a sample was obtained. This direct assay is a reproducible, simple and very sensitive method with a detection limit about 25 nM for 13-desMeC and 150 nM for 13,19-didesMeC. The procedure was used to measure spirolides in mussel samples using an extraction and clean up protocol suitable for the FP assay. Results obtained show that this method is able to quantify 13-desMeC in the range of 50-350 μg kg -1 meat. Other liposoluble toxins did not interfere with the assay, proving a specific method. Moreover, the matrix do not affect in the range of toxin concentrations that involving risk of spirolides intoxication.

  2. First direct fluorescence polarization assay for the detection and quantification of spirolides in mussel samples

    Energy Technology Data Exchange (ETDEWEB)

    Otero, Paz; Alfonso, Amparo [Departamento de Farmacologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario s/n, 27002 Lugo (Spain); Alfonso, Carmen [CIFGA Laboratorio, Plaza de Santo Domingo, 1, 27001 Lugo (Spain); Araoz, Romulo; Molgo, Jordi [CNRS, Institut de Neurobiologie Alfred Fessard - FRC2118, Laboratoire de Neurobiologie et Developpement UPR3294, 1 Avenue de la Terrasse, 91198 Gif sur Yvette Cedex (France); Vieytes, Mercedes R. [Departamento de Fisiologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo (Spain); Botana, Luis M., E-mail: luis.botana@usc.es [Departamento de Farmacologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario s/n, 27002 Lugo (Spain)

    2011-09-09

    Highlights: {yields} A direct assay based in the binding of nAChR to spirolide toxins by FP is described. {yields} A direct relationship between FP and 13-desMeC in the range of 10-500 nM is obtained. {yields} FP is dependent on the 13, 19-didesMeC in a higher concentration range than 13-desMeC. {yields} FP assay is a sensitive method to detect and quantify 13-desMeC in mussel samples. - Abstract: In 2009, we achieve the first inhibition FP assay to detect imine cyclic toxins. In the present paper we propose a new FP assay for direct quantify spirolides. This new method has resulted in significant improvement of sensitivity, rapidity and accessibility. In the method design, nicotinic acetylcholine receptor from Torpedo marmorata membranes labelled with a derivative of fluorescein was used. Spirolides, 13-desmethyl spirolide C (13-desMeC) and 13,19-didesmethyl spirolide C (13,19-didesMeC) were extracted and purified from cultures of the Alexandrium ostenfeldii dinoflagellate. Data showed the decrease of FP when toxin concentration was increased. Thus, a relationship between the FP units and the spirolides amount present in a sample was obtained. This direct assay is a reproducible, simple and very sensitive method with a detection limit about 25 nM for 13-desMeC and 150 nM for 13,19-didesMeC. The procedure was used to measure spirolides in mussel samples using an extraction and clean up protocol suitable for the FP assay. Results obtained show that this method is able to quantify 13-desMeC in the range of 50-350 {mu}g kg{sup -1} meat. Other liposoluble toxins did not interfere with the assay, proving a specific method. Moreover, the matrix do not affect in the range of toxin concentrations that involving risk of spirolides intoxication.

  3. 聚吡咯-酰基吡唑啉酮复合膜修饰玻碳电极测定酚磺乙胺的研究%Electrochemical Behavior and Determination of Ethamsylate on Poly-pyrrole/HPMαFP Complex Film Coated Glassy Carbon Electrode

    Institute of Scientific and Technical Information of China (English)

    韩慧; 李锦州; 孙仁霞

    2012-01-01

    报道了一种新型聚吡咯-酰基吡唑啉酮复合膜修饰玻碳电极(Ppy/HPMαFP/GCE)对酚磺乙胺(ETH)电化学性质及其反应机理的研究.酚磺乙胺的电化学性质检测运用循环伏安法和脉冲伏安法.实验表明,与裸GCE和Ppy/GCE相比,Ppy/HPM α FP/GCE修饰电极对酚磺乙胺有良好的催化作用.聚吡咯与酰基吡唑啉酮产生了协同增效作用.在pH=5.5的磷酸盐(PBS)缓冲溶液中,该修饰电极测试ETH的CV曲线于0.35V和0.4V出现一对灵敏的氧化还原峰,峰电位差△Ep较裸玻碳电极降低510mV,比Ppy修饰电极降低100mV,峰电流显著增加.在最佳条件下,氧化峰电流与ETH浓度于2.0×10-6~1.0×10-4mol·L-1范围内呈现良好的线性关系,检出限为6.0×10-7mol·L-1.%In this paper, a novel voltammetric method using poly-pyrrole and acyl-pyrazolone composite film modified glassy carton electrode (Ppy /HPMaFP /CCE) was developed for studying the electrochemical behavior and reaction mechanism of ethamsylate. The electrochemical parameters of ethamsylate were investigated by cyclic voltammetry and differential pulse voltammetry. Compared to the bare GCE and Ppy /GCE, the Ppy/HP-MaFP /CCE showed an excellent electro-catalytical effect on the oxidation of ethamsylate with significant increase in the peak current. The above results indicated that a synergistic effect was existed between poly-pyrrole and HPMaFP. According to the experiment, In PBS buffer solution with a pH of 5.5, a pair of sensitive redox peaks with Epa=0.40V, Epc=0.35V(vs.SCE) was obtained on the PPyHPMaFP modified electrode. The difference of peak potentials(△ Ep) was 510mV which was lower than on bare glassy carbon electrode, and about 100mV lower than on Ppy modified electrode. Meanwhile, the peak current markedly increased. Under the optimum conditions, linear calibration curve was obtained in the concentration range of2.0×10-6 ~1.0×10-4 mol·L-1. The detection limit was 6.0×10-7 mol·L-1.

  4. Selexipag in the treatment of pulmonary arterial hypertension: design, development, and therapy

    Directory of Open Access Journals (Sweden)

    Hardin EA

    2016-11-01

    Full Text Available Elizabeth Ashley Hardin,1 Kelly M Chin2 1Department of Internal Medicine, Division of Cardiology, 2Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA Abstract: Pulmonary arterial hypertension is characterized by abnormalities in the small pulmonary arteries including increased vasoconstriction, vascular remodeling, proliferation of smooth muscle cells, and in situ thrombosis. Selexipag, a novel, oral prostacyclin receptor agonist, has been shown to improve hemodynamics in a phase II clinical trial and reduce clinical worsening in a large phase III clinical trial involving patients with pulmonary arterial hypertension. In this paper, we describe the prostacyclin signaling pathway, currently available oral prostanoid medications, and the development and clinical use of selexipag. Keywords: selexipag, pulmonary arterial hypertension, prostacyclin

  5. The impact of reconstruction and scanner characterisation on the diagnostic capability of a normal database for [(123)I]FP-CIT SPECT imaging

    DEFF Research Database (Denmark)

    Dickson, John C; Tossici-Bolt, Livia; Sera, Terez

    2017-01-01

    for scan normality using the ENC-DAT normal database obtained in well-documented healthy subjects. Patient and normal data were reconstructed with iterative reconstruction with correction for attenuation, scatter and septal penetration (ACSC), the same reconstruction without corrections (IRNC......), and filtered back-projection (FBP) with data quantified using small volume-of-interest (VOI) (BRASS) and large VOI (Southampton) analysis methods. Test performance was assessed with and without system characterisation, using receiver operating characteristics (ROC) analysis for age-independent data and using......BACKGROUND: The use of a normal database for [(123)I]FP-CIT SPECT imaging has been found to be helpful for cases which are difficult to interpret by visual assessment alone, and to improve reproducibility in scan interpretation. The aim of this study was to assess whether the use of different...

  6. Carbonate Precipitates During Heat Evolution in FP-Type Cells

    International Nuclear Information System (INIS)

    Bruce L. Cain

    2000-01-01

    In previous work, we reported measurement of large amounts of heat generated during experiments using an FP-type open cell with concentrated LiOH/D 2 O electrolytes and thin-film Pd cathodes. During the heat evolution in several runs, which produced >100 W for more than 20 h, we consistently observed the concomitant evolution of gases from the electrolyte and the precipitation of large amounts of lithium carbonate. The carbonate production was clearly visible during production of heat, creating an opaque electrolyte even during long periods with no electrolysis current. These results indicated an unusual chemical reaction, either catalyzed by the heating process or possibly creating the heat itself. The total energy released during the earlier experiments was ∼7 MJ, while the heat of formation for the lithium carbonate in the cell was only 0.8 MJ. Hence, only ∼10% of the heat signatures from these experiments can be attributed to the precipitate formation, the balance of the heat presumably arising from nonchemical sources in the cells. The earlier experiments that produced heat also suffered from problems of reproducibility, with only 5 of 38 runs producing any heat at all. The unsuccessful runs also did not produce precipitates, and the only gas produced in these cells was due to the normal electrolysis of D 2 O to produce oxygen and deuterium in the electrodes. Recent work has focused on recreating the chemical precipitation reaction, in efforts to understand and/or trigger the heat production process. With findings from these experiments, new experiments were conducted using larger (1 L LiOH/D 2 O) cells with Pt anodes and Pd film cathodes immersed but left open-circuited. After the addition of H 2 O 2 , and subsequent heating and cooling, these cells visually reproduced the precipitation and gas evolution of the earlier heat-producing runs. However, these new runs only produced a few watts of power for several minutes, consistent with the normal exothermal

  7. Receptor oligomerization in family B1 of G-protein-coupled receptors

    DEFF Research Database (Denmark)

    Roed, Sarah Norklit; Ørgaard, Anne; Jørgensen, Rasmus

    2012-01-01

    , the glucagon receptor, and the receptors for parathyroid hormone (PTHR1 and PTHR2). The dysregulation of several family B1 receptors is involved in diseases, such as diabetes, chronic inflammation, and osteoporosis which underlines the pathophysiological importance of this GPCR subfamily. In spite of this......, investigation of family B1 receptor oligomerization and especially its pharmacological importance is still at an early stage. Even though GPCR oligomerization is a well-established phenomenon, there is a need for more investigations providing a direct link between these interactions and receptor functionality......The superfamily of the seven transmembrane G-protein-coupled receptors (7TM/GPCRs) is the largest family of membrane-associated receptors. GPCRs are involved in the pathophysiology of numerous human diseases, and they constitute an estimated 30-40% of all drug targets. During the last two decades...

  8. Activation of glucocorticoid receptors increases 5-HT2A receptor levels

    DEFF Research Database (Denmark)

    Trajkovska, Viktorija; Kirkegaard, Lisbeth; Krey, Gesa

    2009-01-01

    an effect of GR activation on 5-HT2A levels, mature organotypic hippocampal cultures were exposed to corticosterone with or without GR antagonist mifepristone and mineralocorticoid receptor (MR) antagonist spironolactone. In GR under-expressing mice, hippocampal 5-HT2A receptor protein levels were decreased......Major depression is associated with both dysregulation of the hypothalamic pituitary adrenal axis and serotonergic deficiency, not the least of the 5-HT2A receptor. However, how these phenomena are linked to each other, and whether a low 5-HT2A receptor level is a state or a trait marker...... of depression is unknown. In mice with altered glucocorticoid receptor (GR) expression we investigated 5-HT2A receptor levels by Western blot and 3H-MDL100907 receptor binding. Serotonin fibre density was analyzed by stereological quantification of serotonin transporter immunopositive fibers. To establish...

  9. Low blood flow at onset of moderate intensity exercise does not limit muscle oxygen uptake

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Mortensen, Stefan Peter; Saltin, Bengt

    2010-01-01

    The effect of low blood flow at onset of moderate intensity exercise on the rate of rise in muscle oxygen uptake was examined. Seven male subjects performed a 3.5 minute one-legged knee-extensor exercise bout (24+/-1 (+/-S.D.) W) without (CON) and with (double blockade; DB) arterial infusion of i....... Additionally, prostanoids and/or NO appear to play important roles in elevating skeletal muscle blood flow in the initial phase of exercise. Key words: Oxygen delivery, oxygen extraction, nitric oxide, prostanoids.......The effect of low blood flow at onset of moderate intensity exercise on the rate of rise in muscle oxygen uptake was examined. Seven male subjects performed a 3.5 minute one-legged knee-extensor exercise bout (24+/-1 (+/-S.D.) W) without (CON) and with (double blockade; DB) arterial infusion...... of inhibitors of nitric oxide synthase (NOS; L-NMMA) and cyclooxygenase (COX; indomethacin) in order to inhibit the synthesis of nitric oxide (NO) and prostanoids, respectively.. Leg blood flow and leg oxygen delivery throughout exercise was 25-50 % lower (P

  10. Gβ promotes pheromone receptor polarization and yeast chemotropism by inhibiting receptor phosphorylation.

    Science.gov (United States)

    Ismael, Amber; Tian, Wei; Waszczak, Nicholas; Wang, Xin; Cao, Youfang; Suchkov, Dmitry; Bar, Eli; Metodiev, Metodi V; Liang, Jie; Arkowitz, Robert A; Stone, David E

    2016-04-12

    Gradient-directed cell migration (chemotaxis) and growth (chemotropism) are processes that are essential to the development and life cycles of all species. Cells use surface receptors to sense the shallow chemical gradients that elicit chemotaxis and chemotropism. Slight asymmetries in receptor activation are amplified by downstream signaling systems, which ultimately induce dynamic reorganization of the cytoskeleton. During the mating response of budding yeast, a model chemotropic system, the pheromone receptors on the plasma membrane polarize to the side of the cell closest to the stimulus. Although receptor polarization occurs before and independently of actin cable-dependent delivery of vesicles to the plasma membrane (directed secretion), it requires receptor internalization. Phosphorylation of pheromone receptors by yeast casein kinase 1 or 2 (Yck1/2) stimulates their internalization. We showed that the pheromone-responsive Gβγ dimer promotes the polarization of the pheromone receptor by interacting with Yck1/2 and locally inhibiting receptor phosphorylation. We also found that receptor phosphorylation is essential for chemotropism, independently of its role in inducing receptor internalization. A mathematical model supports the idea that the interaction between Gβγ and Yck1/2 results in differential phosphorylation and internalization of the pheromone receptor and accounts for its polarization before the initiation of directed secretion. Copyright © 2016, American Association for the Advancement of Science.

  11. Glucocorticoid receptor modulators.

    Science.gov (United States)

    Meijer, Onno C; Koorneef, Lisa L; Kroon, Jan

    2018-06-01

    The glucocorticoid hormone cortisol acts throughout the body to support circadian processes and adaptation to stress. The glucocorticoid receptor is the target of cortisol and of synthetic glucocorticoids, which are used widely in the clinic. Both agonism and antagonism of the glucocorticoid receptor may be beneficial in disease, but given the wide expression of the receptor and involvement in various processes, beneficial effects are often accompanied by unwanted side effects. Selective glucocorticoid receptor modulators are ligands that induce a receptor conformation that allows activation of only a subset of downstream signaling pathways. Such molecules thereby combine agonistic and antagonistic properties. Here we discuss the mechanisms underlying selective receptor modulation and their promise in treating diseases in several organ systems where cortisol signaling plays a role. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  12. Angiotensin type 2 receptor (AT2R) and receptor Mas

    DEFF Research Database (Denmark)

    Villela, Daniel; Leonhardt, Julia; Patel, Neal

    2015-01-01

    The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striki...

  13. Comparison of two neural network classifiers in the differential diagnosis of essential tremor and Parkinson's disease by 123I-FP-CIT brain SPECT

    International Nuclear Information System (INIS)

    Palumbo, Barbara; Fravolini, Mario Luca; Nuvoli, Susanna; Spanu, Angela; Madeddu, Giuseppe; Paulus, Kai Stephan; Schillaci, Orazio

    2010-01-01

    To contribute to the differentiation of Parkinson's disease (PD) and essential tremor (ET), we compared two different artificial neural network classifiers using 123 I-FP-CIT SPECT data, a probabilistic neural network (PNN) and a classification tree (ClT). 123 I-FP-CIT brain SPECT with semiquantitative analysis was performed in 216 patients: 89 with ET, 64 with PD with a Hoehn and Yahr (H and Y) score of ≤2 (early PD), and 63 with PD with a H and Y score of ≥2.5 (advanced PD). For each of the 1,000 experiments carried out, 108 patients were randomly selected as the PNN training set, while the remaining 108 validated the trained PNN, and the percentage of the validation data correctly classified in the three groups of patients was computed. The expected performance of an ''average performance PNN'' was evaluated. In analogy, for ClT 1,000 classification trees with similar structures were generated. For PNN, the probability of correct classification in patients with early PD was 81.9±8.1% (mean±SD), in patients with advanced PD 78.9±8.1%, and in ET patients 96.6±2.6%. For ClT, the first decision rule gave a mean value for the putamen of 5.99, which resulted in a probability of correct classification of 93.5±3.4%. This means that patients with putamen values >5.99 were classified as having ET, while patients with putamen values <5.99 were classified as having PD. Furthermore, if the caudate nucleus value was higher than 6.97 patients were classified as having early PD (probability 69.8±5.3%), and if the value was <6.97 patients were classified as having advanced PD (probability 88.1%±8.8%). These results confirm that PNN achieved valid classification results. Furthermore, ClT provided reliable cut-off values able to differentiate ET and PD of different severities. (orig.)

  14. A search for presynaptic inhibitory histamine receptors in guinea-pig tissues: Further H3 receptors but no evidence for H4 receptors.

