Sample records for ng m-2 d-1

  1. Resolvin D1 and D2 Reverse Lipopolysaccharide-Induced Depression-Like Behaviors Through the mTORC1 Signaling Pathway. (United States)

    Deyama, Satoshi; Ishikawa, Yuka; Yoshikawa, Kotomi; Shimoda, Kento; Ide, Soichiro; Satoh, Masamichi; Minami, Masabumi


    Resolvin D1 and D2 are bioactive lipid mediators that are generated from docosahexaenoic acid. Although recent preclinical studies suggest that these compounds have antidepressant effects, their mechanisms of action remain unclear. We investigated mechanisms underlying the antidepressant effects of resolvin D1 and resolvin D2 in lipopolysaccharide (0.8 mg/kg, i.p.)-induced depression model mice using a tail suspension test. I.c.v. infusion of resolvin D1 (10 ng) and resolvin D2 (10 ng) produced antidepressant effects; these effects were significantly blocked by a resolvin D1 receptor antagonist WRW4 (10 µg, i.c.v.) and a resolvin D2 receptor antagonist O-1918 (10 µg, i.c.v.), respectively. The mammalian target of rapamycin complex 1 inhibitor rapamycin (10 mg/kg, i.p.) and a mitogen-activated protein kinase kinase inhibitor U0126 (5 µg, i.c.v.) significantly blocked the antidepressant effects of resolvin D1 and resolvin D2. An AMPA receptor antagonist NBQX (10 mg/kg, i.p.) and a phosphoinositide 3-kinase inhibitor LY294002 (3 µg, i.c.v.) blocked the antidepressant effects of resolvin D1 significantly, but not of resolvin D2. Bilateral infusions of resolvin D1 (0.3 ng/side) or resolvin D2 (0.3 ng/side) into the medial prefrontal cortex or dentate gyrus of the hippocampus produced antidepressant effects. These findings demonstrate that resolvin D1 and resolvin D2 produce antidepressant effects via the mammalian target of rapamycin complex 1 signaling pathway, and that the medial prefrontal cortex and dentate gyrus are important brain regions for these antidepressant effects. These compounds and their receptors may be promising targets for the development of novel rapid-acting antidepressants, like ketamine and scopolamine. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  2. One step hydrothermal synthesis of 3D CoS2@MoS2-NG for high performance supercapacitors. (United States)

    Meng, Qi; Chen, Yizhi; Zhu, Wenkun; Zhang, Ling; Yang, Xiaoyong; Duan, Tao


    A three-dimensional (3D) MoS 2 coated CoS 2 -nitrogen doped graphene (NG) (CoS 2 @MoS 2 -NG) hybrid has been synthesized by a one step hydrothermal method as supercapacitor (SC) electrode material for the first time. Such a composite consists of NG embedded with stacked CoS 2 @MoS 2 sheets. With a 3D skeleton, it prevents the agglomeration of CoS 2 @MoS 2 nanoparticles, resulting in sound conductivity, rich porous structures and a large surface area. The results indicate that CoS 2 @MoS 2 -NG has higher specific capacitance (198 F g -1 at 1 A g -1 ), better rate performance (with about 56.57% from 1 to 16 A g -1 ) and an improved cycle stability (with about 96.97% after 1000 cycles). It is an ideal candidate for SC electrode materials.

  3. Prostate health index significantly reduced unnecessary prostate biopsies in patients with PSA 2-10 ng/mL and PSA >10 ng/mL: Results from a Multicenter Study in China. (United States)

    Na, Rong; Ye, Dingwei; Qi, Jun; Liu, Fang; Helfand, Brian T; Brendler, Charles B; Conran, Carly A; Packiam, Vignesh; Gong, Jian; Wu, Yishuo; Zheng, Siqun L; Mo, Zengnan; Ding, Qiang; Sun, Yinghao; Xu, Jianfeng


    The performance of prostate health index (phi) in predicting prostate biopsy outcomes has been well established for patients with prostate-specific antigen (PSA) values between 2 and 10 ng/mL. However, the performance of phi remains unknown in patients with PSA >10 ng/mL, the vast majority in Chinese biopsy patients. We aimed to assess the ability of phi to predict prostate cancer (PCa) and high-grade disease (Gleason Score ≥7) on biopsy in a Chinese population. This is a prospective, observational, multi-center study of consecutive patients who underwent a transrectal ultrasound guided prostate biopsy at four hospitals in Shanghai, China from August 2013 to December 2014. In the cohort of 1538 patients, the detection rate of PCa was 40.2%. phi had a significantly better predictive performance for PCa than total PSA (tPSA). The areas under the receiver operating characteristic curve (AUC) were 0.90 and 0.79 for phi and tPSA, respectively, P 10 ng/mL (N = 838, 54.5%). The detection rates of PCa were 35.9% and 57.7% in patients with tPSA 10.1-20 and 20.1-50 ng/mL, respectively. The AUCs of phi (0.79 and 0.89, for these two groups, respectively) were also significantly higher than tPSA (0.57 and 0.63, respectively), both P 10 ng/mL). © 2017 Wiley Periodicals, Inc.

  4. Spatial organization of NG2 glial cells and astrocytes in rat hippocampal CA1 region. (United States)

    Xu, Guangjin; Wang, Wei; Zhou, Min


    Similar to astrocytes, NG2 glial cells are uniformly distributed in the central nervous system (CNS). However, little is known about the interspatial relationship, nor the functional interactions between these two star-shaped glial subtypes. Confocal morphometric analysis showed that NG2 immunostained cells are spatially organized as domains in rat hippocampal CA1 region and that each NG2 glial domain occupies a spatial volume of ∼178, 364 μm(3) . The processes of NG2 glia and astrocytes overlap extensively; each NG2 glial domain interlaces with the processes deriving from 5.8 ± 0.4 neighboring astrocytes, while each astrocytic domain accommodates processes stemming from 4.5 ± 0.3 abutting NG2 glia. In CA1 stratum radiatum, the cell bodies of morphologically identified glial cells often appear to make direct somatic-somata contact, termed as doublets. We used dual patch recording and postrecording NG2/GFAP double staining to determine the glial identities of these doublets. We show that among 44 doublets, 50% were NG2 glia-astrocyte pairs, while another 38.6% and 11.4% were astrocyte-astrocyte and NG2 glia-NG2 glia pairs, respectively. In dual patch recording, neither electrical coupling nor intercellular biocytin transfer was detected in astrocyte-NG2 glia or NG2 glia-NG2 glia doublets. Altogether, although NG2 glia and astrocytes are not gap junction coupled, their cell bodies and processes are interwoven extensively. The anatomical and physiological relationships revealed in this study should facilitate future studies to understand the metabolic coupling and functional communication between NG2 glia and astrocytes. Copyright © 2013 Wiley Periodicals, Inc.

  5. On-Line 1D and 2D PLOT/LC-ESI-MS Using 10 μm i.d. Poly(styrene–divinylbenzene) Porous Layer Open Tubular (PLOT) Columns For Ultrasensitive Proteomic Analysis (United States)

    Luo, Quanzhou; Yue, Guihua; Valaskovic, Gary A; Gu, Ye; Wu, Shiaw-Lin; Karger, Barry L.