    Science.gov (United States)

    Petri, Doris; Schlicker, Eberhard

    2016-07-01

    The histamine H4 receptor is coupled to Gi/o proteins and expressed on inflammatory cells and lymphoid tissues; it was suggested that this receptor also occurs in the brain or on peripheral neurones. Since many Gi/o protein-coupled receptors, including the H3 receptor, serve as presynaptic inhibitory receptors, we studied whether the sympathetic neurones supplying four peripheral tissues and the cholinergic neurones in the hippocampus from the guinea-pig are equipped with release-modulating H4 and H3 receptors. For this purpose, we preincubated tissue pieces from the aorta, atrium, renal cortex and vas deferens with (3)H-noradrenaline and hippocampal slices with (3)H-choline and determined the electrically evoked tritium overflow. The stimulation-evoked overflow in the five superfused tissues was inhibited by the muscarinic receptor agonist oxotremorine, which served as a positive control, but not affected by the H4 receptor agonist 4-methylhistamine. The H3 receptor agonist R-α-methylhistamine inhibited noradrenaline release in the peripheral tissues without affecting acetylcholine release in the hippocampal slices. Thioperamide shifted the concentration-response curve of histamine in the aorta and the renal cortex to the right, yielding apparent pA2 values of 8.0 and 8.1, respectively, which are close to its affinity at other H3 receptors but higher by one log unit than its pKi at the H4 receptor of the guinea-pig. In conclusion, histamine H4 receptors could not be identified in five experimental models of the guinea-pig that are suited for the detection of presynaptic inhibitory receptors whereas H3 receptors could be shown in the peripheral tissues but not in the hippocampus. This article is part of the Special Issue entitled 'Histamine Receptors'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Real-Time G-Protein-Coupled Receptor Imaging to Understand and Quantify Receptor Dynamics

    Directory of Open Access Journals (Sweden)

    María S. Aymerich

    2011-01-01

    Full Text Available Understanding the trafficking of G-protein-coupled receptors (GPCRs and their regulation by agonists and antagonists is fundamental to develop more effective drugs. Optical methods using fluorescent-tagged receptors and spinning disk confocal microscopy are useful tools to investigate membrane receptor dynamics in living cells. The aim of this study was to develop a method to characterize receptor dynamics using this system which offers the advantage of very fast image acquisition with minimal cell perturbation. However, in short-term assays photobleaching was still a problem. Thus, we developed a procedure to perform a photobleaching-corrected image analysis. A study of short-term dynamics of the long isoform of the dopamine type 2 receptor revealed an agonist-induced increase in the mobile fraction of receptors with a rate of movement of 0.08 μm/s For long-term assays, the ratio between the relative fluorescence intensity at the cell surface versus that in the intracellular compartment indicated that receptor internalization only occurred in cells co-expressing G protein-coupled receptor kinase 2. These results indicate that the lateral movement of receptors and receptor internalization are not directly coupled. Thus, we believe that live imaging of GPCRs using spinning disk confocal image analysis constitutes a powerful tool to study of receptor dynamics.

  16. Knock-In Mice with NOP-eGFP Receptors Identify Receptor Cellular and Regional Localization.

    Science.gov (United States)

    Ozawa, Akihiko; Brunori, Gloria; Mercatelli, Daniela; Wu, Jinhua; Cippitelli, Andrea; Zou, Bende; Xie, Xinmin Simon; Williams, Melissa; Zaveri, Nurulain T; Low, Sarah; Scherrer, Grégory; Kieffer, Brigitte L; Toll, Lawrence

    2015-08-19

    The nociceptin/orphanin FQ (NOP) receptor, the fourth member of the opioid receptor family, is involved in many processes common to the opioid receptors including pain and drug abuse. To better characterize receptor location and trafficking, knock-in mice were created by inserting the gene encoding enhanced green fluorescent protein (eGFP) into the NOP receptor gene (Oprl1) and producing mice expressing a functional NOP-eGFP C-terminal fusion in place of the native NOP receptor. The NOP-eGFP receptor was present in brain of homozygous knock-in animals in concentrations somewhat higher than in wild-type mice and was functional when tested for stimulation of [(35)S]GTPγS binding in vitro and in patch-clamp electrophysiology in dorsal root ganglia (DRG) neurons and hippocampal slices. Inhibition of morphine analgesia was equivalent when tested in knock-in and wild-type mice. Imaging revealed detailed neuroanatomy in brain, spinal cord, and DRG and was generally consistent with in vitro autoradiographic imaging of receptor location. Multicolor immunohistochemistry identified cells coexpressing various spinal cord and DRG cellular markers, as well as coexpression with μ-opioid receptors in DRG and brain regions. Both in tissue slices and primary cultures, the NOP-eGFP receptors appear throughout the cell body and in processes. These knock-in mice have NOP receptors that function both in vitro and in vivo and appear to be an exceptional tool to study receptor neuroanatomy and correlate with NOP receptor function. The NOP receptor, the fourth member of the opioid receptor family, is involved in pain, drug abuse, and a number of other CNS processes. The regional and cellular distribution has been difficult to determine due to lack of validated antibodies for immunohistochemical analysis. To provide a new tool for the investigation of receptor localization, we have produced knock-in mice with a fluorescent-tagged NOP receptor in place of the native NOP receptor. These

  17. Receptor assay

    Energy Technology Data Exchange (ETDEWEB)

    Kato, K; Ibayashi, H [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1975-05-01

    This paper summarized present status and problems of analysis of hormone receptor and a few considerations on clinical significance of receptor abnormalities. It was pointed that in future clinical field quantitative and qualitative analysis of receptor did not remain only in the etiological discussion, but that it was an epoch-making field of investigation which contained the possiblity of artificial change of sensitivity of living body on drugs and the development connected directly with treatment of various diseases.

  18. NBS for Drought risks reduction in the Algarve (Portugal): selected achievements from PT FCT ProWaterMan and from EU FP7 MARSOL projects

    Science.gov (United States)

    Lobo-Ferreira, João-Paulo

    2017-04-01

    Southern Europe and the Mediterranean region are facing the challenge of managing its water resources under conditions of increasing scarcity and/or floods, besides concerns about water quality. Innovative water management strategies with nature-based solutions, such as the storage of excess water during floods, in Managed Aquifer Recharge (MAR) schemes can greatly decrease the risk of floods while it increases water availability for future use, eventually in drought periods. The Algarve region is the southern most region of Portugal mainland. It has an area of 4,997 km2 and about 451 thousand permanent inhabitants. Selected achievements of two research projects (Portugal FCT sponsored ProWaterMan project and EU FP7 sponsored MARSOL project), will be addressed regarding the Campina de Faro and Querença-Silves aquifers in the Algarve. In Faro, the idea of harvesting rainwater from the greenhouse rooftops and using this water to recharge aquifers is not new. However, using this NbS as a climate mitigation and adaptation tool with the overall impact and wide range of benefits is a step forward in innovative methodologies. This NbS can have particular positive impacts in Mediterranean conditions with (new) precipitation patterns, more intense but less frequent. The potential greenhouses surface area of about 2.74 km2 can be used by connecting these infrastructures to several large wells aiming to infiltrate an amount of 1.63 hm3/year of harvested water. There is a strong support from the Portuguese Water Agency (Agência Portuguesa do Ambiente, I.P., Algarve branch), the Water Supplier and Wastewater (Águas do Algarve, S.A.), and the local farmers and land owners which have frequent flood and/or drought problems, represented by HUBEL (a SME that produces most greenhouses for Faro area) in this project. During EU 7FP INO-DEMO MARSOL project, a survey about protection and preservation of groundwater was conducted with a sample of Portuguese farmers of the Algarve

  19. Calcitonin and calcitonin receptor-like receptors: common themes with family B GPCRs?

    Science.gov (United States)

    Barwell, James; Gingell, Joseph J; Watkins, Harriet A; Archbold, Julia K; Poyner, David R; Hay, Debbie L

    2012-05-01

    The calcitonin receptor (CTR) and calcitonin receptor-like receptor (CLR) are two of the 15 human family B (or Secretin-like) GPCRs. CTR and CLR are of considerable biological interest as their pharmacology is moulded by interactions with receptor activity-modifying proteins. They also have therapeutic relevance for many conditions, such as osteoporosis, diabetes, obesity, lymphatic insufficiency, migraine and cardiovascular disease. In light of recent advances in understanding ligand docking and receptor activation in both the family as a whole and in CLR and CTR specifically, this review reflects how applicable general family B GPCR themes are to these two idiosyncratic receptors. We review the main functional domains of the receptors; the N-terminal extracellular domain, the juxtamembrane domain and ligand interface, the transmembrane domain and the intracellular C-terminal domain. Structural and functional findings from the CLR and CTR along with other family B GPCRs are critically appraised to gain insight into how these domains may function. The ability for CTR and CLR to interact with receptor activity-modifying proteins adds another level of sophistication to these receptor systems but means careful consideration is needed when trying to apply generic GPCR principles. This review encapsulates current thinking in the realm of family B GPCR research by highlighting both conflicting and recurring themes and how such findings relate to two unusual but important receptors, CTR and CLR. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  20. FP-LAPW calculations of the elastic, electronic and thermoelectric properties of the filled skutterudite CeRu{sub 4}Sb{sub 12}

    Energy Technology Data Exchange (ETDEWEB)

    Shankar, A., E-mail: amitshan2009@gmail.com [Condensed Matter Theory Group, Department of Physics, Mizoram University, 796004 (India); Rai, D.P. [Department of Physics, Pachhunga University College, Aizawl 796001 (India); Chettri, Sandeep [Condensed Matter Theory Group, Department of Physics, Mizoram University, 796004 (India); Khenata, R. [Laboratoire de Physique Quantique et de Modélisation Mathématique (LPQ3M), Département de Technologie, Université de Mascara, 29000 (Algeria); Thapa, R.K. [Condensed Matter Theory Group, Department of Physics, Mizoram University, 796004 (India)

    2016-08-15

    We have investigated the electronic structure, elastic and thermoelectric properties of the filled skutterudite CeRu{sub 4}Sb{sub 12} using the density functional theory (DFT). The full potential linearized augmented plane wave (FP-LAPW) method within a framework of the generalized gradient approximation (GGA) approach is used to perform the calculations presented here. The electronic structure calculation suggests an indirect band gap semiconducting nature of the material with energy band gap of 0.08 eV. The analysis of the elastic constants at relaxed positions reveals the ductile nature of the sample material with covalent contribution in the inter-atomic bonding. The narrow band gap semiconducting nature with high value of Seebeck coefficient suggests the possibility of the thermoelectric application of the material. The analysis of the thermal transport properties confirms the result obtained from the energy band structure of the material with high thermopower and dimensionless figure of merit 0.19 at room temperature.

  1. Molecular modeling of ligand-receptor interactions in the OR5 olfactory receptor.

    Science.gov (United States)

    Singer, M S; Shepherd, G M

    1994-06-02

    Olfactory receptors belong to the superfamily of seven transmembrane domain, G protein-coupled receptors. In order to begin analysis of mechanisms of receptor activation, a computer model of the OR5 olfactory receptor has been constructed and compared with other members of this superfamily. We have tested docking of the odor molecule lyral, which is known to activate the OR5 receptor. The results point to specific ligand-binding residues on helices III through VII that form a binding pocket in the receptor. Some of these residues occupy sequence positions identical to ligand-binding residues conserved among other superfamily members. The results provide new insights into possible molecular mechanisms of odor recognition and suggest hypotheses to guide future experimental studies using site-directed mutagenesis.

  2. Exposure to fine particulate matter in the air alters placental structure and the renin-angiotensin system.

    Directory of Open Access Journals (Sweden)

    Sônia de Fátima Soto

    Full Text Available Female Wistar rats were exposed to filtered air (F or to concentrated fine particulate matter (P for 15 days. After mating, the rats were divided into four groups and again exposed to F or P (FF, FP, PF, PP beginning on day 6 of pregnancy. At embryonic day 19, the placenta was collected. The placental structure, the protein and gene expression of TGFβ1, VEGF-A, and its receptor Flk-1 and RAS were evaluated by indirect ELISA and quantitative real-time PCR.Exposure to P decreased the placental mass, size, and surface area as well as the TGFβ1, VEGF-A and Flk-1 content. In the maternal portion of the placenta, angiotensin II (AngII and its receptors AT1 (AT1R and AT2 (AT2R were decreased in the PF and PP groups. In the fetal portion of the placenta, AngII in the FP, PF and PP groups and AT2R in the PF and PP groups were decreased, but AT1R was increased in the FP group. VEGF-A gene expression was lower in the PP group than in the FF group.Exposure to pollutants before and/or during pregnancy alters some characteristics of the placenta, indicating a possible impairment of trophoblast invasion and placental angiogenesis with possible consequences for the maternal-fetal interaction, such as a limitation of fetal nutrition and growth.

  3. Pulmonary Arterial Hypertension in Adults: Novel Drugs and Catheter Ablation Techniques Show Promise? Systematic Review on Pharmacotherapy and Interventional Strategies

    Directory of Open Access Journals (Sweden)

    Salvatore Rosanio

    2014-01-01

    Full Text Available This systematic review aims to provide an update on pharmacological and interventional strategies for the treatment of pulmonary arterial hypertension in adults. Currently US Food and Drug Administration approved drugs including prostanoids, endothelin-receptor antagonists, phosphodiesterase type-5 inhibitors, and soluble guanylate-cyclase stimulators. These agents have transformed the prognosis for pulmonary arterial hypertension patients from symptomatic improvements in exercise tolerance ten years ago to delayed disease progression today. On the other hand, percutaneous balloon atrioseptostomy by using radiofrequency perforation, cutting balloon dilatation, or insertion of butterfly stents and pulmonary artery catheter-based denervation, both associated with very low rate of major complications and death, should be considered in combination with specific drugs at an earlier stage rather than late in the progression of pulmonary arterial hypertension and before the occurrence of overt right-sided heart failure.

  4. Receptor downregulation and desensitization enhance the information processing ability of signalling receptors

    Directory of Open Access Journals (Sweden)

    Resat Haluk

    2007-11-01

    Full Text Available Abstract Background In addition to initiating signaling events, the activation of cell surface receptors also triggers regulatory processes that restrict the duration of signaling. Acute attenuation of signaling can be accomplished either via ligand-induced internalization of receptors (endocytic downregulation or via ligand-induced receptor desensitization. These phenomena have traditionally been viewed in the context of adaptation wherein the receptor system enters a refractory state in the presence of sustained ligand stimuli and thereby prevents the cell from over-responding to the ligand. Here we use the epidermal growth factor receptor (EGFR and G-protein coupled receptors (GPCR as model systems to respectively examine the effects of downregulation and desensitization on the ability of signaling receptors to decode time-varying ligand stimuli. Results Using a mathematical model, we show that downregulation and desensitization mechanisms can lead to tight and efficient input-output coupling thereby ensuring synchronous processing of ligand inputs. Frequency response analysis indicates that upstream elements of the EGFR and GPCR networks behave like low-pass filters with the system being able to faithfully transduce inputs below a critical frequency. Receptor downregulation and desensitization increase the filter bandwidth thereby enabling the receptor systems to decode inputs in a wider frequency range. Further, system-theoretic analysis reveals that the receptor systems are analogous to classical mechanical over-damped systems. This analogy enables us to metaphorically describe downregulation and desensitization as phenomena that make the systems more resilient in responding to ligand perturbations thereby improving the stability of the system resting state. Conclusion Our findings suggest that in addition to serving as mechanisms for adaptation, receptor downregulation and desensitization can play a critical role in temporal information

  5. Quality and clinical supply considerations of Paediatric Investigation Plans for IV preparations-A case study with the FP7 CloSed project.

    Science.gov (United States)

    Hanning, Sara M; Orlu Gul, Mine; Winslade, Jackie; Baarslag, Manuel A; Neubert, Antje; Tuleu, Catherine

    2016-09-25

    A Paediatric Investigation Plan (PIP) is a development plan that aims to ensure that sufficient data are obtained through studies in paediatrics to support the generation of marketing authorisation of medicines for children. This paper highlights some practical considerations and challenges with respect to PIP submissions and paediatric clinical trials during the pharmaceutical development phase, using the FP7-funded Clonidine for Sedation of Paediatric Patients in the Intensive Care Unit (CloSed) project as a case study. Examples discussed include challenges and considerations regarding formulation development, blinding and randomisation, product labelling and shipment and clinical trial requirements versus requirements for marketing authorisation. A significant quantity of information is required for PIP submissions and it is hoped that future applicants may benefit from an insight into some critical considerations and challenges faced in the CloSed project. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Modulating Estrogen Receptor-related Receptor-α Activity Inhibits Cell Proliferation*

    OpenAIRE

    Bianco, Stéphanie; Lanvin, Olivia; Tribollet, Violaine; Macari, Claire; North, Sophie; Vanacker, Jean-Marc

    2009-01-01

    High expression of the estrogen receptor-related receptor (ERR)-α in human tumors is correlated to a poor prognosis, suggesting an involvement of the receptor in cell proliferation. In this study, we show that a synthetic compound (XCT790) that modulates the activity of ERRα reduces the proliferation of various cell lines and blocks the G1/S transition of the cell cycle in an ERR...

  7. Receptor binding properties and antinociceptive effects of chimeric peptides consisting of a micro-opioid receptor agonist and an ORL1 receptor antagonist.

    Science.gov (United States)

    Kawano, Susumu; Ito, Risa; Nishiyama, Miharu; Kubo, Mai; Matsushima, Tomoko; Minamisawa, Motoko; Ambo, Akihiro; Sasaki, Yusuke

    2007-07-01

    Receptor binding properties and antinociceptive activities of chimeric peptides linked by spacers were investigated. The peptides consisted of the micro-opioid receptor ligand dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH(2)) or its analog YRFB (Tyr-D-Arg-Phe-betaAla-NH(2)) linked to the ORL1 receptor ligand Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) (Ac-RYYRIK-NH(2)). All chimeric peptides were found to possess high receptor binding affinities for both micro-opioid and ORL1 receptors in mouse brain membranes although their binding affinities for both receptors in spinal membranes were significantly lower. Among them, chimeric peptide 2, which consists of dermorphin and Ac-RYYRIK-NH(2) connected by a long spacer, had the highest binding affinity towards both receptors. In the tail-flick test following intrathecal (i.t.) administration to mice, all chimeric peptides showed potent and dose-dependent antinociceptive activities with an ED(50) of 1.34-4.51 (pmol/mouse), nearly comparable to dermorphin alone (ED(50); 1.08 pmol/mouse). In contrast to their micro-opioid receptor binding profiles, intracerebroventricular (i.c.v.) administration of the chimeric peptides resulted in much less potent antinociceptive activity (ED(50) 5.55-100peptides, and the regulation of mu-opioid receptor-mediated antinociception in brain. The present chimeric peptides may be useful as pharmacological tools for studies on micro-opioid receptor/ORL1 receptor heterodimers.

  8. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  9. EC FP6 Siberia-focused Enviro-RISKS Project and its Outcomes

    Science.gov (United States)

    Baklanov, A. A.; Gordov, E. P.

    2009-04-01

    The FP6 Project "Man-induced Environmental Risks: Monitoring, Management and Remediation of Man-made Changes in Siberia" (Enviro-RISKS) strategic objective is to facilitate elaboration of solid scientific background and understanding of man-made associated environmental risks, their influence on all aspects of regional environment and optimal ways for it remediation by means of coordinated initiatives of a range of relevant RTD projects as well as to achieve their improved integration thus giving the projects additional synergy in current activities and potential for practical applications. List of Partners includes 3 leading European research organizations, 6 leading Russian research organizations (5 - located in Siberia) and 1 organization from Kazakhstan. Additionally several Russian and European research organizations joined to the Project as Associated Partners. Scientific background and foundation for the project performance is formed by a number of different levels RTD projects carried out by Partners and devoted to near all aspects of the theme. The set comprise coordinated/performed by partners EC funded thematic international projects, Russian national projects and other projects performed by NIS partners. Project outcomes include, in particular, development and support of the bilingual Enviro-RISKS web portal (http://risks.scert.ru/) as the major tool for disseminations of environmental information and project results; achieved level of development of Siberia Integrated Regional Study (SIRS, http://sirs.scert.ru/), which is the Siberia-focused NEESPI Environmental Mega-Project ongoing under the auspices of the Siberian Branch of the Russian Academy of Sciences. The main Project outcome are Memorandum on the state of the art of environmental RTD activity in Siberia and Recommendations on future environmental RTD activity in Siberia elaborated by four Working Experts Groups working in most important for Siberia Thematic Focuses. Three Thematic Focuses

  10. Cocaine Inhibits Dopamine D2 Receptor Signaling via Sigma-1-D2 Receptor Heteromers

    Science.gov (United States)

    Navarro, Gemma; Moreno, Estefania; Bonaventura, Jordi; Brugarolas, Marc; Farré, Daniel; Aguinaga, David; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carmen; Ferre, Sergi

    2013-01-01

    Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor) can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain. PMID:23637801

  11. Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2

    Energy Technology Data Exchange (ETDEWEB)

    Kuwasako, Kenji, E-mail: kuwasako@fc.miyazaki-u.ac.jp [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kitamura, Kazuo; Nagata, Sayaka; Hikosaka, Tomomi [Division of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kato, Johji [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

    2010-02-12

    Receptor activity-modifying protein 2 (RAMP2) enables calcitonin receptor-like receptor (CRLR) to form an adrenomedullin (AM)-specific receptor. Here we investigated the function of the cytoplasmic C-terminal tail (C-tail) of human (h)CRLR by co-transfecting its C-terminal mutants into HEK-293 cells stably expressing hRAMP2. Deleting the C-tail from CRLR disrupted AM-evoked cAMP production or receptor internalization, but did not affect [{sup 125}I]AM binding. We found that CRLR residues 428-439 are required for AM-evoked cAMP production, though deleting this region had little effect on receptor internalization. Moreover, pretreatment with pertussis toxin (100 ng/mL) led to significant increases in AM-induced cAMP production via wild-type CRLR/RAMP2 complexes. This effect was canceled by deleting CRLR residues 454-457, suggesting Gi couples to this region. Flow cytometric analysis revealed that CRLR truncation mutants lacking residues in the Ser/Thr-rich region extending from Ser{sup 449} to Ser{sup 467} were unable to undergo AM-induced receptor internalization and, in contrast to the effect on wild-type CRLR, overexpression of GPCR kinases-2, -3 and -4 failed to promote internalization of CRLR mutants lacking residues 449-467. Thus, the hCRLR C-tail is crucial for AM-evoked cAMP production and internalization of the CRLR/RAMP2, while the receptor internalization is dependent on the aforementioned GPCR kinases, but not Gs coupling.

  12. Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors.

    Science.gov (United States)

    Linares, Andrea; Couling, Leena E; Carrera, Eduardo J; Speth, Robert C

    2016-06-07

    This protocol describes receptor binding patterns for Angiotensin II (Ang II) in the rat brain using a radioligand specific for Ang II receptors to perform receptor autoradiographic mapping. Tissue specimens are harvested and stored at -80 °C. A cryostat is used to coronally section the tissue (brain) and thaw-mount the sections onto charged slides. The slide-mounted tissue sections are incubated in (125)I-SI-Ang II to radiolabel Ang II receptors. Adjacent slides are separated into two sets: 'non-specific binding' (NSP) in the presence of a receptor saturating concentration of non-radiolabeled Ang II, or an AT1 Ang II receptor subtype (AT1R) selective Ang II receptor antagonist, and 'total binding' with no AT1R antagonist. A saturating concentration of AT2 Ang II receptor subtype (AT2R) antagonist (PD123319, 10 µM) is also present in the incubation buffer to limit (125)I-SI-Ang II binding to the AT1R subtype. During a 30 min pre-incubation at ~22 °C, NSP slides are exposed to 10 µM PD123319 and losartan, while 'total binding' slides are exposed to 10 µM PD123319. Slides are then incubated with (125)I-SI-Ang II in the presence of PD123319 for 'total binding', and PD123319 and losartan for NSP in assay buffer, followed by several 'washes' in buffer, and water to remove salt and non-specifically bound radioligand. The slides are dried using blow-dryers, then exposed to autoradiography film using a specialized film and cassette. The film is developed and the images are scanned into a computer for visual and quantitative densitometry using a proprietary imaging system and a spreadsheet. An additional set of slides are thionin-stained for histological comparisons. The advantage of using receptor autoradiography is the ability to visualize Ang II receptors in situ, within a section of a tissue specimen, and anatomically identify the region of the tissue by comparing it to an adjacent histological reference section.

  13. Expression of GABAergic receptors in mouse taste receptor cells.

    Directory of Open Access Journals (Sweden)

    Margaret R Starostik

    Full Text Available BACKGROUND: Multiple excitatory neurotransmitters have been identified in the mammalian taste transduction, with few studies focused on inhibitory neurotransmitters. Since the synthetic enzyme glutamate decarboxylase (GAD for gamma-aminobutyric acid (GABA is expressed in a subset of mouse taste cells, we hypothesized that other components of the GABA signaling pathway are likely expressed in this system. GABA signaling is initiated by the activation of either ionotropic receptors (GABA(A and GABA(C or metabotropic receptors (GABA(B while it is terminated by the re-uptake of GABA through transporters (GATs. METHODOLOGY/PRINCIPAL FINDINGS: Using reverse transcriptase-PCR (RT-PCR analysis, we investigated the expression of different GABA signaling molecules in the mouse taste system. Taste receptor cells (TRCs in the circumvallate papillae express multiple subunits of the GABA(A and GABA(B receptors as well as multiple GATs. Immunocytochemical analyses examined the distribution of the GABA machinery in the circumvallate papillae. Both GABA(A-and GABA(B- immunoreactivity were detected in the peripheral taste receptor cells. We also used transgenic mice that express green fluorescent protein (GFP in either the Type II taste cells, which can respond to bitter, sweet or umami taste stimuli, or in the Type III GAD67 expressing taste cells. Thus, we were able to identify that GABAergic receptors are expressed in some Type II and Type III taste cells. Mouse GAT4 labeling was concentrated in the cells surrounding the taste buds with a few positively labeled TRCs at the margins of the taste buds. CONCLUSIONS/SIGNIFICANCE: The presence of GABAergic receptors localized on Type II and Type III taste cells suggests that GABA is likely modulating evoked taste responses in the mouse taste bud.

  14. Effect of Dietary Docosahexaenoic Acid Supplementation on the Participation of Vasodilator Factors in Aorta from Orchidectomized Rats.

    Directory of Open Access Journals (Sweden)

    Diva M Villalpando

    Full Text Available Benefits of n-3 polyunsaturated fatty acids (PUFAs against cardiovascular diseases have been reported. Vascular tone regulation is largely mediated by endothelial factors whose release is modulated by sex hormones. Since the incidence of cardiovascular pathologies has been correlated with decreased levels of sex hormones, the aim of this study was to analyze whether a diet supplemented with the specific PUFA docosahexaenoic acid (DHA could prevent vascular changes induced by an impaired gonadal function. For this purpose, control and orchidectomized rats were fed with a standard diet supplemented with 5% (w/w sunflower oil or with 3% (w/w sunflower oil plus 2% (w/w DHA. The lipid profile, the blood pressure, the production of prostanoids and nitric oxide (NO, and the redox status of biological samples from control and orchidectomized rats, fed control or DHA-supplemented diet, were analyzed. The vasodilator response and the contribution of NO, prostanoids and hyperpolarizing mechanisms were also studied. The results showed that orchidectomy negatively affected the lipid profile, increased the production of prostanoids and reactive oxygen species (ROS, and decreased NO production and the antioxidant capacity, as well as the participation of hyperpolarizing mechanisms in the vasodilator responses. The DHA-supplemented diet of the orchidectomized rats decreased the release of prostanoids and ROS, while increasing NO production and the antioxidant capacity, and it also improved the lipid profile. Additionally, it restored the participation of hyperpolarizing mechanisms by activating potassium. Since the modifications induced by the DHA-supplemented diet were observed in the orchidectomized, but not in the healthy group, DHA seems to exert cardioprotective effects in physiopathological situations in which vascular dysfunction exists.

  15. Learning from the experience: preliminary results of integration experiments within PRE-EARTHQUAKES EU-FP7 Project.

    Science.gov (United States)

    Tramutoli, V.; Inan, S.; Jakowski, N.; Pulinets, S.; Romanov, A.; Filizzola, C.; Shagimuratov, I.; Pergola, N.; Genzano, N.; Lisi, M.; Alparslan, E.; Wilken, V.; Tsybulia, K.; Romanov, A.; Paciello, R.; Balasco, M.; Zakharenkova, I.; Ouzounov, D.; Papadopoulos, G. A.; Parrot, M.

    2012-04-01

    PRE-EARTHQUAKES (Processing Russian and European EARTH observations for earthQUAKE precursors Studies) EU-FP7 project is devoted to demonstrate - integrating different observational data, comparing and improving different data analysis methods - how it is possible to progressively increase reliability of short term seismic risk assessment. Three main testing area were selected (Italy, Turkey and Sakhalin ) in order to concentrate observations and integration efforts starting with a learning phase on selected event in the past devoted to identify the most suitable parameters, observations technologies, data analysis algorithms. To this aim events offering major possibilities (variety) of integration were particularly considered - Abruzzo EQ (April 6th 2009 Mw 6.3) for Italy, Elazig EQ (March 8th 2010 Mw 6.1) for Turkey and Nevelsk EQ (August 2nd 2007 Mw 6.2) for Sakhalin - without excluding other significant events occurred during 2011 like the ones of Tōhoku in Japan and Van in Turkey. For these events, different ground (80 radon and 29 spring water stations in Turkey region, 2 magneto-telluric in Italy) and satellite (18 different systems) based observations, 11 data analysis methods, for 7 measured parameters, have been compared and integrated. Results achieved by applying a validation/confutation approach devoted to evaluate the presence/absence of anomalous space-time transients in single and/or integrated observation time-series will be discussed also in comparison with results independently achieved by other authors.

  16. Summary of important results and SCDAP/RELAP5 analysis for OECD LOFT experiment LP-FP-2

    International Nuclear Information System (INIS)

    Coryell, E.W.

    1994-04-01

    This report summarizes significant technical findings from the LP-FP-2 Experiment sponsored by OECD. It was the second, and final, fission product experiment conducted in the Loss-of-Fluid Test (LOFT) facility at the Idaho National Engineering Laboratory. The overall technical objective of the test was to contribute to the understanding of fuel rod behavior, hydrogen generation, and fission product release, transport, and deposition during a V-sequence accident scenario that resulted in severe core damage. An 11 by 11 test bundle, comprised of 100 pre-pressurized fuel rods, 11 control rods, and 10 instrumented guide tubes, was surrounded by an insulating shroud and contained in a specially designed central fuel module, that was inserted into the LOFT reactor. The simulated transient was a V-sequence loss-of-coolant accident scenario featuring a pipe break in the low pressure injection system line attached to the hot leg of the LOFT broken loop piping. The transient was terminated by reflood of the reactor vessel when the outer wall shroud temperature reached 1517 K. With sustained fission power and heat from oxidation and metal-water reactions, elevated temperatures resulted in zircaloy melting, fuel liquefaction, material relocation, and the release of hydrogen, aerosols, and fission products. A description and evaluation of the major phenomena, based upon the response of on line instrumentation, analysis of fission product data, post-irradiation examination of the fuel bundle, and calculations using the SCDAP/RELAP5 computer code, are presented

  17. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

  18. A2A-D2 receptor-receptor interaction modulates gliotransmitter release from striatal astrocyte processes.

    Science.gov (United States)

    Cervetto, Chiara; Venturini, Arianna; Passalacqua, Mario; Guidolin, Diego; Genedani, Susanna; Fuxe, Kjell; Borroto-Esquela, Dasiel O; Cortelli, Pietro; Woods, Amina; Maura, Guido; Marcoli, Manuela; Agnati, Luigi F

    2017-01-01

    Evidence for striatal A2A-D2 heterodimers has led to a new perspective on molecular mechanisms involved in schizophrenia and Parkinson's disease. Despite the increasing recognition of astrocytes' participation in neuropsychiatric disease vulnerability, involvement of striatal astrocytes in A2A and D2 receptor signal transmission has never been explored. Here, we investigated the presence of D2 and A2A receptors in isolated astrocyte processes prepared from adult rat striatum by confocal imaging; the effects of receptor activation were measured on the 4-aminopyridine-evoked release of glutamate from the processes. Confocal analysis showed that A2A and D2 receptors were co-expressed on the same astrocyte processes. Evidence for A2A-D2 receptor-receptor interactions was obtained by measuring the release of the gliotransmitter glutamate: D2 receptors inhibited the glutamate release, while activation of A2A receptors, per se ineffective, abolished the effect of D2 receptor activation. The synthetic D2 peptide VLRRRRKRVN corresponding to the receptor region involved in electrostatic interaction underlying A2A-D2 heteromerization abolished the ability of the A2A receptor to antagonize the D2 receptor-mediated effect. Together, the findings are consistent with heteromerization of native striatal astrocytic A2A-D2 receptors that via allosteric receptor-receptor interactions could play a role in the control of striatal glutamatergic transmission. These new findings suggest possible new pathogenic mechanisms and/or therapeutic approaches to neuropsychiatric disorders. © 2016 International Society for Neurochemistry.

  19. EUTEMPE-RX, an EC supported FP7 project for the training and education of medical physics experts in radiology

    International Nuclear Information System (INIS)

    Bosmans, H.; Van Peteghem, N.; Bliznakova, K.; Vassileva, J.; Padovani, R.; Christofides, S.; Tsapaki, V.; Caruana, C.J.

    2015-01-01

    The core activity of the medical physics expert (MPE) is to ensure optimal use of ionising radiation in health care. It is essential that these health care professionals are trained to the highest level, defined as European Qualifications Framework for Lifelong Learning (EQF) level 8 by the European Commission's Radiation Protection Report 174 'Guidelines on the MPE'. The main objective of the EUTEMPE-RX project is to provide a model training scheme that allows the medical physicist in diagnostic and interventional radiology (D and IR) to reach this high level. A European network of partners was brought together in this FP7 EC project to ensure sufficient expertise in all aspects of the subject and to create a harmonised course programme. Targeted participants are medical physicists in D and IR in hospitals, engineers and scientists in medical device industries and officers working in regulatory authorities. Twelve course modules will be developed at EQF level 8, with radiation safety and diagnostic effectiveness being prevalent subjects. The modules will combine online with face-to-face teaching using a blended learning approach. (authors)

  20. N-glycosylation of the β2 adrenergic receptor regulates receptor function by modulating dimerization.

    Science.gov (United States)

    Li, Xiaona; Zhou, Mang; Huang, Wei; Yang, Huaiyu

    2017-07-01

    N-glycosylation is a common post-translational modification of G-protein-coupled receptors (GPCRs). However, it remains unknown how N-glycosylation affects GPCR signaling. β 2 adrenergic receptor (β 2 AR) has three N-glycosylation sites: Asn6, Asn15 at the N-terminus, and Asn187 at the second extracellular loop (ECL2). Here, we show that deletion of the N-glycan did not affect receptor expression and ligand binding. Deletion of the N-glycan at the N-terminus rather than Asn187 showed decreased effects on isoproterenol-promoted G-protein-dependent signaling, β-arrestin2 recruitment, and receptor internalization. Both N6Q and N15Q showed decreased receptor dimerization, while N187Q did not influence receptor dimerization. As decreased β 2 AR homodimer accompanied with reduced efficiency for receptor function, we proposed that the N-glycosylation of β 2 AR regulated receptor function by influencing receptor dimerization. To verify this hypothesis, we further paid attention to the residues at the dimerization interface. Studies of Lys60 and Glu338, two residues at the receptor dimerization interface, exhibited that the K60A/E338A showed decreased β 2 AR dimerization and its effects on receptor signaling were similar to N6Q and N15Q, which further supported the importance of receptor dimerization for receptor function. This work provides new insights into the relationship among glycosylation, dimerization, and function of GPCRs. Peptide-N-glycosidase F (PNGase F, EC 3.2.2.11); endo-β-N-acetylglucosaminidase A (Endo-A, EC 3.2.1.96). © 2017 Federation of European Biochemical Societies.