    Following on our recent work, on-line one dimensional (1D) and two dimensional (2D) PLOT/LC-ESI-MS platforms using 3.2 m × 10 μm i.d. poly(styrenedivinylbenzene) (PS-DVB) porous layer open tubular (PLOT) columns have been developed to provide robust, high performance and ultrasensitive proteomic analysis. Using a PicoClear tee, the dead volume connection between a 50 μm i.d. PS-DVB monolithic microSPE column and the PLOT column was minimized. The microSPE/PLOT column assembly provided a separation performance similar to that obtained with direct injection onto the PLOT column at a mobile phase flow rate of 20 nL/min. The trace analysis potential of the platform was evaluated using an in-gel tryptic digest sample of a gel fraction (15 to 40 kDa) of a cervical cancer (SiHa) cell line. As an example of the sensitivity of the system, ∼2.5 ng of protein in 2 μL solution, an amount corresponding to 20 SiHa cells, was subjected to on-line microSPE-PLOT/LC-ESIMS/MS analysis using a linear ion trap MS. 237 peptides associated with 163 unique proteins were identified from a single analysis when using stringent criteria associated with a false positive rate less than 1% . The number of identified peptides and proteins increased to 638 and 343, respectively, as the injection amount was raised to ∼45 ng of protein, an amount corresponding to 350 SiHa cells. In comparison, only 338 peptides and 231 unique proteins were identified (false positive rate again less than 1%) from 750 ng of protein from the identical gel fraction, an amount corresponding to 6000 SiHa cells, using a typical 15 cm × 75 μm i.d. packed capillary column. The greater sensitivity, higher recovery, and higher resolving power of the PLOT column resulted in the increased number of identifications from only ∼5% of the injected sample amount. The resolving power of the microSPE/PLOT assembly was further extended by 2D chromatography via combination of the high-efficiency reversed phase PLOT column

  6. M-theory solutions invariant under D(2,1; γ) + D(2,1;γ)

    International Nuclear Information System (INIS)

    Bachas, C.; D'Hoker, E.; Estes, J.; Krym, D.


    We simplify and extend the construction of half-BPS solutions to 11-dimensional supergravity, with isometry superalgebra D(2,1;γ) + D(2,1;γ). Their space-time has the form AdS 3 x S 3 x S 3 warped over a Riemann surface Σ. It describes near-horizon geometries of M2 branes ending on, or intersecting with, M5 branes along a common string. The general solution to the BPS equations is specified by a reduced set of data (γ, h, G), where γ is the real parameter of the isometry superalgebra, and h and G are functions on Σ whose differential equations and regularity conditions depend only on the sign of γ. The magnitude of γ enters only through the map of h,G onto the supergravity fields, thereby promoting all solutions into families parametrized by vertical stroke γ vertical stroke. By analyzing the regularity conditions for the supergravity fields, we prove two general theorems: (i) that the only solution with a 2-dimensional CFT dual is AdS 3 x S 3 x S 3 x R 2 , modulo discrete identifications of the flat R 2 , and (ii) that solutions with γ 4 /Z 2 or AdS 7 ' regions; highly-curved M5-branes; and a coordinate singularity called the ''cap''. By putting these ''Lego'' pieces together we recover all known global regular solutions with the above symmetry, including the self-dual strings on M5 for γ 0, but now promoted to families parametrized by vertical stroke γ vertical stroke. We also construct exactly new regular solutions which are asymptotic to AdS 4 /Z 2 for γ 0 solutions with highly curved M5-brane regions, which are the formal continuation of the self-dual string solutions across the decompactification point at γ = 0. (Copyright copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  7. Optimal screening interval for men with low baseline prostate-specific antigen levels (≤1.0 ng/mL) in a prostate cancer screening program. (United States)

    Urata, Satoko; Kitagawa, Yasuhide; Matsuyama, Satoko; Naito, Renato; Yasuda, Kenji; Mizokami, Atsushi; Namiki, Mikio


    To optimize the rescreening schedule for men with low baseline prostate-specific antigen (PSA) levels, we evaluated men with baseline PSA levels of ≤1.0 ng/mL in PSA-based population screening. We enrolled 8086 men aged 55-69 years with baseline PSA levels of ≤1.0 ng/mL, who were screened annually. The relationships of baseline PSA and age with the cumulative risks and clinicopathological features of screening-detected cancer were investigated. Among the 8086 participants, 28 (0.35 %) and 18 (0.22 %) were diagnosed with prostate cancer and cancer with a Gleason score (GS) of ≥7 during the observation period, respectively. The cumulative probabilities of prostate cancer at 12 years were 0.42, 1.0, 3.4, and 4.3 % in men with baseline PSA levels of 0.0-0.4, 0.5-0.6, 0.7-0.8, and 0.9-1.0 ng/mL, respectively. Those with GS of ≥7 had cumulative probabilities of 0.42, 0.73, 2.8, and 1.9 %, respectively. The cumulative probabilities of prostate cancer were significantly lower when baseline PSA levels were 0.0-0.6 ng/mL compared with 0.7-1.0 ng/mL. Prostate cancer with a GS of ≥7 was not detected during the first 10 years of screening when baseline PSA levels were 0.0-0.6 ng/mL and was not detected during the first 2 years when baseline PSA levels were 0.7-1.0 ng/mL. Our study demonstrated that men with baseline PSA levels of 0.0-0.6 ng/mL might benefit from longer screening intervals than those recommended in the guidelines of the Japanese Urological Association. Further investigation is needed to confirm the optimal screening interval for men with low baseline PSA levels.

  8. Chemical disease-free survival in localized carcinoma of prostate treated with external beam irradiation: comparison of American Society of Therapeutic Radiology and Oncology Consensus or 1 ng/mL as endpoint

    International Nuclear Information System (INIS)

    Perez, Carlos A.; Michalski, Jeff M.; Lockett, Mary Ann


    Purpose: To compare postirradiation biochemical disease-free survival using the American Society of Therapeutic Radiology and Oncology (ASTRO) Consensus or elevation of postirradiation prostate-specific antigen (PSA) level beyond 1 ng/mL as an endpoint and correlate chemical failure with subsequent appearance of clinically detected local recurrence or distant metastasis. Methods and Materials: Records of 466 patients with histologically confirmed adenocarcinoma of the prostate treated with irradiation alone between January 1987 and December 1995 were analyzed; 339 patients were treated with bilateral 120 deg. arc rotation and, starting in 1992, 117 with three-dimensional conformal irradiation. Doses were 68-77 Gy in 1.8 to 2 Gy daily fractions. Minimum follow-up is 4 years (mean, 5.5 years; maximum, 9.6 years). A chemical failure was recorded using the ASTRO Consensus or when postirradiation PSA level exceeded 1 ng/mL at any time. Clinical failures were determined by rectal examination, radiographic studies, and, when clinically indicated, biopsy. Results: Six-year chemical disease-free survival rates using the ASTRO Consensus according to pretreatment PSA level for T1 tumors were: ≤4 ng/mL, 100%; 4.1-20 ng/mL, 80%; and >20 ng/mL, 50%. For T2 tumors the rates were: ≤4 ng/mL, 91%; 4.1-10 ng/mL, 81%; 10.1-20 ng/mL, 55%; 20.1-40 ng/mL, 63%; and >40 ng/mL, 46%. When postirradiation PSA levels higher than 1 ng/mL were used, the corresponding 6-year chemical disease-free survival rates for T1 tumors were 92% for pretreatment PSA levels of ≤4 ng/mL, 58-60% for levels of 4.1-20 ng/mL, and 30% for levels >20 ng/mL. For T2 tumors, the 6-year chemical disease-free survival rates were 78% in patients with pretreatment PSA levels of 4-10 ng/mL, 45% for 10.1-40 ng/mL, and 25% for >40 ng/mL. Of 167 patients with T1 tumors, 30 (18%) developed a chemical failure, 97% within 5 years from completion of radiation therapy; no patient has developed a local recurrence or distant

  9. M-theory solutions invariant under D(2,1; γ) + D(2,1;γ)

    Energy Technology Data Exchange (ETDEWEB)

    Bachas, C. [Laboratoire de Physique Theorique de l' Ecole Normale Superieure Unite mixte (UMR 8549) du CNRS et de l' ENS, Paris (France); D' Hoker, E. [Department of Physics and Astronomy, University of California, Los Angeles, CA (United States); Estes, J. [Blackett Laboratory, Imperial College, London (United Kingdom); Krym, D. [Physics Department, New York City College of Technology, The City University of New York, Brooklyn, NY (United States)