  1. Prognostic Value of Estrogen Receptor alpha and Progesterone Receptor Conversion in Distant Breast Cancer Metastases

    NARCIS (Netherlands)

    Hoefnagel, Laurien D. C.; Moelans, Cathy B.; Meijer, S. L.; van Slooten, Henk-Jan; Wesseling, Pieter; Wesseling, Jelle; Westenend, Pieter J.; Bart, Joost; Seldenrijk, Cornelis A.; Nagtegaal, Iris D.; Oudejans, Joost; van der Valk, Paul; van Gils, Carla H.; van der Wall, Elsken; van Diest, Paul J.

    2012-01-01

    BACKGROUND: Changes in the receptor profile of primary breast cancers to their metastases (receptor conversion) have been described for the estrogen receptor alpha (ER alpha) and progesterone receptor (PR). The purpose of this study was to evaluate the impact of receptor conversion for ER alpha and

  2. Microarray-Based Determination of Estrogen Receptor, Progesterone Receptor, and HER2 Receptor Status in Breast Cancer

    NARCIS (Netherlands)

    Roepman, Paul; Horlings, Hugo M.; Krijgsman, Oscar; Kok, Marleen; Bueno-de-Mesquita, Jolien M.; Bender, Richard; Linn, Sabine C.; Glas, Annuska M.; van de Vijver, Marc J.

    2009-01-01

    Purpose: The level of estrogen receptor (ER), progesterone receptor (PR), and HER2 aids in the determination of prognosis and treatment of breast cancer. Immunohistochemistry is currently the predominant method for assessment, but differences in methods and interpretation can substantially affect

  3. Sustainable introduction of GM crops into european agriculture: a summary report of the FP6 SIGMEA research project*

    Directory of Open Access Journals (Sweden)

    Messéan Antoine

    2009-01-01

    Full Text Available In 2003, the European Commission established the principle of coexistence which refers to “the ability of farmers to make a practical choice between conventional, organic and GM-crop production, in compliance with the legal obligations for labelling and/or purity standards” and laid down guidelines defining the context of this coexistence1. In order to determine what is needed for the sustainable introduction of GM crops in Europe, the cross-disciplinary SIGMEA Research Project was set up to create a science-based framework to inform decision-makers. SIGMEA has (i collated and analysed European data on gene flow and the environmental impacts of the major crop species which are likely to be transgenic in the future (maize, rapeseed, sugar beet, rice, and wheat, (ii designed predictive models of gene flow at the landscape level, (iii analysed the technical feasibility and economic impacts of coexistence in the principal farming regions of Europe, (iv developed novel GMO detection methods, (v addressed legal issues related to coexistence, and (vi proposed public and farm scale decisionmaking tools, as well as guidelines regarding management and governance. This publishable version of the final activity report of the FP6 SIGMEA research project, covers the fourteen major issues under investigation.

  4. The implementation of the Open Access paradigm to the EC-FP7 MED-SUV (Mediterranean Supersite Volcanoes) project

    Science.gov (United States)

    Puglisi, Giuseppe; Brito, Fabrice; Caumont, Hervé; D'Auria, Luca; Fernandez, José; Mazzetti, Paolo; Mathieu, Pierre Philippe; Nativi, Stefano; Papeschi, Fabrizio; Pepe, Antonio; Reitano, Danilo; Sangianantoni, Agata; Scarpato, Giovanni; Spampinato, Letizia

    2016-04-01

    The overall goal of the EC-FP7 Mediterranean Supersite Volcanoes (MED-SUV) project is to apply the rationale of the Supersites GEO initiative to Campi Flegrei/Vesuvius and Mt. Etna to reduce the volcanic risk, by improving the understanding of the underlying geophysical processes, through the integration and sharing of the in-situ and Earth Observation (EO) data sets and the implementation of new instruments and monitoring systems. The project involves 24 EU and no-EU partners, including research and academic institutions, space agencies and SMEs. In this framework, the application of the Open Access paradigm has offered the opportunity to study and apply practical solutions concerning the data management (i.e. data polices, foreground exploitation and sustainability), intellectual property rights (i.e., ownership, licences, agreements) and technical issues (i.e., design and implementation of an interoperability e-infrastructure, access systems, etc.). This contribution presents pro and cons encountered in the project, as well as the main outcomes of the implementation of the Open Access to the Italian Supersites. This experience will be exploited in the building of international research infrastructures, such as EPOS, and the outcomes of the project will contribute to foster the Open Access to the research data in a wide context, as the GEO-GEOSS framework.

  5. An FP7 "Space" project: Aphorism "Advanced PRocedures for volcanic and Seismic Monitoring"

    Science.gov (United States)

    Di Iorio, A., Sr.; Stramondo, S.; Bignami, C.; Corradini, S.; Merucci, L.

    2014-12-01

    APHORISM project proposes the development and testing of two new methods to combine Earth Observation satellite data from different sensors, and ground data. The aim is to demonstrate that this two types of data, appropriately managed and integrated, can provide new improved GMES products useful for seismic and volcanic crisis management. The first method, APE - A Priori information for Earthquake damage mapping, concerns the generation of maps to address the detection and estimate of damage caused by a seism. The use of satellite data to investigate earthquake damages is not an innovative issue. We can find a wide literature and projects concerning such issue, but usually the approach is only based on change detection techniques and classifications algorithms. The novelty of APE relies on the exploitation of a priori information derived by InSAR time series to measure surface movements, shake maps obtained from seismological data, and vulnerability information. This a priori information is then integrated with change detection map to improve accuracy and to limit false alarms. The second method deals with volcanic crisis management. The method, MACE - Multi-platform volcanic Ash Cloud Estimation, concerns the exploitation of GEO (Geosynchronous Earth Orbit) sensor platform, LEO (Low Earth Orbit) satellite sensors and ground measures to improve the ash detection and retrieval and to characterize the volcanic ash clouds. The basic idea of MACE consists of an improvement of volcanic ash retrievals at the space-time scale by using both the LEO and GEO estimations and in-situ data. Indeed the standard ash thermal infrared retrieval is integrated with data coming from a wider spectral range from visible to microwave. The ash detection is also extended in case of cloudy atmosphere or steam plumes. APE and MACE methods have been defined in order to provide products oriented toward the next ESA Sentinels satellite missions.The project is funded under the European Union FP7

  6. Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling.

    Science.gov (United States)

    Chen, Rongqing; Zhang, Jian; Fan, Ni; Teng, Zhao-Qian; Wu, Yan; Yang, Hongwei; Tang, Ya-Ping; Sun, Hao; Song, Yunping; Chen, Chu

    2013-11-21

    Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ(9)-tetrahydrocannabinol (Δ(9)-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ(9)-THC is mediated via CB1 receptor-coupled G protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ(9)-THC exposures. Ablation of COX-2 also eliminates Δ(9)-THC-impaired hippocampal long-term synaptic plasticity, working, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ(9)-THC in Alzheimer's disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. The Orphan Nuclear Receptor TR4 Is a Vitamin A-activated Nuclear Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, X. Edward; Suino-Powell, Kelly M.; Xu, Yong; Chan, Cee-Wah; Tanabe, Osamu; Kruse, Schoen W.; Reynolds, Ross; Engel, James Douglas; Xu, H. Eric (Michigan-Med); (Van Andel)

    2015-11-30

    Testicular receptors 2 and 4 (TR2/4) constitute a subgroup of orphan nuclear receptors that play important roles in spermatogenesis, lipid and lipoprotein regulation, and the development of the central nervous system. Currently, little is known about the structural features and the ligand regulation of these receptors. Here we report the crystal structure of the ligand-free TR4 ligand binding domain, which reveals an autorepressed conformation. The ligand binding pocket of TR4 is filled by the C-terminal half of helix 10, and the cofactor binding site is occupied by the AF-2 helix, thus preventing ligand-independent activation of the receptor. However, TR4 exhibits constitutive transcriptional activity on multiple promoters, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, or ligand binding substantially reduce the transcriptional activity of this receptor. Importantly, both retinol and retinoic acid are able to promote TR4 to recruit coactivators and to activate a TR4-regulated reporter. These findings demonstrate that TR4 is a ligand-regulated nuclear receptor and suggest that retinoids might have a much wider regulatory role via activation of orphan receptors such as TR4.

  8. Soman- or kainic acid-induced convulsions decrease muscarinic receptors but not benzodiazepine receptors

    International Nuclear Information System (INIS)

    Churchill, L.; Pazdernik, T.L.; Cross, R.S.; Nelson, S.R.; Samson, F.E.

    1990-01-01

    [3H]Quinuclidinyl benzilate (QNB) binding to muscarinic receptors decreased in the rat forebrain after convulsions induced by a single dose of either soman, a potent inhibitor of acetylcholinesterase, or kainic acid, an excitotoxin. A Rosenthal plot revealed that the receptors decreased in number rather than affinity. When the soman-induced convulsions were blocked, the decrease in muscarinic receptors at 3 days was less extensive than when convulsions occurred and at 10 days they approached control levels in most of the brain areas. The most prominent decrements in QNB binding were in the piriform cortex where the decline in QNB binding is probably related to the extensive convulsion-associated neuropathology. The decrements in QNB binding after convulsions suggest that the convulsive state leads to a down-regulation of muscarinic receptors in some brain areas. In contrast to the decrease in QNB binding after convulsions, [3H]flunitrazepam binding to benzodiazepine receptors did not change even in the piriform cortex where the loss in muscarinic receptors was most prominent. Thus, it appears that those neuronal processes that bear muscarinic receptors are more vulnerable to convulsion-induced change than those with benzodiazepine receptors

  9. Plutonium and minor actinides management in thermal high - temperature reactors - the EU FP6 project puma

    International Nuclear Information System (INIS)

    Kuijper, J. C.

    2007-01-01

    The High Temperature gas-cooled Reactor (HTR) can fulfil a very useful niche for the purposes of Pu and Minor Actinide (MA) incineration due to its unique and unsurpassed safety features, as well as to the attractive incentives offered by the nature of the coated particle (CP) fuel. No European reactor of this type is currently available, but there has been, and still is, considerable interest internationally. Decisions to construct such a reactor in China and in South Africa have already been made or are about to be made. Apart from the unique and unsurpassed safety features offered by this reactor type, the nature of the CP fuel offers a number of attractive characteristics. In particular, it can withstand burn-ups far beyond that in either LWR or FR systems. Demonstrations as high as 75% FIMA have been achieved. The coated particle itself offers significantly improved proliferation resistance, and finally with a correct choice of the kernel composition, it can be a very effective support for direct geological disposal of the fuel. The overall objective of the PUMA project, a Specific Targeted Research Project (STREP) within the European Union 6th Framework (EU FP6), is to investigate the possibilities for the utilisation and transmutation of plutonium and especially minor actinides in contemporary and future (high temperature) gas-cooled reactor designs, which are promising tools for improving the sustainability of the nuclear fuel cycle. This contributes to the reduction of Pu and MA stockpiles, and also to the development of safe and sustainable reactors for CO 2 -free energy generation. A number of important issues concerning the use of Pu and MA in gas-cooled reactors have already been dealt with in other projects, or are being treated in ongoing projects, e.g. as part of EU FP6. However, further steps are required to demonstrate the potential of HTRs as Pu/MA transmuters based on realistic/feasible designs of CP Pu/MA fuel and the PUMA focuses on necessary

  10. Cooperative ethylene receptor signaling

    OpenAIRE

    Liu, Qian; Wen, Chi-Kuang

    2012-01-01

    The gaseous plant hormone ethylene is perceived by a family of five ethylene receptor members in the dicotyledonous model plant Arabidopsis. Genetic and biochemical studies suggest that the ethylene response is suppressed by ethylene receptor complexes, but the biochemical nature of the receptor signal is unknown. Without appropriate biochemical measures to trace the ethylene receptor signal and quantify the signal strength, the biological significance of the modulation of ethylene responses ...

  11. Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

    International Nuclear Information System (INIS)

    Waser, Beatrice; Reubi, Jean Claude

    2014-01-01

    Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the 125 iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer 125 I-GLP-1(7-36)amide. Receptor autoradiography studies with 125 I-GLP-1(7-36)amide agonist or 125 I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist 125 I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer 125 I-GLP-1(7-36)amide. For comparison, 125 I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with 125 I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

  12. Optoelectronic properties of XIn2S4 (X = Cd, Mg) thiospinels through highly accurate all-electron FP-LAPW method coupled with modified approximations

    International Nuclear Information System (INIS)

    Yousaf, Masood; Dalhatu, S.A.; Murtaza, G.; Khenata, R.; Sajjad, M.; Musa, A.; Rahnamaye Aliabad, H.A.; Saeed, M.A.

    2015-01-01

    Highlights: • Highly accurate all-electron FP-LAPW+lo method is used. • New physical parameters are reported, important for the fabrication of optoelectronic devices. • A comparative study that involves FP-LAPW+lo method and modified approximations. • Computed band gap values have good agreement with the experimental values. • Optoelectronic results of fundamental importance can be utilized for the fabrication of devices. - Abstract: We report the structural, electronic and optical properties of the thiospinels XIn 2 S 4 (X = Cd, Mg), using highly accurate all-electron full potential linearized augmented plane wave plus local orbital method. In order to calculate the exchange and correlation energies, the method is coupled with modified techniques such as GGA+U and mBJ-GGA, which yield improved results as compared to the previous studies. GGA+SOC approximation is also used for the first time on these compounds to examine the spin orbit coupling effect on the band structure. From the analysis of the structural parameters, robust character is predicted for both materials. Energy band structures profiles are fairly the same for GGA, GGA+SOC, GGA+U and mBJ-GGA, confirming the indirect and direct band gap nature of CdIn 2 S 4 and MgIn 2 S 4 materials, respectively. We report the trend of band gap results as: (mBJ-GGA) > (GGA+U) > (GGA) > (GGA+SOC). Localized regions appearing in the valence bands for CdIn 2 S 4 tend to split up nearly by ≈1 eV in the case of GGA+SOC. Many new physical parameters are reported that can be important for the fabrication of optoelectronic devices. Optical spectra namely, dielectric function (DF), refractive index n(ω), extinction coefficient k(ω), reflectivity R(ω), optical conductivity σ(ω), absorption coefficient α(ω) and electron loss function are discussed. Optical’s absorption edge is noted to be 1.401 and 1.782 for CdIn 2 S 4 and MgIn 2 S 4 , respectively. The prominent peaks in the electron energy spectrum

  13. Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

    International Nuclear Information System (INIS)

    Pires, L.A.; Hegg, R.; Freitas, F.R.; Tavares, E.R.; Almeida, C.P.; Baracat, E.C.; Maranhão, R.C.

    2012-01-01

    Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy

  14. Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice

    NARCIS (Netherlands)

    Hanson, Julien; Gille, Andreas; Zwykiel, Sabrina; Lukasova, Martina; Clausen, Björn E.; Ahmed, Kashan; Tunaru, Sorin; Wirth, Angela; Offermanns, Stefan

    2010-01-01

    The antidyslipidemic drug nicotinic acid and the antipsoriatic drug monomethyl fumarate induce cutaneous flushing through activation of G protein-coupled receptor 109A (GPR109A). Flushing is a troublesome side effect of nicotinic acid, but may be a direct reflection of the wanted effects of

  15. Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

    Energy Technology Data Exchange (ETDEWEB)

    Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, PO Box 62, Berne (Switzerland)

    2014-06-15

    Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the {sup 125}iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer {sup 125}I-GLP-1(7-36)amide. Receptor autoradiography studies with {sup 125}I-GLP-1(7-36)amide agonist or {sup 125}I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist {sup 125}I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer {sup 125}I-GLP-1(7-36)amide. For comparison, {sup 125}I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with {sup 125}I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

  16. Dengue virus receptor

    OpenAIRE

    Hidari, Kazuya I.P.J.; Suzuki, Takashi

    2011-01-01

    Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

  17. Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning

    NARCIS (Netherlands)

    Douma, B. R.; Korte, S. M.; Buwalda, B.; La Fleur, S. E.; Bohus, B.; Luiten, P. G.

    1998-01-01

    Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and

  18. Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning

    NARCIS (Netherlands)

    Douma, BRK; Korte, SM; Buwalda, B; la Fleur, SE; Bohus, B; Luiten, PGM

    Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and

  19. Functional relevance of G-protein-coupled-receptor-associated proteins, exemplified by receptor-activity-modifying proteins (RAMPs).

    Science.gov (United States)

    Fischer, J A; Muff, R; Born, W

    2002-08-01

    The calcitonin (CT) receptor (CTR) and the CTR-like receptor (CRLR) are close relatives within the type II family of G-protein-coupled receptors, demonstrating sequence identity of 50%. Unlike the interaction between CT and CTR, receptors for the related hormones and neuropeptides amylin, CT-gene-related peptide (CGRP) and adrenomedullin (AM) require one of three accessory receptor-activity-modifying proteins (RAMPs) for ligand recognition. An amylin/CGRP receptor is revealed when CTR is co-expressed with RAMP1. When complexed with RAMP3, CTR interacts with amylin alone. CRLR, initially classed as an orphan receptor, is a CGRP receptor when co-expressed with RAMP1. The same receptor is specific for AM in the presence of RAMP2. Together with human RAMP3, CRLR defines an AM receptor, and with mouse RAMP3 it is a low-affinity CGRP/AM receptor. CTR-RAMP1, antagonized preferentially by salmon CT-(8-32) and not by CGRP-(8-37), and CRLR-RAMP1, antagonized by CGRP-(8-37), are two CGRP receptor isotypes. Thus amylin and CGRP interact specifically with heterodimeric complexes between CTR and RAMP1 or RAMP3, and CGRP and AM interact with complexes between CRLR and RAMP1, RAMP2 or RAMP3.

  20. Pathophysiological consequences of receptor mistraffic: Tales from the platelet P2Y12 receptor.

    Science.gov (United States)

    Cunningham, Margaret R; Aungraheeta, Riyaad; Mundell, Stuart J

    2017-07-05

    Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function. Receptors include purinergic receptors (P2Y 1 and P2Y 12 ), proteinase-activated receptor (PAR1 and PAR4) and thromboxane receptors (TPα), among others. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis. With the advance of genomic technologies, there has been a substantial increase in the identification of naturally occurring rare and common GPCR variants. These variants include single-nucleotide polymorphisms (SNPs) and insertion or deletions that have the potential to alter GPCR expression or function. A number of defects in platelet GPCRs that disrupt receptor function have now been characterized in patients with mild bleeding disorders. This review will focus on rare, function-disrupting variants of platelet GPCRs with particular emphasis upon mutations in the P2Y 12 receptor gene that affect receptor traffic to modulate platelet function. Further this review will outline how the identification and characterization of function-disrupting GPCR mutations provides an essential link in translating our detailed understanding of receptor traffic and function in cell line studies into relevant human biological systems. Copyright © 2017. Published by Elsevier B.V.

  1. Summary of important results and SCDAP/RELAP5 analysis for OECD LOFT experiment LP-FP-2

    Energy Technology Data Exchange (ETDEWEB)

    Coryell, E.W. [EG and G Idaho, Inc., Idaho Falls, ID (United States)

    1994-04-01

    This report summarizes significant technical findings from the LP-FP-2 Experiment sponsored by the Organization of Economic Cooperation and Development (OECD). It was the second, and final, fission product experiment conducted in the Loss-of-Fluid Test (LOFT) facility at the Idaho National Engineering Laboratory. The overall technical objective of the test was to contribute to the understanding of fuel rod behavior, hydrogen generation, and fission product release, transport, and deposition during a V-sequence accident scenario that resulted in severe core damage. An 11 by 11 test bundle, comprised of 100 prepressurized fuel rods, 11 control rods, and 10 instrumented guide tubes, was surrounded by an insulating shroud and contained in a specially designed central fuel module, that was inserted into the LOFT reactor. The simulated transient was a V-sequence loss-of-coolant accident scenario featuring a pipe break in the low pressure injection system line attached to the hot leg of the LOFT broken loop piping. The transient was terminated by reflood of the reactor vessel when the outer wall shroud temperature reached 1517 K. With sustained fission power and heat from oxidation and metal-water reactions, elevated temperatures resulted in zircaloy melting, fuel liquefaction, material relocation, and the release of hydrogen, aerosols, and fission products. A description and evaluation of the major phenomena, based upon the response of on line instrumentation, analysis of fission product data, postirradiation examination of the fuel bundle, and calculations using the SCDAP/RELAP5 computer code, are presented.

  2. Safety analyses for sodium-cooled fast reactors with pelletized and sphere-pac oxide fuels within the FP-7 European project PELGRIMM - 15386

    International Nuclear Information System (INIS)

    Maschek, W.; Andriolo, L.; Matzerath-Boccaccini, C.; Delage, F.; Parisi, C.; Del Nevo, A.; Abbate, G.; Schmitt, D.

    2015-01-01

    The European FP-7 project PELGRIMM addresses the development of Minor-Actinide (MA) bearing oxide fuel for Sodium-cooled Fast Reactors. Optionally, both MA homogeneous recycling and heterogeneous recycling is investigated with pellet and sphere-pac fuel. A first safety assessment of sphere-pac fuelled cores should be given in the Work Package 4 of the project. This assessment is in continuity with the former FP-7 CP-ESFR project. Within the CP-ESFR project the CONF2 core design has been developed characterized by a core with a large upper sodium plenum to reduce the coolant void worth. This optimized core has been chosen for the safety analyses in PELGRIMM. The task within the PELGRIMM project is thus a safety assessment of the CONF2 core loaded either with pellets or with sphere-pac fuel. The investigations started with the design of the CONF2 core with sphere-pac fuel and the determination of core safety parameters and burn-up behavior. The neutronic analyses have been performed with the MCNPX code. Variants of the CONF2 core contain up to 4% Am in the fuel. The results revealed an extended void worth (core + upper plenum) for an Am free core of 1 up to 3 dollars for the 4% Am core. Thermal-hydraulic design analyses have been performed by RELAP5-3D. The accident simulations should be performed by different codes, some of which focus on the initiation phase of the accident, as SAS4A, BELLA and the MAT5DYN code, whereas the SIMMER-III code will also deal with the later accident phases and a potential whole core melting. The codes had to be adapted to the specifics of the sphere-pac fuel, in particular to the thermal conductivity and gap conditions. Analyses showed that the safety assessment has to take into account two main phases. Starting up the core, the green fuel shows a reduced fuel thermal conductivity. After restructuring within a couple of hours, the thermal conductivity recovers and the fuel temperature decreases. The main objective of the safety analyses

  3. Acetylcholine receptor antibody

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood of ...

  4. L-glutamate Receptor In Paramecium

    Science.gov (United States)

    Bernal-Martínez, Juan; Ortega-Soto, Arturo

    2004-09-01

    Behavioral, electrophysiological and biochemical experiments were performed in order to establish the presence of a glutamate receptor in the ciliate Paramecium. It was found that an AMPA/KA receptor is functionally expressed in Paramecium and that this receptor is immunologically and fillogenetically related to the AMPA/KA receptor present in vertebrates.

  5. Do receptors get pregnant too? Adrenergic receptor alterations in human pregnancy.

    Science.gov (United States)

    Smiley, R M; Finster, M

    1996-01-01

    In this review we discuss adrenergic receptor number and function during pregnancy, with emphasis on evidence that pregnancy results in specific receptor alterations from the nonpregnant state. Changes in adrenergic receptor function or distribution in vascular smooth muscle may be in part responsible for the decreased vascular responsiveness seen in human pregnancy, and the lack of the normal alterations may be a part of the syndromes of gestational hypertension, including preeclampsia-eclampsia. The onset of labor may be influenced by adrenergic modulation, and receptor or postreceptor level molecular alterations may trigger or facilitate normal or preterm labor. Human studies are emphasized when possible to assess the role of adrenergic signal transduction regulation in the physiology and pathophysiology of normal and complicated human pregnancy.

  6. Melatonin Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Hua Dong Yin

    2013-05-01

    Full Text Available Melatonin receptors are members of the G protein-coupled receptor (GPCR family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A and MT2 (or Mel1b or MTNR1B receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C, has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

  7. Clinical and Genomic Crosstalk between Glucocorticoid Receptor and Estrogen Receptor α In Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Jeffery M. Vahrenkamp

    2018-03-01

    Full Text Available Summary: Steroid hormone receptors are simultaneously active in many tissues and are capable of altering each other’s function. Estrogen receptor α (ER and glucocorticoid receptor (GR are expressed in the uterus, and their ligands have opposing effects on uterine growth. In endometrial tumors with high ER expression, we surprisingly found that expression of GR is associated with poor prognosis. Dexamethasone reduced normal uterine growth in vivo; however, this growth inhibition was abolished in estrogen-induced endometrial hyperplasia. We observed low genomic-binding site overlap when ER and GR are induced with their respective ligands; however, upon simultaneous induction they co-occupy more sites. GR binding is altered significantly by estradiol with GR recruited to ER-bound loci that become more accessible upon estradiol induction. Gene expression responses to co-treatment were more similar to estradiol but with additional regulated genes. Our results suggest phenotypic and molecular interplay between ER and GR in endometrial cancer. : Estrogen receptor α (ER and glucocorticoid receptor (GR are expressed in the uterus and have differential effects on growth. Vahrenkamp et al. find that expression of both receptors is associated with poor outcome in endometrial cancer and that simultaneous induction of ER and GR leads to molecular interplay between the receptors. Keywords: estrogen receptor, glucocorticoid receptor, endometrial cancer

  8. Receptor binding radiotracers for the angiotensin II receptor: radioiodinated [Sar1, Ile8]angiotensin II

    International Nuclear Information System (INIS)

    Gibson, R.E.; Beauchamp, H.T.; Fioravanti, C.; Brenner, N.; Burns, H.D.

    1994-01-01

    The potential for imaging the angiotensin II receptor was evaluated using the radioiodinated peptide antagonist [ 125 I][Sar 1 , Ile 8 ]angiotensin II. The radioligand provides a receptor-mediated signal in several tissues in rat (kidneys, adrenal and liver). The receptor-mediated signal of 3% ID/g kidney cortex should be sufficient to permit imaging, at least via SPECT. The radiotracer is sensitive to reductions in receptor concentration and can be used to define in vivo dose-occupancy curves of angiotensin II receptor ligands. Receptor-mediated images of [ 123 I][Sar 1 , Ile 8 ]angiotensin II were obtained in the rat kidney and Rhesus monkey liver. (author)

  9. Design and initial implementation of the WHO FP umbrella project- to strengthen contraceptive services in the sub Saharan Africa.

    Science.gov (United States)

    Kabra, Rita; Ali, Moazzam; Kiarie, James

    2017-06-15

    Strengthening contraceptive services in sub Saharan Africa is critical to achieve the FP 2020 goal of enabling 120 million more women and girls to access and use contraceptives by 2020 and the Sustainable Development Goals (SDG) targets of universal access to sexual and reproductive health (SRH) services including family planning by 2030. The World Health Organization (WHO) and partners have designed a multifaceted project to strengthen health systems to reduce the unmet need of contraceptive and family planning services in sub Saharan Africa. The plan leverages global, regional and national partnerships to facilitate and increase the use of evidence based WHO guidelines with a specific focus on postpartum family planning. The four key approaches undertaken are i) making WHO Guidelines adaptable & appropriate for country use ii) building capacity of WHO regional/country staff iii) providing technical support to countries and iv) strengthening partnerships for introduction and implementation of WHO guidelines. This paper describes the project design and elaborates the multifaceted approaches required in initial implementation to strengthen contraceptive services. The initial results from this project reflect that simultaneous application these approaches may strengthen contraceptive services in Sub Saharan Africa and ensure sustainability of the efforts. The lessons learned may be used to scale up and expand services in other countries.

  10. Microdiffraction and CBED crystal structure determination of the Si-rich phase in laser-clad Ni alloy FP-5

    International Nuclear Information System (INIS)

    Liu, Y.; Mazumder, J.

    1995-01-01

    This paper demonstrates an example of using kinematical microdiffraction to solve an unknown Si-rich phase of micrometer size in a laser-clad Ni alloy FP-5 on Al alloy AA333. The composition of the Si-rich phase obtained by energy-dispersice X-ray spectroscopy (EDX) analysis in a transmission electron microscope is approximately 0.7wt%Al, 71wt%Si, 3.3wt%Cr, 0.8wt%Fe, 21wt%Ni and 2.8wt%Cu. The point group was identified by the standard convergent-beam symmetry analysis to be P6 3 /mmc (No. 194). Structure analysies by microdiffraction (MD) indicates that the Si-rich phase is a close-packed structure.The intensity distribution in the microdiffraction pattern of the [1120] zone axis taken with a very thin area showed a close match with kinematical calculation. A close-packed-structure model specified as ABCACB was deduced from the [1120] zone axis MD pattern. The randomly distributed atoms of all the elements in the unit cell are at 2/3, 1/3-1/12; 1/3, 1/12; 0, 0, 3/12, 1/3, 2/3, 5/12, 2/3, 1/3, 7/12; 0,0, 9/12. The model was checked by comparison with a simulated diffraction pattern map and with a simulated [0001] zone-axis CBED pattern, which showed complete agreement with the proposed model. (orig.)

  11. The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1

    DEFF Research Database (Denmark)

    Morland, Cecilie; Lauritzen, Knut Huso; Puchades, Maja

    2015-01-01

    We have proposed that lactate is a “volume transmitter” in the brain and underpinned this by showing that the lactate receptor, G-protein-coupled receptor 81 (GPR81, also known as HCA1 or HCAR1), which promotes lipid storage in adipocytes, is also active in the mammalian brain. This includes......, energy metabolism, and energy substrate availability, including a glucose- and glycogen-saving response. HCAR1 may contribute to optimizing the cAMP concentration. For instance, in the prefrontal cortex, excessively high cAMP levels are implicated in impaired cognition in old age, fatigue, stress...

  12. Adenosine receptor desensitization and trafficking.

    Science.gov (United States)

    Mundell, Stuart; Kelly, Eamonn

    2011-05-01

    As with the majority of G-protein-coupled receptors, all four of the adenosine receptor subtypes are known to undergo agonist-induced regulation in the form of desensitization and trafficking. These processes can limit the ability of adenosine receptors to couple to intracellular signalling pathways and thus reduce the ability of adenosine receptor agonists as well as endogenous adenosine to produce cellular responses. In addition, since adenosine receptors couple to multiple signalling pathways, these pathways may desensitize differentially, while the desensitization of one pathway could even trigger signalling via another. Thus, the overall picture of adenosine receptor regulation can be complex. For all adenosine receptor subtypes, there is evidence to implicate arrestins in agonist-induced desensitization and trafficking, but there is also evidence for other possible forms of regulation, including second messenger-dependent kinase regulation, heterologous effects involving G proteins, and the involvement of non-clathrin trafficking pathways such as caveolae. In this review, the evidence implicating these mechanisms is summarized for each adenosine receptor subtype, and we also discuss those issues of adenosine receptor regulation that remain to be resolved as well as likely directions for future research in this field. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Comparison of two neural network classifiers in the differential diagnosis of essential tremor and Parkinson's disease by {sup 123}I-FP-CIT brain SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Palumbo, Barbara [University of Perugia, Nuclear Medicine Section, Department of Surgical, Radiological and Odontostomatological Sciences, Ospedale S. Maria della Misericordia, Perugia (Italy); Fravolini, Mario Luca [University of Perugia, Department of Electronic and Information Engineering, Perugia (Italy); Nuvoli, Susanna; Spanu, Angela; Madeddu, Giuseppe [University of Sassari, Department of Nuclear Medicine, Sassari (Italy); Paulus, Kai Stephan [University of Sassari, Department of Neurology, Sassari (Italy); Schillaci, Orazio [University Tor Vergata, Department of Biopathology and Diagnostic Imaging, Rome (Italy); IRCSS Neuromed, Pozzilli (Italy)

    2010-11-15

    To contribute to the differentiation of Parkinson's disease (PD) and essential tremor (ET), we compared two different artificial neural network classifiers using {sup 123}I-FP-CIT SPECT data, a probabilistic neural network (PNN) and a classification tree (ClT). {sup 123}I-FP-CIT brain SPECT with semiquantitative analysis was performed in 216 patients: 89 with ET, 64 with PD with a Hoehn and Yahr (H and Y) score of {<=}2 (early PD), and 63 with PD with a H and Y score of {>=}2.5 (advanced PD). For each of the 1,000 experiments carried out, 108 patients were randomly selected as the PNN training set, while the remaining 108 validated the trained PNN, and the percentage of the validation data correctly classified in the three groups of patients was computed. The expected performance of an ''average performance PNN'' was evaluated. In analogy, for ClT 1,000 classification trees with similar structures were generated. For PNN, the probability of correct classification in patients with early PD was 81.9{+-}8.1% (mean{+-}SD), in patients with advanced PD 78.9{+-}8.1%, and in ET patients 96.6{+-}2.6%. For ClT, the first decision rule gave a mean value for the putamen of 5.99, which resulted in a probability of correct classification of 93.5{+-}3.4%. This means that patients with putamen values >5.99 were classified as having ET, while patients with putamen values <5.99 were classified as having PD. Furthermore, if the caudate nucleus value was higher than 6.97 patients were classified as having early PD (probability 69.8{+-}5.3%), and if the value was <6.97 patients were classified as having advanced PD (probability 88.1%{+-}8.8%). These results confirm that PNN achieved valid classification results. Furthermore, ClT provided reliable cut-off values able to differentiate ET and PD of different severities. (orig.)