    We simplify and extend the construction of half-BPS solutions to 11-dimensional supergravity, with isometry superalgebra D(2,1;γ) + D(2,1;γ). Their space-time has the form AdS{sub 3} x S{sup 3} x S{sup 3} warped over a Riemann surface Σ. It describes near-horizon geometries of M2 branes ending on, or intersecting with, M5 branes along a common string. The general solution to the BPS equations is specified by a reduced set of data (γ, h, G), where γ is the real parameter of the isometry superalgebra, and h and G are functions on Σ whose differential equations and regularity conditions depend only on the sign of γ. The magnitude of γ enters only through the map of h,G onto the supergravity fields, thereby promoting all solutions into families parametrized by vertical stroke γ vertical stroke. By analyzing the regularity conditions for the supergravity fields, we prove two general theorems: (i) that the only solution with a 2-dimensional CFT dual is AdS{sub 3} x S{sup 3} x S{sup 3} x R {sup 2}, modulo discrete identifications of the flat R {sup 2}, and (ii) that solutions with γ < 0 cannot have more than one asymptotic higher-dimensional AdS region. We classify the allowed singularities of h and G near the boundary of Σ, and identify four local solutions: asymptotic AdS{sub 4}/Z{sub 2} or AdS{sub 7}' regions; highly-curved M5-branes; and a coordinate singularity called the ''cap''. By putting these ''Lego'' pieces together we recover all known global regular solutions with the above symmetry, including the self-dual strings on M5 for γ <0, and the Janus solution for γ > 0, but now promoted to families parametrized by vertical stroke γ vertical stroke. We also construct exactly new regular solutions which are asymptotic to AdS{sub 4}/Z{sub 2} for γ < 0, and conjecture that they are a different superconformal limit of the self-dual string. Finally, we construct exactly γ > 0 solutions with highly curved M5

  10. Neuron-NG2 Cell Synapses: Novel Functions for Regulating NG2 Cell Proliferation and Differentiation

    Directory of Open Access Journals (Sweden)

    Qian-Kun Yang


    Full Text Available NG2 cells are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes, and microglia. These cells can be identified by their NG2 proteoglycan expression. NG2 cells have a highly branched morphology, with abundant processes radiating from the cell body, and express a complex set of voltage-gated channels, AMPA/kainate, and GABA receptors. Neurons notably form classical and nonclassical synapses with NG2 cells, which have varied characteristics and functions. Neuron-NG2 cell synapses could fine-tune NG2 cell activities, including the NG2 cell cycle, differentiation, migration, and myelination, and may be a novel potential therapeutic target for NG2 cell-related diseases, such as hypoxia-ischemia injury and periventricular leukomalacia. Furthermore, neuron-NG2 cell synapses may be correlated with the plasticity of CNS in adulthood with the synaptic contacts passing onto their progenies during proliferation, and synaptic contacts decrease rapidly upon NG2 cell differentiation. In this review, we highlight the characteristics of classical and nonclassical neuron-NG2 cell synapses, the potential functions, and the fate of synaptic contacts during proliferation and differentiation, with the emphasis on the regulation of the NG2 cell cycle by neuron-NG2 cell synapses and their potential underlying mechanisms.

  11. NG2 proteoglycan increases mesangial cell proliferation and extracellular matrix production

    International Nuclear Information System (INIS)

    Xiong Jing; Wang Yang; Zhu, Zhonghua; Liu Jianshe; Wang Yumei; Zhang Chun; Hammes, Hans-Peter; Lang, Florian; Feng Yuxi


    As a membrane-spanning protein, NG2 chondroitin sulfate proteoglycan interacts with molecules on both sides of plasma membrane. The present study explored the role of NG2 in the pathogenesis of diabetic nephropathy. In the normal kidneys, NG2 was observed predominantly in glomerular mesangium, Bowman's capsule and interstitial vessels. Both mRNA and protein expression in kidneys was significantly higher in strepozotocin-induced diabetic rats than that in normal rats. In the cultured rat mesangial cell line HBZY-1, overexpression of NG2 promoted mesangial cell proliferation and extracellular matrix (ECM) production, such as type VI collagen and laminin. Furthermore, target knockdown of NG2 resulted in decreased cell proliferation and ECM formation. The observations suggest that NG2 is up-regulated in diabetic nephropathy. It actively participates in the development and progression of glomerulosclerosis by stimulating proliferation of mesangial cells and deposition of ECM

  12. Positronium formation and hydrated positron reactions in H2O, D2O, 1.74 M PPS/H2O and 1.74 M PPS/D2O solutions of Cl−, Br− and I−

    DEFF Research Database (Denmark)

    Mogensen, O. E.; Pedersen, Niels Jørgen


    Angular correlation of annihilation photons were measured for H2O, D2O, 1.74 M PPS/H2O and 1.74 M PPS/D2O solutions of Cl−, Br− and I−. The three components of the angular correlation spectra for D2O and H2O were nearly identical in shape. The positronium (Ps) yields for the H2O and D2O solutions...... before annihilation (lifetime 400 ps) was determined for the three halides in the four solvents. Simple kinetic equations (“trapping model”) with time dependent rate constant, solved analytically, could explain the [X−, e+] formation in H2O fairly well for concentrations below 0.03 M X−, if a diffusion...... controlled reaction with positron diffusion constant D = 5 × 10−5 cm2/s and reaction radius R = 1 nm were assumed. The three halides gave roughly identical [X−, e+] formation below 0.03 M X−. The difference between the four solutions could be explained partly only in terms of viscosity change for the model...

  13. Photo-dynamics of the lyophilized photo-activated adenylate cyclase NgPAC2 from the amoeboflagellate Naegleria gruberi NEG-M strain

    Energy Technology Data Exchange (ETDEWEB)

    Penzkofer, A., E-mail: [Fakultät für Physik, Universität Regensburg, Universitätsstrasse 31, D-93053 Regensburg (Germany); Tanwar, M.; Veetil, S.K.; Kateriya, S. [Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi 110021 (India); Stierl, M.; Hegemann, P. [Institut für Biologie/Experimentelle Biophysik, Humboldt Universität zu Berlin, Invalidenstrasse 42, D-10115 Berlin (Germany)


    Highlights: • Lyophilizing of NgPAC2 from Naegleria gruberi caused loss of BLUF domain activity. • Photo-induced tyrosine to flavin electron transfer in lyophilized NgPAC2. • Photo-induced Tyr–Tyr cross-linking to o,o′-dityrosine in lyophilized NgPAC2. • Photo-induced partial flavin cofactor reduction in lyophilized NgPAC2. • Two NgPAC2 conformations with fast and slow photo-induced electron transfer. - Abstract: The absorption and emission spectroscopic behavior of lyophilized photo-activated adenylate cyclase NgPAC2 from the amoeboflagellate Naegleria gruberi NEG-M strain consisting of a BLUF domain (BLUF = Blue Light sensor Using Flavin) and a cyclase homology domain was studied in the dark, during blue-light exposure and after blue-light exposure at a temperature of 4 °C. The BLUF domain photo-cycle dynamics observed for snap-frozen NgPAC2 was lost by lyophilization (no signaling state formation with flavin absorption red-shift). Instead, blue-light photo-excitation of lyophilized NgPAC2 caused sterically restricted Tyr–Tyr cross-linking (o,o′-ditysosine formation) and partial flavin cofactor reduction.

  14. Photo-dynamics of the lyophilized photo-activated adenylate cyclase NgPAC2 from the amoeboflagellate Naegleria gruberi NEG-M strain

    International Nuclear Information System (INIS)

    Penzkofer, A.; Tanwar, M.; Veetil, S.K.; Kateriya, S.; Stierl, M.; Hegemann, P.


    Highlights: • Lyophilizing of NgPAC2 from Naegleria gruberi caused loss of BLUF domain activity. • Photo-induced tyrosine to flavin electron transfer in lyophilized NgPAC2. • Photo-induced Tyr–Tyr cross-linking to o,o′-dityrosine in lyophilized NgPAC2. • Photo-induced partial flavin cofactor reduction in lyophilized NgPAC2. • Two NgPAC2 conformations with fast and slow photo-induced electron transfer. - Abstract: The absorption and emission spectroscopic behavior of lyophilized photo-activated adenylate cyclase NgPAC2 from the amoeboflagellate Naegleria gruberi NEG-M strain consisting of a BLUF domain (BLUF = Blue Light sensor Using Flavin) and a cyclase homology domain was studied in the dark, during blue-light exposure and after blue-light exposure at a temperature of 4 °C. The BLUF domain photo-cycle dynamics observed for snap-frozen NgPAC2 was lost by lyophilization (no signaling state formation with flavin absorption red-shift). Instead, blue-light photo-excitation of lyophilized NgPAC2 caused sterically restricted Tyr–Tyr cross-linking (o,o′-ditysosine formation) and partial flavin cofactor reduction

  15. ( sup 3 H)(D-PEN sup 2 , D-PEN sup 5 ) enkephalin binding to delta opioid receptors on intact neuroblastoma-glioma (NG 108-15) hybrid cells

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, R.J.; Yamamura, H.I. (Univ. of Arizona College of Medicine, Tucson (USA))


    ({sup 3}H)(D-Pen{sup 2}, D-Pen{sup 5})enkephalin binding to intact NG 108-15 cells has been measured under physiological conditions of temperature and medium. The dissociation constant, receptor density, and Hill slope values measured under these conditions are consistent with values obtained by others using membranes prepared from these cells. Kinetic analysis of the radioligand binding to these cells show biphasic association and monophasic dissociation processes suggesting the presence of different receptor affinity states for the agonist. The data show that the binding affinity of ({sup 3}H)(D-Pen{sup 2}, D-Pen{sup 5})enkephalin under physiological conditions is not substantially different to that measured in 50 mM Tris buffer using cell membrane fractions. Unlike DPDPE, the {mu} opioid agonists morphine, normorphine, PL-17, and DAMGO, have much lower affinity for the {delta} receptor measured under these conditions than is observed by studies using 50 mM Tris buffer. The results described here suggest that this assay may serve as a useful model of {delta} opioid receptor binding in vivo.

  16. Salman Rushdie: "Troonide mäng" on rämps

    Index Scriptorium Estoniae


    Oma esimest telesarja "Järgmised inimesed" kirjutav Salman Rushdie ei hinda USA telekanali HBO seriaali "Troonide mäng" (George R. R. Martini "Jää ja tule laulu" sarja esimese raamatu "Troonide mäng" teleekraniseering)

  17. "Troonide mäng" toob fantaasia usutavalt teleekraanile / Mari Rebane

    Index Scriptorium Estoniae

    Rebane, Mari


    USA telekanali HBO telesarjast "Troonide mäng", George R. R. Martini "Jää ja tule laulu" sarja esimese raamatu "Troonide mäng" teleekraniseeringust. Sarja esimene osa esilinastus USA-s 17. aprillil. Osades Sean Bean jt.

  18. High-density expression of Ca2+-permeable ASIC1a channels in NG2 glia of rat hippocampus.

    Directory of Open Access Journals (Sweden)

    Yen-Chu Lin

    Full Text Available NG2 cells, a fourth type of glial cell in the mammalian CNS, undergo reactive changes in response to a wide variety of brain insults. Recent studies have demonstrated that neuronally expressed acid-sensing ion channels (ASICs are implicated in various neurological disorders including brain ischemia and seizures. Acidosis is a common feature of acute neurological conditions. It is postulated that a drop in pH may be the link between the pathological process and activation of NG2 cells. Such postulate immediately prompts the following questions: Do NG2 cells express ASICs? If so, what are their functional properties and subunit composition? Here, using a combination of electrophysiology, Ca2+ imaging and immunocytochemistry, we present evidence to demonstrate that NG2 cells of the rat hippocampus express high density of Ca2+-permeable ASIC1a channels compared with several types of hippocampal neurons. First, nucleated patch recordings from NG2 cells revealed high density of proton-activated currents. The magnitude of proton-activated current was pH dependent, with a pH for half-maximal activation of 6.3. Second, the current-voltage relationship showed a reversal close to the equilibrium potential for Na+. Third, psalmotoxin 1, a blocker specific for the ASIC1a channel, largely inhibited proton-activated currents. Fourth, Ca2+ imaging showed that activation of proton-activated channels led to an increase of [Ca2+]i. Finally, immunocytochemistry showed co-localization of ASIC1a and NG2 proteins in the hippocampus. Thus the acid chemosensor, the ASIC1a channel, may serve for inducing membrane depolarization and Ca2+ influx, thereby playing a crucial role in the NG2 cell response to injury following ischemia.

  19. Exposure to biohazards in wood dust: bacteria, fungi, endotoxins, and (1-->3)-beta-D-glucans. (United States)

    Alwis, K U; Mandryk, J; Hocking, A D


    Personal exposure to fungi, bacteria, endotoxin, and (1-->3)-beta-D-glucan was determined at different woodworking sites--logging sites, sawmills, woodchipping sites, and joineries. Exposure levels to fungi at logging sites and sawmills were in the range of 10(3)-10(4) cfu/m3, at the woodchipping mill, 10(3)-10(5) cfu/m3, and at joineries, 10(2)-10(4) cfu/m3. Although mean endotoxin levels were lower than the suggested threshold value of 20 ng/m3, some personal exposures at sawmills and a joinery exceeded the standard. The geometric mean personal (1-->3)-beta-D-glucan exposure level at the woodchipping mill was 2.32 ng/m3, at sawmills, 1.37 ng/m3, at logging sites, 2.02 ng/m3, and at joineries, 0.43 ng/m3. Highly significant associations were found between mean personal inhalable endotoxin exposures and Gram-negative bacteria levels (p 3)-beta-D-glucan exposures and fungi levels (p = 0.0003). The prevalence of cough, phlegm, chronic bronchitis, nasal symptoms, frequent headaches, and eye and throat irritations was significantly higher among woodworkers than controls. Dose-response relationships were found between personal exposures and work-related symptoms among joinery workers and sawmill and chip mill workers.

  20. Freud-2/CC2D1B mediates dual repression of the serotonin-1A receptor gene. (United States)

    Hadjighassem, Mahmoud R; Galaraga, Kimberly; Albert, Paul R


    The serotonin-1A (5-HT1A) receptor functions as a pre-synaptic autoreceptor in serotonin neurons that regulates their activity, and is also widely expressed on non-serotonergic neurons as a post-synaptic heteroreceptor to mediate serotonin action. The 5-HT1A receptor gene is strongly repressed by a dual repressor element (DRE), which is recognized by two proteins: Freud-1/CC2D1A and another unknown protein. Here we identify mouse Freud-2/CC2D1B as the second repressor of the 5-HT1A-DRE. Freud-2 shares 50% amino acid identity with Freud-1, and contains conserved structural domains. Mouse Freud-2 bound specifically to the rat 5-HT1A-DRE adjacent to, and partially overlapping, the Freud-1 binding site. By supershift assay using nuclear extracts from L6 myoblasts, Freud-2-DRE complexes were distinguished from Freud-1-DRE complexes. Freud-2 mRNA and protein were detected throughout mouse brain and peripheral tissues. Freud-2 repressed 5-HT1A promoter-reporter constructs in a DRE-dependent manner in non-neuronal (L6) or 5-HT1A-expressing neuronal (NG108-15, RN46A) cell models. In NG108-15 cells, knockdown of Freud-2 using a specific short-interfering RNA reduced endogenous Freud-2 protein levels and decreased Freud-2 bound to the 5-HT1A-DRE as detected by chromatin immunoprecipitation assay, but increased 5-HT1A promoter activity and 5-HT1A protein levels. Taken together, these data show that Freud-2 is the second component that, with Freud-1, mediates dual repression of the 5-HT1A receptor gene at the DRE. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  1. Failure to Achieve a PSA Level ≤1 ng/mL After Neoadjuvant LHRHA Therapy Predicts for Lower Biochemical Control Rate and Overall Survival in Localized Prostate Cancer Treated With Radiotherapy

    International Nuclear Information System (INIS)

    Mitchell, Darren M.; McAleese, Jonathan; Park, Richard M.; Stewart, David P.; Stranex, Stephen; Eakin, Ruth L.; Houston, Russell F.; O'Sullivan, Joe M.