  14. Cocaine Disrupts Histamine H3 Receptor Modulation of Dopamine D1 Receptor Signaling: σ1-D1-H3 Receptor Complexes as Key Targets for Reducing Cocaine's Effects

    Science.gov (United States)

    Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Hoffmann, Hanne M.; Fuentes, Silvia; Rosell-Vilar, Santi; Gasperini, Paola; Rodríguez-Ruiz, Mar; Medrano, Mireia; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carme; Ferré, Sergi; Ortiz, Jordi; Canela, Enric

    2014-01-01

    The general effects of cocaine are not well understood at the molecular level. What is known is that the dopamine D1 receptor plays an important role. Here we show that a key mechanism may be cocaine's blockade of the histamine H3 receptor-mediated inhibition of D1 receptor function. This blockade requires the σ1 receptor and occurs upon cocaine binding to σ1-D1-H3 receptor complexes. The cocaine-mediated disruption leaves an uninhibited D1 receptor that activates Gs, freely recruits β-arrestin, increases p-ERK 1/2 levels, and induces cell death when over activated. Using in vitro assays with transfected cells and in ex vivo experiments using both rats acutely treated or self-administered with cocaine along with mice depleted of σ1 receptor, we show that blockade of σ1 receptor by an antagonist restores the protective H3 receptor-mediated brake on D1 receptor signaling and prevents the cell death from elevated D1 receptor signaling. These findings suggest that a combination therapy of σ1R antagonists with H3 receptor agonists could serve to reduce some effects of cocaine. PMID:24599455

  15. Receptor studies in biological psychiatry

    International Nuclear Information System (INIS)

    Fujiwara, Yutaka

    1992-01-01

    Recent advances in the pharmacological treatment of endogenous psychosis have led to the development of biological studies in psychiatry. Studies on neurotransmitter receptors were reviewed in order to apply positron-emission tomograph (PET) for biological psychiatry. The dopamine (DA) hypothesis for schizophrenia was advanced on the basis of the observed effects of neuroleptics and methamphetamine, and DA(D 2 ) receptor supersensitivity measured by PET and receptor binding in the schizophrenic brain. The clinical potencies of neuroleptics for schizophrenia were correlated with their abilities to inhibit the D 2 receptor, and not other receptors. The σ receptor was expected to be a site of antipsychotic action. However, the potency of drugs action on it was not correlated with clinical efficacy. Haloperidol binds with high affinity to the σ receptor, which may mediate acute dystonia, an extrapyramidal side effect of neuroleptics. Behavioral and neurochemical changes induced by methamphetamine treatment were studied as an animal model of schizophrenia, and both a decrease of D 2 receptor density and an increase of DA release were detected. The monoamine hypothesis for manic-depressive psychosis was advanced on the basis of the effect of reserpine, monoamine oxidase inhibitor and antidepressants. 3 H-clonidine binding sites were increased in platelet membranes of depressive patients, 3 H-imipramine binding sites were decreased. The GABA A receptor is the target site for the action of anxiolytics and antiepileptics such as benzodiazepines and barbiturates. Recent developments in molecular biology techniques have revealed the structure of receptor proteins, which are classified into two receptor families, the G-protein coupled type (D 2 ) and the ion-channel type (GABA A ). (J.P.N.)

  16. Arrestin scaffolds NHERF1 to the P2Y12 receptor to regulate receptor internalization.

    Science.gov (United States)

    Nisar, Shaista P; Cunningham, Margaret; Saxena, Kunal; Pope, Robert J; Kelly, Eamonn; Mundell, Stuart J

    2012-07-13

    We have recently shown in a patient with mild bleeding that the PDZ-binding motif of the platelet G protein-coupled P2Y(12) receptor (P2Y(12)R) is required for effective receptor traffic in human platelets. In this study we show for the first time that the PDZ motif-binding protein NHERF1 exerts a major role in potentiating G protein-coupled receptor (GPCR) internalization. NHERF1 interacts with the C-tail of the P2Y(12)R and unlike many other GPCRs, NHERF1 interaction is required for effective P2Y(12)R internalization. In vitro and prior to agonist stimulation P2Y(12)R/NHERF1 interaction requires the intact PDZ binding motif of this receptor. Interestingly on receptor stimulation NHERF1 no longer interacts directly with the receptor but instead binds to the receptor via the endocytic scaffolding protein arrestin. These findings suggest a novel model by which arrestin can serve as an adaptor to promote NHERF1 interaction with a GPCR to facilitate effective NHERF1-dependent receptor internalization.

  17. A candidate pheromone receptor and two odorant receptors of the hawkmoth Manduca sexta.

    Science.gov (United States)

    Patch, Harland M; Velarde, Rodrigo A; Walden, Kimberly K O; Robertson, Hugh M

    2009-05-01

    In this study, we cloned and characterized three Manduca sexta odorant receptors (ORs). One receptor is a putative pheromone receptor expressed exclusively in a cell associated with male-specific type-I trichoid sensilla. We describe the results of real-time PCR (RT-PCR) and quantitative real-time PCR (qRT-PCR) experiments that show MsextaOR1 is expressed only in male antennae. In situ hybridization labels a single cell associated with type-1 trichoid sensilla, which houses two neurons that have been previously determined to respond to the major components of the pheromone blend. The second receptor, MsextaOR2, was discovered using degenerate primers designed to conserved motifs of a unique group ORs that share as much as 88% identity. Comparison of RT-PCR, qRT-PCR, and in situ hybridization results with those of ORs in the Drosophila melanogaster Or83b subfamily shows a strong sequence and expression pattern similarity. The third receptor, MsextaOR3, was found by 5'-end sequencing of a normalized and subtracted cDNA library from male M. sexta antennae. RT-PCR and qRT-PCR show that this receptor is expressed only in male and female antennae. These are the first ORs, including a putative pheromone receptor, to be described from M. sexta.

  18. Transcriptional targets shared by estrogen receptor- related receptors (ERRs) and estrogen receptor (ER) alpha, but not by ERbeta.

    Science.gov (United States)

    Vanacker, J M; Pettersson, K; Gustafsson, J A; Laudet, V

    1999-01-01

    The physiological activities of estrogens are thought to be mediated by specific nuclear receptors, ERalpha and ERbeta. However, certain tissues, such as the bone, that are highly responsive to estrogens only express a low level of these receptors. Starting from this apparent contradiction, we have evaluated the potentials of two related receptors ERRalpha and ERRbeta to intervene in estrogen signaling. ERalpha, ERRalpha and ERRbeta bind to and activate transcription through both the classical estrogen response element (ERE) and the SF-1 response element (SFRE). In contrast, ERbeta DNA-binding and transcriptional activity is restricted to the ERE. Accordingly, the osteopontin gene promoter is stimulated through SFRE sequences, by ERRalpha as well as by ERalpha, but not by ERbeta. Analysis of the cross-talk within the ER/ERR subgroup of nuclear receptors thus revealed common targets but also functional differences between the two ERs. PMID:10428965

  19. Flavivirus Entry Receptors: An Update

    Directory of Open Access Journals (Sweden)

    Manuel Perera-Lecoin

    2013-12-01

    Full Text Available Flaviviruses enter host cells by endocytosis initiated when the virus particles interact with cell surface receptors. The current model suggests that flaviviruses use at least two different sets of molecules for infectious entry: attachment factors that concentrate and/or recruit viruses on the cell surface and primary receptor(s that bind to virions and direct them to the endocytic pathway. Here, we present the currently available knowledge regarding the flavivirus receptors described so far with specific attention to C-type lectin receptors and the phosphatidylserine receptors, T-cell immunoglobulin and mucin domain (TIM and TYRO3, AXL and MER (TAM. Their role in flavivirus attachment and entry as well as their implication in the virus biology will be discussed in depth.

  20. Pharmacological characterization of receptor-activity-modifying proteins (RAMPs) and the human calcitonin receptor.

    Science.gov (United States)

    Armour, S L; Foord, S; Kenakin, T; Chen, W J

    1999-12-01

    Receptor-activity-modifying proteins (RAMPs) are a family of single transmembrane domain proteins shown to be important for the transport and ligand specificity of the calcitonin gene-related peptide (CGRP) receptor. In this report, we describe the analysis of pharmacological properties of the human calcitonin receptor (hCTR) coexpressed with different RAMPs with the use of the Xenopus laevis melanophore expression system. We show that coexpression of RAMP3 with human calcitonin receptor changed the relative potency of hCTR to human calcitonin (hCAL) and rat amylin. RAMP1 and RAMP2, in contrast, had little effect on the change of hCTR potency to hCAL or rat amylin. When coexpressed with RAMP3, hCTR reversed the relative potency by a 3.5-fold loss in sensitivity to hCAL and a 19-fold increase in sensitivity to rat amylin. AC66, an inverse agonist, produced apparent simple competitive antagonism of hCAL and rat amylin, as indicated by linear Schild regressions. The potency of AC66 was changed in the blockade of rat amylin but not hCAL responses with RAMP3 coexpression. The mean pK(B) for AC66 to hCAL was 9.4 +/- 0.3 without RAMP3 and 9.45 +/- 0.07 with RAMP3. For the antagonism of AC66 to rat amylin, the pK(B) was 9.25 +/- 0.15 without RAMP3 and 8.2 +/- 0.35 with RAMP3. The finding suggests that RAMP3 might modify the active states of calcitonin receptor in such a way as to create a new receptor phenotype that is "amylin-like." Irrespective of the physiological association of the new receptor species, the finding that a coexpressed membrane protein can completely change agonist and antagonist affinities for a receptor raises implications for screening in recombinant receptor systems.

  1. Serotonin 5-HT4 receptors and forebrain cholinergic system: receptor expression in identified cell populations.

    Science.gov (United States)

    Peñas-Cazorla, Raúl; Vilaró, M Teresa

    2015-11-01

    Activation of serotonin 5-HT4 receptors has pro-cognitive effects on memory performance. The proposed underlying neurochemical mechanism is the enhancement of acetylcholine release in frontal cortex and hippocampus elicited by 5-HT4 agonists. Although 5-HT4 receptors are present in brain areas related to cognition, e.g., hippocampus and cortex, the cellular localization of the receptors that might modulate acetylcholine release is unknown at present. We have analyzed, using dual label in situ hybridization, the cellular localization of 5-HT4 receptor mRNA in identified neuronal populations of the rat basal forebrain, which is the source of the cholinergic innervation to cortex and hippocampus. 5-HT4 receptor mRNA was visualized with isotopically labeled oligonucleotide probes, whereas cholinergic, glutamatergic, GABAergic and parvalbumin-synthesizing neurons were identified with digoxigenin-labeled oligonucleotide probes. 5-HT4 receptor mRNA was not detected in the basal forebrain cholinergic cell population. In contrast, basal forebrain GABAergic, parvalbumin synthesizing, and glutamatergic cells contained 5-HT4 receptor mRNA. Hippocampal and cortical glutamatergic neurons also express this receptor. These results indicate that 5-HT4 receptors are not synthesized by cholinergic cells, and thus would be absent from cholinergic terminals. In contrast, several non-cholinergic cell populations within the basal forebrain and its target hippocampal and cortical areas express these receptors and are thus likely to mediate the enhancement of acetylcholine release elicited by 5-HT4 agonists.

  2. Stargazin Modulation of AMPA Receptors

    Directory of Open Access Journals (Sweden)

    Sana A. Shaikh

    2016-10-01

    Full Text Available Fast excitatory synaptic signaling in the mammalian brain is mediated by AMPA-type ionotropic glutamate receptors. In neurons, AMPA receptors co-assemble with auxiliary proteins, such as stargazin, which can markedly alter receptor trafficking and gating. Here, we used luminescence resonance energy transfer measurements to map distances between the full-length, functional AMPA receptor and stargazin expressed in HEK293 cells and to determine the ensemble structural changes in the receptor due to stargazin. In addition, we used single-molecule fluorescence resonance energy transfer to study the structural and conformational distribution of the receptor and how this distribution is affected by stargazin. Our nanopositioning data place stargazin below the AMPA receptor ligand-binding domain, where it is well poised to act as a scaffold to facilitate the long-range conformational selection observations seen in single-molecule experiments. These data support a model of stargazin acting to stabilize or select conformational states that favor activation.

  3. Photo-antagonism of the GABAA receptor.

    Science.gov (United States)

    Mortensen, Martin; Iqbal, Favaad; Pandurangan, Arun P; Hannan, Saad; Huckvale, Rosemary; Topf, Maya; Baker, James R; Smart, Trevor G

    2014-07-29

    Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation.

  4. Scavenger receptors in homeostasis and immunity.

    Science.gov (United States)

    Canton, Johnathan; Neculai, Dante; Grinstein, Sergio

    2013-09-01

    Scavenger receptors were originally identified by their ability to recognize and to remove modified lipoproteins; however, it is now appreciated that they carry out a striking range of functions, including pathogen clearance, lipid transport, the transport of cargo within the cell and even functioning as taste receptors. The large repertoire of ligands recognized by scavenger receptors and their broad range of functions are not only due to the wide range of receptors that constitute this family but also to their ability to partner with various co-receptors. The ability of individual scavenger receptors to associate with different co-receptors makes their responsiveness extremely versatile. This Review highlights recent insights into the structural features that determine the function of scavenger receptors and the emerging role that these receptors have in immune responses, notably in macrophage polarization and in the pathogenesis of diseases such as atherosclerosis and Alzheimer's disease.

  5. Central alpha2 adrenergic receptors in the rat cerebral cortex: repopulation kinetics and receptor reserve

    International Nuclear Information System (INIS)

    Adler, C.H.

    1986-01-01

    The alpha 2 adrenergic receptor subtype is thought to play a role in the mechanism of action of antidepressant and antihypertensive drugs. This thesis has attempted to shed light on the regulation of central alpha 2 adrenergic receptors in the rat cerebral cortex. Repopulation kinetics analysis allows for the determination of the rate of receptor production, rate constant of degradation, and half-life of the receptor. This analysis was carried out using both radioligand binding and functional receptor assays at various times following the irreversible inactivation of central alpha 2 adrenergic receptors by in vivo administration of N-ethoxycarbonyl-2-ethyoxy-1,2-dihydroquinoline (EEDQ). Both alpha 2 agonist and antagonist ligand binding sites recovered with a t/sub 1/2/ equal to approximately 4 days. The function of alpha 2 adrenergic autoreceptors, which inhibit stimulation-evoked release of 3 H-norepinephrine ( 3 H-NE) and alpha 2 adrenergic heteroreceptors which inhibit stimulation-evoked release of 3 H-serotonin ( 3 H-5-HT) were assayed. The t/sub 1/2/ for recovery of maximal autoreceptor and heteroreceptor function was 2.4 days and 4.6 days, respectively. The demonstration of a receptor reserve is critical to the interpretation of past and future studies of the alpha 2 adrenergic receptor since it demonstrates that: (1) alterations in the number of alpha 2 adrenergic receptor binding sites cannot be extrapolated to the actual function of the alpha 2 adrenergic receptor; and (2) alterations in the number of alpha 2 receptors is not necessarily accompanied by a change in the maximum function being studied, but may only result in shifting of the dose-response curve

  6. Identifying the receptor subtype selectivity of retinoid X and retinoic acid receptors via quantum mechanics.

    Science.gov (United States)

    Tsuji, Motonori; Shudo, Koichi; Kagechika, Hiroyuki

    2017-03-01

    Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand-binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands.

  7. Interaction of epidermal growth factor receptors with the cytoskeleton is related to receptor clustering

    NARCIS (Netherlands)

    van Belzen, N.; Spaargaren, M.; Verkleij, A. J.; Boonstra, J.

    1990-01-01

    Recently it has been established that cytoskeleton-associated epidermal growth factor (EGF) receptors are predominantly of the high-affinity class and that EGF induces a recruitment of low-affinity receptors to the cytoskeleton. The nature of this EGF-induced receptor-cytoskeleton interaction,

  8. Toll-like receptors and NOD-like receptors in rheumatic diseases.

    LENUS (Irish Health Repository)

    McCormack, William J

    2012-02-01

    The past 10 years have seen the description of families of receptors that drive proinflammatory cytokine production in infection and tissue injury. Two major classes have been examined in the context of inflammatory joint disease--the Toll-like receptors (TLRs) and NOD-like receptors (NLRs). TLRs such as TLR2 and TLR4 are being implicated in the pathology of rheumatoid arthritis, ankylosing spondylitis, lyme arthritis and osteoarthritis. Nalp3 has been identified as a key NLR for IL-1beta production and has been shown to have a particular role in gout. These findings present new therapeutic opportunities, possibly allowing for the replacement of biologics with small molecule inhibitors.

  9. Olfactory Receptor Database: a sensory chemoreceptor resource

    OpenAIRE

    Skoufos, Emmanouil; Marenco, Luis; Nadkarni, Prakash M.; Miller, Perry L.; Shepherd, Gordon M.

    2000-01-01

    The Olfactory Receptor Database (ORDB) is a WWW-accessible database that has been expanded from an olfactory receptor resource to a chemoreceptor resource. It stores data on six classes of G-protein-coupled sensory chemoreceptors: (i) olfactory receptor-like proteins, (ii) vomeronasal receptors, (iii) insect olfactory receptors, (iv) worm chemoreceptors, (v) taste papilla receptors and (vi) fungal pheromone receptors. A complementary database of the ligands of these receptors (OdorDB) has bee...

  10. Molecular characterization of opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Howard, A.D.

    1986-01-01

    The aim of this research was to purify and characterize active opioid receptors and elucidate molecular aspects of opioid receptor heterogeneity. Purification to apparent homogeneity of an opioid binding protein from bovine caudate was achieved by solubilization in the non-ionic detergent, digitonin, followed by sequential chromatography on the opiate affinity matrix, ..beta..-naltrexylethylenediamine-CH-Sepharose 4B, and on the lectine affinity matrix, wheat germ agglutinin-agarose. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) followed by autoradiography revealed that radioiodinated purified receptor gave a single band. Purified receptor preparations showed a specific activity of 12,000-15,000 fmol of opiate bound per mg of protein. Radioiodinated human beta-endorphin (/sup 125/I-beta-end/sub H/) was used as a probe to investigate the ligand binding subunits of mu and delta opioid receptors. /sup 125/I-beta-end/sub H/ was shown to bind to a variety of opioid receptor-containing tissues with high affinity and specificity with preference for mu and delta sites, and with little, if any, binding to kappa sites. Affinity crosslinking techniques were employed to covalently link /sup 125/I-beta-end/sub H/ to opioid receptors, utilizing derivatives of bis-succinimidyl esters that are bifunctional crosslinkers with specificities for amino and sulfhydryl groups. This, and competition experiments with high type-selective ligands, permitted the assignment of two labeled peptides to their receptor types, namely a peptide of M/sub r/ = 65,000 for mu receptors and one of M/sub r/ = 53,000 for delta receptors.

  11. Lipid raft integrity affects GABAA receptor, but not NMDA receptor modulation by psychopharmacological compounds.

    Science.gov (United States)

    Nothdurfter, Caroline; Tanasic, Sascha; Di Benedetto, Barbara; Uhr, Manfred; Wagner, Eva-Maria; Gilling, Kate E; Parsons, Chris G; Rein, Theo; Holsboer, Florian; Rupprecht, Rainer; Rammes, Gerhard

    2013-07-01

    Lipid rafts have been shown to play an important role for G-protein mediated signal transduction and the function of ligand-gated ion channels including their modulation by psychopharmacological compounds. In this study, we investigated the functional significance of the membrane distribution of NMDA and GABAA receptor subunits in relation to the accumulation of the tricyclic antidepressant desipramine (DMI) and the benzodiazepine diazepam (Diaz). In the presence of Triton X-100, which allowed proper separation of the lipid raft marker proteins caveolin-1 and flotillin-1 from the transferrin receptor, all receptor subunits were shifted to the non-raft fractions. In contrast, under detergent-free conditions, NMDA and GABAA receptor subunits were detected both in raft and non-raft fractions. Diaz was enriched in non-raft fractions without Triton X-100 in contrast to DMI, which preferentially accumulated in lipid rafts. Impairment of lipid raft integrity by methyl-β-cyclodextrine (MβCD)-induced cholesterol depletion did not change the inhibitory effect of DMI at the NMDA receptor, whereas it enhanced the potentiating effect of Diaz at the GABAA receptor at non-saturating concentrations of GABA. These results support the hypothesis that the interaction of benzodiazepines with the GABAA receptor likely occurs outside of lipid rafts while the antidepressant DMI acts on ionotropic receptors both within and outside these membrane microdomains.

  12. Internalization of G-protein-coupled receptors: Implication in receptor function, physiology and diseases.

    Science.gov (United States)

    Calebiro, Davide; Godbole, Amod

    2018-04-01

    G protein-coupled receptors (GPCRs) are the largest family of membrane receptors and mediate the effects of numerous hormones and neurotransmitters. The nearly 1000 GPCRs encoded by the human genome regulate virtually all physiological functions and are implicated in the pathogenesis of prevalent human diseases such as thyroid disorders, hypertension or Parkinson's disease. As a result, 30-50% of all currently prescribed drugs are targeting these receptors. Once activated, GPCRs induce signals at the cell surface. This is often followed by internalization, a process that results in the transfer of receptors from the plasma membrane to membranes of the endosomal compartment. Internalization was initially thought to be mainly implicated in signal desensitization, a mechanism of adaptation to prolonged receptor stimulation. However, several unexpected functions have subsequently emerged. Most notably, accumulating evidence indicates that internalization can induce prolonged receptor signaling on intracellular membranes, which is apparently required for at least some biological effects of hormones like TSH, LH and adrenaline. These findings reveal an even stronger connection between receptor internalization and signaling than previously thought. Whereas new studies are just beginning to reveal an important physiological role for GPCR signaling after internalization and ways to exploit it for therapeutic purposes, future investigations will be required to explore its involvement in human disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. The Cannabinoid Receptor CB1 Modulates the Signaling Properties of the Lysophosphatidylinositol Receptor GPR55*

    Science.gov (United States)

    Kargl, Julia; Balenga, Nariman; Parzmair, Gerald P.; Brown, Andrew J.; Heinemann, Akos; Waldhoer, Maria

    2012-01-01

    The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid receptor 1 (CB1R) are co-expressed in many tissues, predominantly in the central nervous system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- and heteromers and initiate distinct signaling pathways. Recently, several synthetic CB1 receptor inverse agonists/antagonists, such as SR141716A, AM251, and AM281, were reported to activate GPR55. Of these, SR141716A was marketed as a promising anti-obesity drug, but was withdrawn from the market because of severe side effects. Here, we tested whether GPR55 and CB1 receptors are capable of (i) forming heteromers and (ii) whether such heteromers could exhibit novel signaling patterns. We show that GPR55 and CB1 receptors alter each others signaling properties in human embryonic kidney (HEK293) cells. We demonstrate that the co-expression of FLAG-CB1 receptors in cells stably expressing HA-GPR55 specifically inhibits GPR55-mediated transcription factor activation, such as nuclear factor of activated T-cells and serum response element, as well as extracellular signal-regulated kinases (ERK1/2) activation. GPR55 and CB1 receptors can form heteromers, but the internalization of both receptors is not affected. In addition, we observe that the presence of GPR55 enhances CB1R-mediated ERK1/2 and nuclear factor of activated T-cell activation. Our data provide the first evidence that GPR55 can form heteromers with another 7TM/GPCR and that this interaction with the CB1 receptor has functional consequences in vitro. The GPR55-CB1R heteromer may play an important physiological and/or pathophysiological role in tissues endogenously co-expressing both receptors. PMID:23161546

  14. Correlation between neuromelanin-sensitive MR imaging and 123I-FP-CIT SPECT in patients with parkinsonism

    International Nuclear Information System (INIS)

    Kuya, Keita; Shinohara, Yuki; Miyoshi, Fuminori; Fujii, Shinya; Tanabe, Yoshio; Ogawa, Toshihide

    2016-01-01

    Neuromelanin-sensitive MR imaging (MRI) can visualize neuromelanin-containing neurons in the substantia nigra pars compacta (SNc), and its utility has been reported in the evaluation of parkinsonism. Conversely, dopamine transporter imaging by 123 I-N-v-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl)nortropane (FP-CIT) SPECT (DaTSCAN) is now an established method for evaluating parkinsonism, detecting presynaptic dopamine neuronal dysfunction. Both methods can assist differentiating neurodegenerative and other forms of parkinsonism. However, to our knowledge, there have been no studies concerning a correlation between the two methods. The aim of this study was to assess the utility of neuromelanin-sensitive MRI for diagnosing parkinsonism by examining a correlation with DaTSCAN. Twenty-three patients with parkinsonism who underwent both neuromelanin-sensitive MRI and DaTSCAN were included. We measured the neuromelanin-positive SNc region volume by manually contouring the high signal intensity region of the SNc on neuromelanin-sensitive MRI and measured the specific binding ratio (SBR) on DaTSCAN. The asymmetry index of neuromelanin-positive SNc volume and the asymmetry index of SBR were also calculated. The volume of the neuromelanin-positive SNc region showed significant correlation with specific binding ratio (SBR) (right P <.001, ρ = 0.78, left P <.001, ρ = 0.86). The asymmetry index of neuromelanin-positive SNc volume also showed significant correlations with the asymmetry index of SBR (P <.001, ρ = 0.73). Decrease of the high signal intensity region of the SNc on neuromelanin-sensitive MRI would indicate damage to the nigrostriatal dopaminergic function as well as loss of dopaminergic neurons. We conclude that neuromelanin-sensitive MRI is a useful diagnostic biomarker for parkinsonism. (orig.)

  15. SN 2016coi/ASASSN-16fp: An example of residual helium in a type Ic supernova?

    Science.gov (United States)

    Prentice, S. J.; Ashall, C.; Mazzali, P. A.; Zhang, J.-J.; James, P. A.; Wang, X.-F.; Vinkó, J.; Percival, S.; Short, L.; Piascik, A.; Huang, F.; Mo, J.; Rui, L.-M.; Wang, J.-G.; Xiang, D.-F.; Xin, Y.-X.; Yi, W.-M.; Yu, X.-G.; Zhai, Q.; Zhang, T.-M.; Hosseinzadeh, G.; Howell, D. A.; McCully, C.; Valenti, S.; Cseh, B.; Hanyecz, O.; Kriskovics, L.; Pál, A.; Sárneczky, K.; Sódor, Á.; Szakáts, R.; Székely, P.; Varga-Verebélyi, E.; Vida, K.; Bradac, M.; Reichart, D. E.; Sand, D.; Tartaglia, L.

    2018-05-01

    The optical observations of Ic-4 supernova (SN) 2016coi/ASASSN-16fp, from ˜2 to ˜450 days after explosion, are presented along with analysis of its physical properties. The SN shows the broad lines associated with SNe Ic-3/4 but with a key difference. The early spectra display a strong absorption feature at ˜5400 Åwhich is not seen in other SNe Ic-3/4 at this epoch. This feature has been attributed to HeIin the literature. Spectral modelling of the SN in the early photospheric phase suggests the presence of residual He in a C/O dominated shell. However, the behaviour of the HeIlines is unusual when compared with He-rich SNe, showing relatively low velocities and weakening rather than strengthening over time. The SN is found to rise to peak ˜16 d after core-collapse reaching a bolometric luminosity of Lp ˜ 3 × 1042 erg s-1. Spectral models, including the nebular epoch, show that the SN ejected 2.5 - 4 M⊙of material, with ˜1.5 M⊙below 5000 km s-1, and with a kinetic energy of (4.5 - 7) × 1051 erg. The explosion synthesised ˜0.14 M⊙of 56Ni. There are significant uncertainties in E(B - V)host and the distance however, which will affect Lp and MNi. SN 2016coi exploded in a host similar to the Large Magellanic Cloud (LMC) and away from star-forming regions. The properties of the SN and the host-galaxy suggest that the progenitor had MZAMS of 23 - 28 M⊙and was stripped almost entirely down to its C/O core at explosion.

  16. Mechanism of A2 adenosine receptor activation. I. Blockade of A2 adenosine receptors by photoaffinity labeling

    International Nuclear Information System (INIS)

    Lohse, M.J.; Klotz, K.N.; Schwabe, U.

    1991-01-01

    It has previously been shown that covalent incorporation of the photoreactive adenosine derivative (R)-2-azido-N6-p-hydroxy-phenylisopropyladenosine [(R)-AHPIA] into the A1 adenosine receptor of intact fat cells leads to a persistent activation of this receptor, resulting in a reduction of cellular cAMP levels. In contrast, covalent incorporation of (R)-AHPIA into human platelet membranes, which contain only stimulatory A2 adenosine receptors, reduces adenylate cyclase stimulation via these receptors. This effect of (R)-AHPIA is specific for the A2 receptor and can be prevented by the adenosine receptor antagonist theophylline. Binding studies indicate that up to 90% of A2 receptors can be blocked by photoincorporation of (R)-AHPIA. However, the remaining 10-20% of A2 receptors are sufficient to mediate an adenylate cyclase stimulation of up to 50% of the control value. Similarly, the activation via these 10-20% of receptors occurs with a half-life that is only 2 times longer than that in control membranes. This indicates the presence of a receptor reserve, with respect to both the extent and the rate of adenylate cyclase stimulation. These observations require a modification of the models of receptor-adenylate cyclase coupling

  17. The First Fifteen Years of Steroid Receptor Research in Zebrafish; Characterization and Functional Analysis of the Receptors

    Directory of Open Access Journals (Sweden)

    Marcel J. M. Schaaf

    2017-07-01

    Full Text Available Steroid hormones regulate a wide range of processes in our body, and their effects are mediated by steroid receptors. In addition to their physiological role, these receptors mediate the effects of endocrine disrupting chemicals (EDCs and are widely used targets for dugs involved in the treatment of numerous diseases, ranging from cancer to inflammatory disorders. Over the last fifteen years, the zebrafish has increasingly been used as an animal model in steroid receptor research. Orthologues of all human steroid receptor genes appear to be present in zebrafish. All zebrafish steroid receptors have been characterized in detail, and their expression patterns have been analyzed. Functional studies have been performed using morpholino knockdown of receptor expression and zebrafish lines carrying mutations in one of their steroid receptor genes. To investigate the activity of the receptors in vivo, specific zebrafish reporter lines have been developed, and transcriptomic studies have been carried out to identify biomarkers for steroid receptor action. In this review, an overview of research on steroid receptors in zebrafish is presented, and it is concluded that further exploitation of the possibilities of the zebrafish model system will contribute significantly to the advancement of steroid receptor research in the next decade.

  18. How calcium makes endocytic receptors attractive

    DEFF Research Database (Denmark)

    Andersen, Christian B F; Moestrup, Søren K

    2014-01-01

    of the receptor. Endosomal acidification and calcium efflux lead to the essential ligand-receptor affinity switch and separation. Recent data, including crystal structures of receptor-ligand complexes, now reveal how calcium, in different types of domain scaffolds, functions in a common way as a removable...... 'lynchpin' that stabilizes favorable positioning of ligand-attractive receptor residues. In addition to explaining how calcium depletion can cause ligand-receptor dissociation, the new data add further insight into how acidification contributes to dissociation through structural changes that affect...... the receptor calcium sites....

  19. Pulmonary oxidative stress is increased in cyclooxygenase-2 knockdown mice with mild pulmonary hypertension induced by monocrotaline.

    Directory of Open Access Journals (Sweden)

    Francesca Seta

    Full Text Available The aim of this study was to examine the role of cyclooxygenase-2 (COX-2 and downstream signaling of prostanoids in the pathogenesis of pulmonary hypertension (PH using mice with genetically manipulated COX-2 expression. COX-2 knockdown (KD mice, characterized by 80-90% suppression of COX-2, and wild-type (WT control mice were treated weekly with monocrotaline (MCT over 10 weeks. Mice were examined for cardiac hypertrophy/function and right ventricular pressure. Lung histopathological analysis was performed and various assays were carried out to examine oxidative stress, as well as gene, protein, cytokine and prostanoid expression. We found that MCT increased right ventricular systolic and pulmonary arterial pressures in comparison to saline-treated mice, with no evidence of cardiac remodeling. Gene expression of endothelin receptor A and thromboxane synthesis, regulators of vasoconstriction, were increased in MCT-treated lungs. Bronchoalveolar lavage fluid and lung sections demonstrated mild inflammation and perivascular edema but activation of inflammatory cells was not predominant under the experimental conditions. Heme oxygenase-1 (HO-1 expression and indicators of oxidative stress in lungs were significantly increased, especially in COX-2 KD MCT-treated mice. Gene expression of NOX-4, but not NOX-2, two NADPH oxidase subunits crucial for superoxide generation, was induced by ∼4-fold in both groups of mice by MCT. Vasodilatory and anti-aggregatory prostacyclin was reduced by ∼85% only in MCT-treated COX-2 KD mice. This study suggests that increased oxidative stress-derived endothelial dysfunction, vasoconstriction and mild inflammation, exacerbated by the lack of COX-2, contribute to the pathogenesis of early stages of PH when mild hemodynamic changes are evident and not yet accompanied by vascular and cardiac remodeling.

  20. Radiosequence analysis of the human progestin receptor charged with [3H]promegestone. A comparison with the glucocorticoid receptor

    International Nuclear Information System (INIS)

    Stroemstedt, P.E.B.; Berkenstam, A.; Joernvall, H.G.; Gustafsson, J.A.; Carlstedt-Duke, J.

    1990-01-01

    Partially purified preparations of the human progestin receptor and the human and rat glucocorticoid receptor proteins were covalently charged with the synthetic progestin, [ 3 H]promegestone, by photoaffinity labeling. After labeling, the denaturated protein was cleaved and the mixture of peptides subjected to radiosequence analysis as previously described for the rat glucocorticoid receptor protein. The radioactivity labels identified, corresponded to Met-759 and Met-909 after photoaffinity labeling of the human progestin receptor, and Met-622 and Cys-754 after labeling of the rat glucocorticoid receptor. The residues labeled in the glucocorticoid receptor are the same as those previously reported to bind triamcinolone actonide. The corresponding residues were also labeled in the human glucocorticoid receptor. Met-759 of the progestin receptor and Met-622 of the rat glucocorticoid receptor are positioned within a segment with an overall high degree of sequence similarity and are equivalent. However, Met-909 (progestin receptor) and Cys-754 (glucocorticoid receptor) do not occur within equivalent segments of the two proteins. Thus, although the two classes of steroid hormone share a common structure within the A-ring, there are subtle differences in their interaction with the two separate receptor proteins

  1. Toll-like receptors in neonatal sepsis.

    LENUS (Irish Health Repository)

    O'Hare, Fiona M

    2013-06-01

    Toll-like receptors are vital transmembrane receptors that initiate the innate immune response to many micro-organisms. The discovery of these receptors has improved our understanding of host-pathogen interactions, and these receptors play an important role in the pathogenesis of multiple neonatal conditions such as sepsis and brain injury. Toll-like receptors, especially TLRs 2 and 4, are associated with necrotizing enterocolitis, periventricular leukomalacia and sepsis.

  2. Labeled receptor ligands for spect

    International Nuclear Information System (INIS)

    Kung, H.F.

    1989-01-01

    Receptor specific imaging agents for single photon emission computed tomography (SPECT) can potentially be useful in the understanding of basic biochemistry and pharmacology of receptors. SPECT images may also provide tools for evaluation of density and binding kinetics of a specific receptor, information important for diagnosis and patient management. Basic requirements for receptor imaging agents are: (a) they are labeled with short-lived isotopes, (b) they show high selectivity and specific uptake, (c) they exhibit high target/background ratio, and (d) they can be modeled to obtain quantitative information. Several good examples of CNS receptor specific ligands labeled with I-123 have been developed, including iodoQNB, iodoestrogen iodobenzadiazepine, iodobenazepine, iodobenzamides for muscarinic, estrogen benzadiazepine, D-1 and D-2 dopamine receptors. With the advent of newer and faster SPECT imaging devices, it may be feasible to quantitate the receptor density by in vivo imaging techniques. These new brain imaging agents can provide unique diagnostic information, which may not be available through other imaging modalities, such as CT and MRI

  3. The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets.

    Science.gov (United States)

    Mizejewski, G J

    2015-01-01

    Recent studies have demonstrated that the carboxyterminal third domain of alpha-fetoprotein (AFP-CD) binds with various ligands and receptors. Reports within the last decade have established that AFP-CD contains a large fragment of amino acids that interact with several different receptor types. Using computer software specifically designed to identify protein-to-protein interaction at amino acid sequence docking sites, the computer searches identified several types of scavenger-associated receptors and their amino acid sequence locations on the AFP-CD polypeptide chain. The scavenger receptors (SRs) identified were CD36, CD163, Stabilin, SSC5D, SRB1 and SREC; the SR-associated receptors included the mannose, low-density lipoprotein receptors, the asialoglycoprotein receptor, and the receptor for advanced glycation endproducts (RAGE). Interestingly, some SR interaction sites were localized on the AFP-derived Growth Inhibitory Peptide (GIP) segment at amino acids #480-500. Following the detection studies, a structural subdomain analysis of both the receptor and the AFP-CD revealed the presence of epidermal growth factor (EGF) repeats, extracellular matrix-like protein regions, amino acid-rich motifs and dimerization subdomains. For the first time, it was reported that EGF-like sequence repeats were identified on each of the three domains of AFP. Thereafter, the localization of receptors on specific cell types were reviewed and their functions were discussed.