    Purpose: To investigate whether failure to suppress the prostate-specific antigen (PSA) level to ≤1 ng/mL after ≥2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy in patients scheduled to undergo external beam radiotherapy for localized prostate carcinoma is associated with reduced biochemical failure-free survival. Methods and Materials: A retrospective case note review of consecutive patients with intermediate- or high-risk localized prostate cancer treated between January 2001 and December 2002 with neoadjuvant hormonal deprivation therapy, followed by concurrent hormonal therapy and radiotherapy was performed. Patient data were divided for analysis according to whether the PSA level in Week 1 of radiotherapy was ≤1.0 ng/mL. Biochemical failure was determined using the American Society for Therapeutic Radiology and Oncology (Phoenix) definition. Results: A total of 119 patients were identified. The PSA level after neoadjuvant hormonal deprivation therapy was ≤1 ng/mL in 67 patients and >1 ng/mL in 52. At a median follow-up of 49 months, the 4-year actuarial biochemical failure-free survival rate was 84% vs. 60% (p = 0.0016) in favor of the patients with a PSA level after neoadjuvant hormonal deprivation therapy of ≤1 ng/mL. The overall survival rate was 94% vs. 77.5% (p = 0.0045), and the disease-specific survival rate at 4 years was 98.5% vs. 82.5%. Conclusions: The results of our study have shown that patients with a PSA level >1 ng/mL at the beginning of external beam radiotherapy after ≥2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy have a significantly greater rate of biochemical failure and lower survival rate compared with those with a PSA level of ≤1 ng/mL. Patients without adequate PSA suppression should be considered a higher risk group and considered for dose escalation or the use of novel treatments

  2. Wireless Device-to-Device (D2D) Links for Machine-to-Machine (M2M) Communication

    DEFF Research Database (Denmark)

    Pratas, Nuno; Popovski, Petar


    Device-to-Device (D2D) communications will play an important role in the fifth generation (5G) cellular networks, by increasing the spatial reuse of spectrum resources and enabling communication links with low latency. D2D is composed of two fundamental building blocks: proximity discovery...... and direct communication between nearby users. Another emerging trend in wireless cellular systems is Machine-to-Machine (M2M) communications, often characterized by fixed, low transmission rates. In this chapter we motivate the synergy between D2D and M2M, and present technologies that enable M2M-via-D2D...

  3. Men presenting with prostate-specific antigen (PSA) values of over 100 ng/mL. (United States)

    Ang, Mann; Rajcic, Branimir; Foreman, Darren; Moretti, Kim; O'Callaghan, Michael E


    To investigate overall survival and prostate cancer-specific mortality in men with prostate cancer presenting with a PSA level PSA level extracted from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) database. Men included were diagnosed between January 1998 and August 2013. Patients were divided into groups according to diagnostic PSA level: 500 ng/mL. Outcomes measured include overall survival and prostate cancer-specific mortality. Clinical stage, Gleason score and the presence of bony metastasis was evaluated to determine if they were prognostic factors in patients with PSA over 100 at diagnosis. Cox proportional hazards and competing risks regression were used to model overall survival and prostate cancer-specific mortality outcomes respectively. Of this cohort, 241 patients (4.2%) had a diagnostic PSA level >100 ng/mL. Patients with PSA >100 ng/mL have a significant reduction in five (29.1% vs 62.5% vs 87%) and ten-year (18.2% vs 36.7% vs 70.7%) overall survival when compared to men with diagnostic PSA 20-100 and PSA level at diagnosis. Overall survival was associated with PSA level, Gleason score and age. There was a linear increase in risk (overall survival) as PSA increased until 200 and no association thereafter. Models of overall survival and prostate cancer-specific mortality incorporating a risk stratification developed by Izumi et al. predicted overall survival but not prostate cancer-specific mortality. The use of this stratification did not improve model accuracy. Only a small number of men (4.2%) with prostate cancer present with PSA >100 ng/mL at diagnosis. Overall survival at five and ten years was significantly poorer in patients with PSA >100 ng/mL. In this cohort of men presenting with PSA >100 at diagnosis, PSA level was not associated with prostate cancer-specific mortality. Gleason score and metastases are significant prognostic factors in this group of men. © 2016 The Authors BJU International © 2016

  4. T-duality of Green-Schwarz superstrings on AdS_d×S"d×M"1"0"−"2"d

    International Nuclear Information System (INIS)

    Abbott, Michael C.; Murugan, Jeff; Penati, Silvia; Pittelli, Antonio; Sorokin, Dmitri; Sundin, Per; Tarrant, Justine; Wolf, Martin; Wulff, Linus


    We verify the self-duality of Green-Schwarz supercoset sigma models on AdS_d×S"d backgrounds (d=2,3,5) under combined bosonic and fermionic T-dualities without gauge fixing kappa symmetry. We also prove this property for superstrings on AdS_d×S"d×S"d(d=2,3) described by supercoset sigma models with the isometries governed by the exceptional Lie supergroups D(2,1;α) (d=2) and D(2,1;α)×D(2,1;α) (d=3), which requires an additional T-dualisation along one of the spheres. Then, by taking into account the contribution of non-supercoset fermionic modes (up to the second order), we provide evidence for the T-self-duality of the complete type IIA and IIB Green-Schwarz superstring theory on AdS_d×S"d×T"1"0"−"2"d (d=2,3) backgrounds with Ramond-Ramond fluxes. Finally, applying the Buscher-like rules to T-dualising supergravity fields, we prove the T-self-duality of the whole class of the AdS_d×S"d×M"1"0"−"2"d superbackgrounds with Ramond-Ramond fluxes in the context of supergravity.

  5. Magnetic ordering of quasi-1 D S=1/2 Heisenberg antiferromagnet Cu benzoate at sub-mK temperatures

    International Nuclear Information System (INIS)

    Karaki, Y.; Masutomi, R.; Kubota, M.; Ishimoto, H.; Asano, T.; Ajiro, Y.


    We have measured the AC susceptibility of quasi-1D S=1/2 Heisenberg antiferromagnet Cu benzoate at temperatures down to 0.2 mK. A sharp susceptibility peak is observed at 0.8 mK under an earth field. This fact indicates a 3D ordering of linear chains coupled by a weak magnetic interaction between chains

  6. Multipotency and therapeutic potential of NG2 cells.

    Czech Academy of Sciences Publication Activity Database

    Valný, Martin; Honsa, Pavel; Kriška, Ján; Anděrová, Miroslava


    Roč. 141, SI (2017), s. 42-55 ISSN 0006-2952 R&D Projects: GA ČR(CZ) GA17-04034S Institutional support: RVO:68378041 Keywords : NG2 cells * oligodendrocyte precursor cells (OPC) * myelin plasticity Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 4.581, year: 2016

  7. CYP2R1 polymorphisms are important modulators of circulating 25-hydroxyvitamin D levels in elderly females with vitamin insufficiency, but not of the response to vitamin D supplementation. (United States)

    Arabi, A; Khoueiry-Zgheib, N; Awada, Z; Mahfouz, R; Al-Shaar, L; Hoteit, M; Rahme, M; Baddoura, R; Halabi, G; Singh, R; El Hajj Fuleihan, G


    We studied the association between CYP2R1 genetic polymorphisms and circulating 25-hydroxyvitamin D [25(OH)D] before and after supplementation with vitamin D3 in 218 elderly. We found differences between 3 and 8 ng/ml in circulating levels at baseline in women but not in the response after 1 year of supplementation. This study evaluated the association between polymorphisms in four single nucleotide polymorphisms (SNPs) of the CYP2R1 gene and 25(OH)D levels before and 1 year after supplementation with two different doses of vitamin D3 (600 IU daily or a dose equivalent to 3750 IU daily), in a cohort of 218 (96 men and 122 women) Lebanese elderly overweight subjects. Genotyping was performed for rs12794714, rs10741657, rs1562902, and rs10766197 SNPs using real-time PCR. The 25(OH)D levels were measured by liquid chromatography tandem mass spectrometry. At baseline, the mean ± SD age was 71.0 ± 4.7 years, BMI 30.3 ± 4.6 kg/m 2 , and 25(OH)D level was 20.5 ± 7.6 ng/ml. There were significant differences in mean 25(OH)D levels between genotypes in women, but not in men. After adjustment for age, season, and BMI, the homozygous for the low frequency gene variant (HLV) of rs1562902 and rs10741657 SNPs had the highest mean 25(OH)D levels with difference of 7.6 ng/ml for rs1562902 SNP (p D levels with difference of 6 ng/ml for rs10766197 (p = 0.003) and of 4.8 ng/ml (p = 0.02) for rs12794714, compared to the HLV. CYP2R1 genetic polymorphisms explained 4.8 to 9.8 % of variability in 25(OH)D in women. After 1 year, there was no difference in the response to vitamin D3 supplementation between genotypes in either gender. This study showed a difference in 25(OH)D levels between CYP2R1 genotypes that equates a daily supplementation of 400-800 IU vitamin D, depending on genotype. It underscores possible important genetic contributions for the high prevalence of hypovitaminosis D in the Middle East.

  8. Intramuscular depot formulations of leuprolide acetate suppress testosterone levels below a 20 ng/dL threshold: a retrospective analysis of two Phase III studies

    Directory of Open Access Journals (Sweden)

    Spitz A


    Full Text Available Aaron Spitz,1 Marc Gittelman,2 Lawrence I Karsh,3 Sanja Dragnic,4 Ahmed M Soliman,5 Aditya Lele,6 Damian Gruca,7 Michael Norton4 1Orange County Urology Associates, Laguna Beach, CA, 221st Century Oncology/UroMedix-Aventura Division, Aventura, FL, 3The Urology Center of Colorado, Denver, CO, 4US Medical Affairs, 5Health Economics and Outcomes Research, 6Data and Statistical Sciences, AbbVie Inc., North Chicago, IL, USA; 7Global Medical Affairs, AbbVie Deutschland, Ludwigshafen, Germany Introduction: Androgen deprivation therapy (ADT with gonadotropin-releasing hormone (GnRH analogs is a standard treatment for advanced prostate cancer. GnRH analog therapy can reduce testosterone to “castrate” levels, historically defined as <50 ng/dL. With the advent of newer assays, a lower threshold of <20 ng/dL has recently been proposed. We report the results of a retrospective analysis of two Phase III trials of 4- and 6-month depot microsphere formulations of leuprolide acetate (LA, a GnRH agonist that has previously demonstrated efficacy in testosterone suppression to <50 ng/dL in patients on ADT. This analysis investigates the ability of these LA formulations to suppress to ≤20 ng/dL levels.Methods: In two of five AbbVie/Abbott clinical trials of microsphere formulations of LA for ADT, analytic technology permitting testosterone detection as low as 3 ng/dL was used and thus was selected for this analysis. Both trials were open-label, fixed-dose studies in prostate cancer patients, naïve to ADT. Patients received either 30 mg (4-month formulation; n=49 or 45 mg (6-month formulation; n=151 depot injections of LA microspheres. Treatment duration was up to 32 weeks for the 4-month formulation and 48 weeks for the 6-month formulation. The proportion of patients achieving the 20 ng/dL threshold was determined every 4 weeks.Results: Pooled analysis showed that 152 of 193 (79% of patients achieved serum testosterone levels of ≤20 ng/dL at 4 weeks, and

  9. Alpha-fetoprotein level > 1000 ng/mL as an exclusion criterion for liver transplantation in patients with hepatocellular carcinoma meeting the Milan criteria. (United States)

    Hameed, Bilal; Mehta, Neil; Sapisochin, Gonzalo; Roberts, John P; Yao, Francis Y


    Serum alpha-fetoprotein (AFP) has been increasingly recognized as a marker for a poor prognosis after liver transplantation (LT) for hepatocellular carcinoma (HCC). Many published reports, however, have included a large proportion of patients with HCC beyond the Milan criteria, and the effects of incorporating AFP as an exclusion criterion for LT remain unclear. We studied 211 consecutive patients undergoing LT for HCC within the Milan criteria according to imaging under the Model for End-Stage Liver Disease organ allocation system between June 2002 and January 2009. The majority (93.4%) had locoregional therapy before LT. The median follow-up was 4.5 years (minimum = 2 years). The Kaplan-Meier 1- and 5-year patient survival rates were 94.3% and 83.4%, respectively. In a univariate analysis, significant predictors of HCC recurrence included vascular invasion [hazard ratio (HR) = 10, 95% confidence interval (CI) = 3.9-26, P 1000 ng/mL (HR = 4.5, 95% CI = 1.3-15.3, P = 0.02), and an AFP level > 500 ng/mL (HR = 3.1, 95% CI = 1.04-9.4, P = 0.04). In a multivariate analysis, vascular invasion was the only significant predictor of tumor recurrence (HR = 5.6, 95% CI = 1.9-19, P = 0.02). An AFP level > 1000 ng/mL was the strongest pretransplant variable predicting vascular invasion (odds ratio = 6.8, 95% CI = 1.6-19.1, P = 0.006). The 1- and 5-year rates of survival without recurrence were 90% and 52.7%, respectively, for patients with an AFP level > 1000 ng/mL and 95% and 80.3%, respectively, for patients with an AFP level ≤ 1000 ng/mL (P = 0.026). Applying an AFP level > 1000 ng/mL as a cutoff would have resulted in the exclusion of 4.7% of the patients fr m LT and a 20% reduction in HCC recurrence. In conclusion, an AFP level > 1000 ng/mL may be a surrogate for vascular invasion and may be used to predict posttransplant HCC recurrence. Incorporating an AFP level > 1000 ng/mL as an exclusion criterion for LT within the Milan criteria may further improve posttransplant

  10. Aggregation and Trunking of M2M Traffic via D2D Connections

    DEFF Research Database (Denmark)

    Rigazzi, Giovanni; Kiilerich Pratas, Nuno; Popovski, Petar


    Machine-to-Machine (M2M) communications is one of the key enablers of the Internet of Things (IoT). Billions of devices are expected to be deployed in the near future for novel M2M applications demanding ubiquitous access and global connectivity. In order to cope with the massive number of machines......, there is a need for new techniques to coordinate the access and allocate the resources. Although the majority of the proposed solutions are focused on the adaptation of the traditional cellular networks to the M2M traffic patterns, novel approaches based on the direct communication among nearby devices may...... represent an effective way to avoid access congestion and cell overload. In this paper, we propose a new strategy inspired by the classical Trunked Radio Systems (TRS), exploiting the Device-to-Device (D2D) connectivity between cellular users and Machine-Type Devices (MTDs). The aggregation of the locally...

  11. Effect of 24,25-dihydroxyvitamin D3 on 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] metabolism in vitamin D-deficient rats infused with 1,25-(OH)2D3

    International Nuclear Information System (INIS)

    Yamato, H.; Matsumoto, T.; Fukumoto, S.; Ikeda, K.; Ishizuka, S.; Ogata, E.