  4. Modulating Estrogen Receptor-related Receptor-α Activity Inhibits Cell Proliferation*

    Science.gov (United States)

    Bianco, Stéphanie; Lanvin, Olivia; Tribollet, Violaine; Macari, Claire; North, Sophie; Vanacker, Jean-Marc

    2009-01-01

    High expression of the estrogen receptor-related receptor (ERR)-α in human tumors is correlated to a poor prognosis, suggesting an involvement of the receptor in cell proliferation. In this study, we show that a synthetic compound (XCT790) that modulates the activity of ERRα reduces the proliferation of various cell lines and blocks the G1/S transition of the cell cycle in an ERRα-dependent manner. XCT790 induces, in a p53-independent manner, the expression of the cell cycle inhibitor p21waf/cip1 at the protein, mRNA, and promoter level, leading to an accumulation of hypophosphorylated Rb. Finally, XCT790 reduces cell tumorigenicity in Nude mice. PMID:19546226

  5. Functionally biased signalling properties of 7TM receptors - opportunities for drug development for the ghrelin receptor

    DEFF Research Database (Denmark)

    Sivertsen, B; Holliday, N; Madsen, A N

    2013-01-01

    UNLABELLED: The ghrelin receptor is a 7 transmembrane (7TM) receptor involved in a variety of physiological functions including growth hormone secretion, increased food intake and fat accumulation as well as modulation of reward and cognitive functions. Because of its important role in metabolism...... and energy expenditure, the ghrelin receptor has become an important therapeutic target for drug design and the development of anti-obesity compounds. However, none of the compounds developed so far have been approved for commercial use. Interestingly, the ghrelin receptor is able to signal through several...... review, we have described how ligands and mutations in the 7TM receptor may bias the receptors to favour either one G-protein over another or to promote G-protein independent signalling pathways rather than G-protein-dependent pathways. For the ghrelin receptor, both agonist and inverse agonists have...

  6. Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

    Science.gov (United States)

    Bertolino, Alessandro; Taurisano, Paolo; Pisciotta, Nicola Marco; Blasi, Giuseppe; Fazio, Leonardo; Romano, Raffaella; Gelao, Barbara; Lo Bianco, Luciana; Lozupone, Madia; Di Giorgio, Annabella; Caforio, Grazia; Sambataro, Fabio; Niccoli-Asabella, Artor; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Rubini, Giuseppe

    2010-02-22

    Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

  7. Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

    Directory of Open Access Journals (Sweden)

    Alessandro Bertolino

    2010-02-01

    Full Text Available Variation of the gene coding for D2 receptors (DRD2 has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560 predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic and D2L (mainly post-synaptic. However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known.Thirty-seven healthy subjects were genotyped for rs1076560 (G>T and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors, as well as BOLD fMRI during N-Back working memory.Subjects carrying the T allele (previously associated with reduced D2S expression had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT.Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

  8. Ionotropic crustacean olfactory receptors.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Corey

    Full Text Available The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs, the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs, as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling.

  9. Optoelectronic properties of XIn{sub 2}S{sub 4} (X = Cd, Mg) thiospinels through highly accurate all-electron FP-LAPW method coupled with modified approximations

    Energy Technology Data Exchange (ETDEWEB)

    Yousaf, Masood [Department of Physics, Ulsan National Institute of Science and Technology, Ulsan 689-798 (Korea, Republic of); Physics Department, Faculty of Science, Universiti Teknologi Malaysia, Skudai 81310, Johor (Malaysia); Dalhatu, S.A. [Physics Department, Faculty of Science, Universiti Teknologi Malaysia, Skudai 81310, Johor (Malaysia); Murtaza, G. [Department of Physics, Islamia College, Peshawar, KPK (Pakistan); Khenata, R. [Laboratoire de Physique Quantique et de Modélisation Mathématique (LPQ3M), Département de Technologie, Université de Mascara, 29000 Mascara (Algeria); Sajjad, M. [School of Electronic Engineering, Beijing University of Posts and Telecommunications, Beijing 100876 (China); Musa, A. [Physics Department, Faculty of Science, Universiti Teknologi Malaysia, Skudai 81310, Johor (Malaysia); Rahnamaye Aliabad, H.A. [Department of Physics, Hakim Sabzevari University (Iran, Islamic Republic of); Saeed, M.A., E-mail: saeed@utm.my [Physics Department, Faculty of Science, Universiti Teknologi Malaysia, Skudai 81310, Johor (Malaysia)

    2015-03-15

    Highlights: • Highly accurate all-electron FP-LAPW+lo method is used. • New physical parameters are reported, important for the fabrication of optoelectronic devices. • A comparative study that involves FP-LAPW+lo method and modified approximations. • Computed band gap values have good agreement with the experimental values. • Optoelectronic results of fundamental importance can be utilized for the fabrication of devices. - Abstract: We report the structural, electronic and optical properties of the thiospinels XIn{sub 2}S{sub 4} (X = Cd, Mg), using highly accurate all-electron full potential linearized augmented plane wave plus local orbital method. In order to calculate the exchange and correlation energies, the method is coupled with modified techniques such as GGA+U and mBJ-GGA, which yield improved results as compared to the previous studies. GGA+SOC approximation is also used for the first time on these compounds to examine the spin orbit coupling effect on the band structure. From the analysis of the structural parameters, robust character is predicted for both materials. Energy band structures profiles are fairly the same for GGA, GGA+SOC, GGA+U and mBJ-GGA, confirming the indirect and direct band gap nature of CdIn{sub 2}S{sub 4} and MgIn{sub 2}S{sub 4} materials, respectively. We report the trend of band gap results as: (mBJ-GGA) > (GGA+U) > (GGA) > (GGA+SOC). Localized regions appearing in the valence bands for CdIn{sub 2}S{sub 4} tend to split up nearly by ≈1 eV in the case of GGA+SOC. Many new physical parameters are reported that can be important for the fabrication of optoelectronic devices. Optical spectra namely, dielectric function (DF), refractive index n(ω), extinction coefficient k(ω), reflectivity R(ω), optical conductivity σ(ω), absorption coefficient α(ω) and electron loss function are discussed. Optical’s absorption edge is noted to be 1.401 and 1.782 for CdIn{sub 2}S{sub 4} and MgIn{sub 2}S{sub 4}, respectively. The

  10. Dynamics of the actin cytoskeleton mediates receptor cross talk: An emerging concept in tuning receptor signaling

    Science.gov (United States)

    Mattila, Pieta K.; Batista, Facundo D.

    2016-01-01

    Recent evidence implicates the actin cytoskeleton in the control of receptor signaling. This may be of particular importance in the context of immune receptors, such as the B cell receptor, where dysregulated signaling can result in autoimmunity and malignancy. Here, we discuss the role of the actin cytoskeleton in controlling receptor compartmentalization, dynamics, and clustering as a means to regulate receptor signaling through controlling the interactions with protein partners. We propose that the actin cytoskeleton is a point of integration for receptor cross talk through modulation of protein dynamics and clustering. We discuss the implication of this cross talk via the cytoskeleton for both ligand-induced and low-level constitutive (tonic) signaling necessary for immune cell survival. PMID:26833785

  11. DMPD: Toll-like receptor 3: a link between toll-like receptor, interferon and viruses. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15031527 Toll-like receptor 3: a link between toll-like receptor, interferon and virus... (.csml) Show Toll-like receptor 3: a link between toll-like receptor, interferon and viruses. PubmedID 1503...1527 Title Toll-like receptor 3: a link between toll-like receptor, interferon and virus

  12. Andrographolide regulates epidermal growth factor receptor and transferrin receptor trafficking in epidermoid carcinoma (A-431) cells

    Science.gov (United States)

    Tan, Y; Chiow, KH; Huang, D; Wong, SH

    2010-01-01

    Background and purpose: Andrographolide is the active component of Andrographis paniculata, a plant used in both Indian and Chinese traditional medicine, and it has been demonstrated to induce apoptosis in different cancer cell lines. However, not much is known about how it may affect the key receptors implicated in cancer. Knowledge of how andrographolide affects receptor trafficking will allow us to better understand new mechanisms by which andrographolide may cause death in cancer cells. Experimental approach: We utilized the well-characterized epidermal growth factor receptor (EGFR) and transferrin receptor (TfR) expressed in epidermoid carcinoma (A-431) cells as a model to study the effect of andrographolide on receptor trafficking. Receptor distribution, the total number of receptors and surface receptors were analysed by immunofluorescence, Western blot as well as flow-cytometry respectively. Key results: Andrographolide treatment inhibited cell growth, down-regulated EGFRs on the cell surface and affected the degradation of EGFRs and TfRs. The EGFR was internalized into the cell at an increased rate, and accumulated in a compartment that co-localizes with the lysosomal-associated membrane protein in the late endosomes. Conclusion and implications: This study sheds light on how andrographolide may affect receptor trafficking by inhibiting receptor movement from the late endosomes to lysosomes. The down-regulation of EGFR from the cell surface also indicates a new mechanism by which andrographolide may induce cancer cell death. PMID:20233216

  13. In vivo studies of opiate receptors

    International Nuclear Information System (INIS)

    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented

  14. In vivo studies of opiate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented.

  15. Differential trafficking of AMPA receptors following activation of NMDA receptors and mGluRs

    Directory of Open Access Journals (Sweden)

    Sanderson Thomas M

    2011-07-01

    Full Text Available Abstract The removal of AMPA receptors from synapses is a major component of long-term depression (LTD. How this occurs, however, is still only partially understood. To investigate the trafficking of AMPA receptors in real-time we previously tagged the GluA2 subunit of AMPA receptors with ecliptic pHluorin and studied the effects of NMDA receptor activation. In the present study we have compared the effect of NMDA receptor and group I mGluR activation, using GluA2 tagged with super ecliptic pHluorin (SEP-GluA2 expressed in cultured hippocampal neurons. Surprisingly, agonists of the two receptors, which are both able to induce chemical forms of LTD, had clearly distinct effects on AMPA receptor trafficking. In agreement with our previous work we found that transient NMDA receptor activation results in an initial decrease in surface GluA2 from extrasynaptic sites followed by a delayed reduction in GluA2 from puncta (putative synapses. In contrast, transient activation of group I mGluRs, using DHPG, led to a pronounced but more delayed decrease in GluA2 from the dendritic shafts. Surprisingly, there was no average change in the fluorescence of the puncta. Examination of fluorescence at individual puncta, however, indicated that alterations did take place, with some puncta showing an increase and others a decrease in fluorescence. The effects of DHPG were, like DHPG-induced LTD, prevented by treatment with a protein tyrosine phosphatase (PTP inhibitor. The electrophysiological correlate of the effects of DHPG in the SEP-GluA2 infected cultures was a reduction in mEPSC frequency with no change in amplitude. The implications of these findings for the initial mechanisms of expression of both NMDA receptor- and mGluR-induced LTD are discussed.

  16. Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat

    NARCIS (Netherlands)

    Gispen, W.H.; Adan, R.A.H.; Szklarczyk, A.W.; Oosterom, J.; Brakkee, J.H.; Nijenhuis, W.A.; Schaaper, W.M.; Meloen, R.H.

    1999-01-01

    Since the melanocortin MC3 and melanocortin MC4 receptors are the main melanocortin receptor subtypes expressed in rat brain, we characterized the activity and affinity of nine melanocortin receptor ligands using these receptors in vitro, as well as their activity in a well-defined

  17. Correction of PF in systems with presence of harmonics; Correccion de FP en sistemas con presencia de armonicos

    Energy Technology Data Exchange (ETDEWEB)

    IMELHIA

    2005-07-01

    This document sets an example of a typical industrial plant and everything that this implies such as: an equivalent circuit and the form in which it acts as a source of harmonic currents, the initial problem: correction of the PF, the line current of this device, the current waveform (fundamental, fundamental plus fifth harmonica, h1 + h5 + h7, h1 {yields} h13 or h1 {yields} h25), the representation of harmonics, the Fourier series, the total distortion of the harmonics (THD), the classification of the harmonics, the capacitors, the reactance, the tuned filters h5 and h7, the high tension contaminated network, the extension of the network in LT, the intensities and the reactors banks. [Spanish] Este documento nos pone un ejemplo de una planta industrial tipica y todo lo que esta implica como: un circuito equivalente y la forma en que actua como una fuente de corrientes armonicas, el problema inicial: correccion FP, la corriente de linea de este dispositivo, la forma de onda en corriente (fundamental, fundamental mas quinta armonica, h1 + h5 + h7, h1 ? h13 o h1 ? h25), la representacion de armonicas, las series de Fourier, la distorsion total de las armonicas (THD), la clasificacion de las armonicas, los capacitores, la reactancia, los filtros sintonizados h5 y h7, la red de alta tension contaminada, la extension de red en BT, las intensidades y los bancos reactores.

  18. A bioluminescence resonance energy transfer 2 (BRET2) assay for monitoring seven transmembrane receptor and insulin receptor crosstalk

    DEFF Research Database (Denmark)

    Sanni, Samra Joke; Kulahin, Nikolaj; Jorgensen, Rasmus

    2017-01-01

    The angiotensin AT1 receptor is a seven transmembrane (7TM) receptor, which mediates the regulation of blood pressure. Activation of angiotensin AT1 receptor may lead to impaired insulin signaling indicating crosstalk between angiotensin AT1 receptor and insulin receptor signaling pathways....... To elucidate the molecular mechanisms behind this crosstalk, we applied the BRET2 technique to monitor the effect of angiotensin II on the interaction between Rluc8 tagged insulin receptor and GFP2 tagged insulin receptor substrates 1, 4, 5 (IRS1, IRS4, IRS5) and Src homology 2 domain-containing protein (Shc......). We demonstrate that angiotensin II reduces the interaction between insulin receptor and IRS1 and IRS4, respectively, while the interaction with Shc is unaffected, and this effect is dependent on Gαq activation. Activation of other Gαq-coupled 7TM receptors led to a similar reduction in insulin...

  19. The repertoire of olfactory C family G protein-coupled receptors in zebrafish: candidate chemosensory receptors for amino acids

    Directory of Open Access Journals (Sweden)

    Ngai John

    2006-12-01

    Full Text Available Abstract Background Vertebrate odorant receptors comprise at least three types of G protein-coupled receptors (GPCRs: the OR, V1R, and V2R/V2R-like receptors, the latter group belonging to the C family of GPCRs. These receptor families are thought to receive chemosensory information from a wide spectrum of odorant and pheromonal cues that influence critical animal behaviors such as feeding, reproduction and other social interactions. Results Using genome database mining and other informatics approaches, we identified and characterized the repertoire of 54 intact "V2R-like" olfactory C family GPCRs in the zebrafish. Phylogenetic analysis – which also included a set of 34 C family GPCRs from fugu – places the fish olfactory receptors in three major groups, which are related to but clearly distinct from other C family GPCRs, including the calcium sensing receptor, metabotropic glutamate receptors, GABA-B receptor, T1R taste receptors, and the major group of V2R vomeronasal receptor families. Interestingly, an analysis of sequence conservation and selective pressure in the zebrafish receptors revealed the retention of a conserved sequence motif previously shown to be required for ligand binding in other amino acid receptors. Conclusion Based on our findings, we propose that the repertoire of zebrafish olfactory C family GPCRs has evolved to allow the detection and discrimination of a spectrum of amino acid and/or amino acid-based compounds, which are potent olfactory cues in fish. Furthermore, as the major groups of fish receptors and mammalian V2R receptors appear to have diverged significantly from a common ancestral gene(s, these receptors likely mediate chemosensation of different classes of chemical structures by their respective organisms.

  20. Intracellular insulin-receptor dissociation and segregation in a rat fibroblast cell line transfected with a human insulin receptor gene

    International Nuclear Information System (INIS)

    Levy, J.R.; Olefsky, J.M.

    1988-01-01

    The cellular processing of insulin and insulin receptors was studied using a rat fibroblast cell line that had been transfected with a normal human insulin receptor gene, expressing approximately 500 times the normal number of native fibroblasts insulin receptors. These cells bind and internalize insulin normally. Biochemically assays based on the selective precipitation by polyethylene glycol of intact insulin-receptor complexes but not of free intracellular insulin were developed to study the time course of intracellular insulin-receptor dissociation. Fibroblasts were incubated with radiolabeled insulin at 4 0 C, and internalization of insulin-receptor complexes was initiated by warming the cells to 37 0 C. Within 2 min, 90% of the internalized radioactivity was composed of intact insulin-receptor complexes. The dissociation of insulin from internalized insulin-receptor complexes was markedly inhibited by monensin and chloroquine. Furthermore, chloroquine markedly increased the number of cross-linkable intracellular insulin-receptor complexes, as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiography. These findings suggest that acidification of intracellular vesicles is responsible for insulin-receptor dissociation. Physical segregation of dissociated intracellular insulin from its receptor was monitored. The results are consistent with the view that segregation of insulin and receptor occurs 5-10 min after initiation of dissociation. These studies demonstrate the intracellular itinerary of insulin-receptor complexes, including internalization, dissociation of insulin from the internalized receptor within an acidified compartment, segregation of insulin from the receptor, and subsequent ligand degradation