    Previous studies revealed that administration of 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] to calcium (Ca)-deficient rats causes a dose-dependent reduction in markedly elevated serum 1,25-(OH)2D3 level. Although the results suggested that the metabolism of 1,25-(OH)2D3 was accelerated by 24,25-(OH)2D3, those experiments could not define whether the enhanced metabolism of 1,25-(OH)2D3 played a role in the reduction in the serum 1,25-(OH)2D3 level. In the present study, in order to address this issue more specifically, serum 1,25-(OH)2D3 was maintained solely by exogenous administration through miniosmotic pumps of 1,25-(OH)2D3 into vitamin D-deficient rats. Thus, by measuring the serum 1,25-(OH)2D3 concentration, the effect of 24,25-(OH)2D3 on the MCR of 1,25-(OH)2D3 could be examined. Administration of 24,25-(OH)2D3 caused a dose-dependent enhancement in the MCR of 1,25-(OH)2D3, and 1 microgram/100 g 24,25-(OH)2D3, which elevated serum 24,25-(OH)2D3 to 8.6 +/- 1.3 ng/ml, significantly increased MCR and suppressed serum levels of 1,25-(OH)2D3. The effect of 24,25-(OH)2D3 on 1,25-(OH)2D3 metabolism developed with a rapid time course, and the recovery of iv injected [1 beta-3H]1,25-(OH)2D3 in blood was significantly reduced within 1 h. In addition, there was an increase in radioactivity in the water-soluble fraction of serum as well as in urine, suggesting that 1,25-(OH)2D3 is rapidly degraded to a water-soluble metabolite(s). Furthermore, the reduction in serum 1,25-(OH)2D3 was associated with a reduction in both serum and urinary Ca levels. Because the conversion of [3H]24,25-(OH)2D3 to [3H]1,24,25-(OH)2D3 or other metabolites was minimal in these rats, 24,25-(OH)2D3 appears to act without being converted into other metabolites. These results demonstrate that 24,25-(OH)2D3 rapidly stimulates the metabolism of 1,25-(OH)2D3 and reduces its serum level

  12. 76 FR 27861 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG... (United States)


    ... Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG Airplanes... on Diamond aeroplanes, the majority of which were DA 40. In additional, at least 18 doors have been... conditions) while the aeroplane was parked. All DA 40 and DA 42 aeroplanes have a system installed that...

  13. Predictive value of [-2]propsa (p2psa and its derivatives for the prostate cancer detection in the 2.0 to 10.0ng/mL PSA range

    Directory of Open Access Journals (Sweden)

    I. Vukovic

    Full Text Available ABSTRACT Introduction To assess predictive value of new tumor markers, precursor of prostate specific antigen (p2PSA and its derivates-%p2PSA and prostate health index (PHI in detection of patients with indolent and aggressive prostate cancer (PC in a subcohort of man whose total PSA ranged from 2 to 10ng/mL. Materials and Methods This cross-sectional study included 129 consecutive male patients aged over 50 years, with no previous history of PC and with normal digital rectal examination findings, but with serum PSA in interval between 2 and 10ng/mL. All patients underwent standard transrectal ultrasonography guided prostate biopsy for the first time. For all patients, serum PSA, free PSA (fPSA and p2PSA were measured and PHI and %p2PSA were calculated. Results PHI and %p2PSA levels were significanlty higher in patients with PC compared to those without this malignancy. The same findings have been observed in group of patients with Gleason score ≥7 compared to those with Gleason score <7. ROC analysis reveled the highest area under the curve with these two markers. Multivariate logistic regression showed significant improvement in PC detection and its agressive form (assumed as Gleason score ≥7. Conclusions New markers, derivates of p2PSA (especially %p2PSA and PHI, represente potentially very important clinical tool for predicting presence of PC, and even more important, to discriminate patients with Gleason score <7 from those with Gleason score ≥7 with total PSA in range from 2 to 10ng/mL.

  14. Predictive value of [-2]propsa (p2psa) and its derivatives for the prostate cancer detection in the 2.0 to 10.0ng/mL PSA range. (United States)

    Vukovic, I; Djordjevic, D; Bojanic, N; Babic, U; Soldatovic, I


    To assess predictive value of new tumor markers, precursor of prostate specific antigen (p2PSA) and its derivates-%p2PSA and prostate health index (PHI) in detection of patients with indolent and aggressive prostate cancer (PC) in a subcohort of man whose total PSA ranged from 2 to 10ng/mL. This cross-sectional study included 129 consecutive male patients aged over 50 years, with no previous history of PC and with normal digital rectal examination findings, but with serum PSA in interval between 2 and 10ng/mL. All patients underwent standard transrectal ultrasonography guided prostate biopsy for the first time. For all patients, serum PSA, free PSA (fPSA) and p2PSA were measured and PHI and %p2PSA were calculated. PHI and %p2PSA levels were significanlty higher in patients with PC compared to those without this malignancy. The same findings have been observed in group of patients with Gleason score ≥7 compared to those with Gleason score <7. ROC analysis reveled the highest area under the curve with these two markers. Multivariate logistic regression showed significant improvement in PC detection and its agressive form (assumed as Gleason score ≥7). New markers, derivates of p2PSA (especially %p2PSA and PHI), represente potentially very important clinical tool for predicting presence of PC, and even more important, to discriminate patients with Gleason score <7 from those with Gleason score ≥7 with total PSA in range from 2 to 10ng/mL. Copyright® by the International Brazilian Journal of Urology.

  15. 76 FR 12627 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG... (United States)


    ... Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG Airplanes AGENCY: Federal Aviation Administration (FAA... on Diamond aeroplanes, the majority of which were DA 40. In additional, at least 18 doors have been... conditions) while the aeroplane was parked. All DA 40 and DA 42 aeroplanes have a system installed that...

  16. Geometry and bonding in the ground and lowest triplet state of D{sub 6h} symmetric crenellated edged C{sub 6[3m(m-1)+1]}H{sub 6(2m-1)} (m = 2,..., 6) graphene hydrocarbon molecules

    Energy Technology Data Exchange (ETDEWEB)

    Philpott, Michael R., E-mail: [Center for Computational Materials Science, Institute of Materials Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, 980-8577 Sendai (Japan); Kawazoe, Yoshiyuki [Center for Computational Materials Science, Institute of Materials Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, 980-8577 Sendai (Japan)


    Ab initio plane wave all valence electron based DFT calculations were used to explore the dichotomy of perimeter vs. interior in the electronic and geometric structure of the D{sub 6h} singlet ground state and D{sub 2h} lowest triplet state of planar graphene hydrocarbon molecules with crenellated (arm chair) edges and the general formula C{sub 6[3m(m-1)+1]} H{sub 6(2m-1)} where m = 2,...,6. The largest molecule C{sub 546}H{sub 66} was 4.78 nm across and contained 2250 valence electrons. These molecules are nominally 'fully benzenoid hydrocarbons'. However with increasing size, the core of central atoms abandoned any fully benzenoid geometry they had in small systems and organized into single layer graphite (graphene) structure. The perimeter atoms of the crenellation adopted a conjugated geometry with unequal bonds and between core and perimeter there were some C{sub 6} rings retaining remnants of aromatic sextet-type properties. Compared to a zigzag edge the crenellated edge conferred stability in all the systems studied as measured by the singlet homo-lumo level gap BG{sub 0} and the singlet-lowest triplet energy gap {Delta}E{sub ST}. For the largest crenellated system (m = 6) BG{sub 0} and {Delta}E{sub ST} were approximately 0.7 eV, larger in value than for similarly sized hexagonal graphenes with zigzag edges. Triplet states were identified for all the molecules in the series and in the case of the m = 2 molecule hexabenzocoronene C{sub 42}H{sub 18}, two conformations with D{sub 2h} symmetry were identified and compared to features on the triplet state potential energy surface of benzene.

  17. On relating multiple M2 and D2-branes

    International Nuclear Information System (INIS)

    Gran, U.; Nilsson, B.E.W; Petersson, C.


    Due to the difficulties of finding superconformal Lagrangian theories for multiple M2-branes, we will in this paper instead focus on the field equations. By relaxing the requirement of a Lagrangian formulation we can explore the possibility of having structure constants f ABC D satisfying the fundamental identity but which are not totally antisymmetric. We exemplify this discussion by making use of an explicit choice of a non-antisymmetric f ABC D constructed from the Lie algebra structure constants f ab c of an arbitrary gauge group. Although this choice of f ABC D does not admit an obvious Lagrangian description, it does reproduce the correct SYM theory for a stack of N D2-branes to leading order in g YM -1 upon reduction and, moreover, it sheds new light on the centre of mass coordinates for multiple M2-branes.

  18. Vitamin D deficiency in type 2 diabetic patients with hypogonadism. (United States)

    Bellastella, Giuseppe; Maiorino, Maria Ida; Olita, Laura; Capuano, Annalisa; Rafaniello, Concetta; Giugliano, Dario; Esposito, Katherine


    Both type 2 diabetes and secondary hypogonadism may be associated with low vitamin D levels. The aim of this study was to evaluate 25-hydroxyvitamin D (25(OH)D) concentrations in type 2 diabetic males with and without hypogonadism. We performed a case-control study among 122 male adults with type 2 diabetes, 51 with associated hypogonadism (Group 1) and 71 with normal gonadal function (Group 2). One hundred age-matched nondiabetic males with normal gonadal function served as a control group. Levels of 25(OH)D were assessed by a chemiluminescent immunoassay in all patients. Morning testosterone, pituitary, thyroid, parathyroid hormones, fasting glucose, and hemoglobin A1c were also evaluated. The overall diabetic population showed a mean 25(OH)D concentration (22.3 ± 6.09 ng/mL) significantly lower than the control group (34.3 ± 7.2, P hypogonadism as compared with the 9 patients with hypergonadotropic hypogonadism (19.4 ± 7.06 vs. 23.8 ± 6.11 ng/mL, P hypogonadism present lower 25(OH)D concentration and higher prevalence of vitamin D deficiency, compared with patients without hypogonadism. The finding that 25(OH)D concentrations were similar between type 2 diabetic patients with hypergonadotropic hypogonadism and those with normal gonadal function deserves further study. © 2013 International Society for Sexual Medicine.

  19. Clinical utility of serum folate measurement in tertiary care patients: Argument for revising reference range for serum folate from 3.0 ng/mL to 13.0 ng/mL

    Directory of Open Access Journals (Sweden)

    Gurmukh Singh


    Full Text Available Objective: Assess the need for folate testing, frequency of corrective action, and determine reference level for serum folate. Methods: Serum folate levels in 5313 samples from 4448 patients, and clinical data were reviewed for patient characteristics and for (a evidence of corrective action in patients with serum folate values 25.7 ng/mL. Results: The prevalence of serum folate levels, in patients, 25.7 ng/mL the sample was collected after supplementation with folic acid. Of the 128 patients with serum folate 60% of the patients. Since serum folate levels ≥13.0 ng/mL are needed for optimal prevention of neural tube defects in the embryo/fetus, we propose that normal serum folate level should be designated to be ≥13.0 ng/mL. Keywords: Serum folate, Prevalence of folate deficiency, Neural tube defects, Optimum serum folate level, Utility of folate testing

  20. Effect of 1,25(OH)2 vitamin D3 and ionized Ca2+ on 45Ca uptake by primary cultures of aortic myocytes of spontaneously hypertensive and Wistar Kyoto normotensive rats

    International Nuclear Information System (INIS)

    Bukoski, R.D.; Xue, H.; McCarron, D.A.


    The effect of several regulators of whole animal Ca 2+ homeostasis on 45 Ca uptake by primary cultures of aortic myocytes isolated from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats was examined. Exposure of confluent cells to 1.0, 1.25 or 1.50 mM ionized Ca 2+ in serum-free medium for seven days resulted in increased 45 Ca uptake at the higher concentrations of Ca 2+ in cells of the SHR but not the WKY. 1,25 (OH)2 vitamin D3 (1 ng/ml) for 7 days caused enhanced influx in cells from both the SHR and WKY while parathyroid hormone (1-34) (1 ng/ml) was without effect. The data indicate that humoral factors that serve to regulate whole animal Ca 2+ homeostasis may also play a role in the regulation of Ca 2+ metabolism of the vascular smooth muscle cell

  1. Complete Suppression of the m=2/n=1 NTM Using ECCD on DIII-D

    International Nuclear Information System (INIS)

    Petty, C.C.; La Haye, R.J.; Luce, T.C.; Humphreys, D.A.; Lohr, J.; Prater, R.; Austin, M.E.; Harvey, R.W.; Wade, M.R.


    Complete suppression of the m=2/n=1 neoclassical tearing mode (NTM) is reported for the first time using electron cyclotron current drive (ECCD) to noninductively generate current at the radius of the island O-point. Experiments on the DIII-D tokamak show that the maximum shrinkage of the m=2/n=1 island amplitude occurs when the ECCD location coincides with the q=2 surface. Estimates of the ECCD radial profile width from the island shrinkage are consistent with ray tracing calculations but may allow for a factor-of-1.5 broadening from electron radial transport

  2. Impact of PSA density of transition zone as a potential parameter in reducing the number of unnecessary prostate biopsies in patients with psa levels between 2.6 and 10.0 ng/mL. (United States)

    Castro, Hugo A Socrates; Iared, Wagner; Santos, José Eduardo Mourão; Solha, Raphael Sandes; Shigueoka, David Carlos; Ajzen, Sergio Aron


    To assess the accuracy of prostate-specific antigen (PSA) adjusted for the transition zone volume (PSATZ) in predicting prostate cancer by comparing the ability of several PSA parameters in predicting prostate cancer in men with intermediate PSA levels of 2.6 - 10.0 ng/mL and its ability to reduce unnecessary biopsies. This study included 656 patients referred for prostate biopsy who had a serum PSA of 2.6 - 10.0 ng/mL. Total prostate and transition zone volumes were measured by transrectal ultrasound using the prolate ellipsoid method. The clinical values of PSA, free-to-total (F/T) ratio, PSA density (PSAD) and PSATZ for the detection of prostate cancer were calculated and statistical comparisons between biopsy-positive (cancer) and biopsy-negative (benign) were conducted. Cancer was detected in 172 patients (26.2%). Mean PSA, PSATZ, PSAD and F/T ratio were 7.5 ng/mL, 0.68 ng/mL/cc. 0.25 ng/mL/cc and 0.14 in patients with prostate cancer and 6.29 ng/mL, 0.30 ng/mL/cc, 0.16 ng/mL/cc and 0.22 in patients with benign biopsies, respectively. ROC curves analysis demonstrated that PSATZ had a higher area under curve (0,838) than F/T ratio (0,806) (PPSA. Compared to other PSA related parameters, it was better in differentiating between prostate cancer and benign prostatic enlargement. Also, PSATZ could reduce a significant number of unnecessary biopsies. Copyright® by the International Brazilian Journal of Urology.

  3. Comparison of Transport Calculation Between 2D/1D synthesis and RAPTOR-M3G at Core Barrel of Korea Standard Nuclear Plant(KSNP), OPR-1000

    Energy Technology Data Exchange (ETDEWEB)

    Maeng, Young Jae; Kim, Byoung Chul; Lim, Mi Joung; Kim, Kyung Sik; Jeon, Young Kyou [Korea Reactor Integrity Surveillance Technology, Daejeon (Korea, Republic of); Yoo, Chun Sung [Korea Atomic Energy Research Institutes, Daejeon (Korea, Republic of)


    The DORT code for 2D/1D synthesis has been actively applied to calculate the fast neutron (E>1.0MeV) fluence exposure of RPV. RAPTOR-M3G code is also applied for the comparison of 2D/1D synthesis, and it was found that 2D/1D synthesis method generally provided more conservative results than RAPTOR-M3G at both RPV and surveillance capsule locations. As a result, definitely RAPTOR-M3G for 3D calculation must apply for accurate evaluation of the integrity and ageing of RPV and internal structures. Therefore, the purpose of this paper is to compare the differences in terms of geometric aspect of KSNP model between 2D/1D synthesis and RAPTOR-M3G at core barrel area. 2D/1D synthesis method shows still higher results at the shortest distance of bypass water region. The reason is that 2D/1D synthesis method has excessive conservatism because of having just one model of R-θ and R-Z separately. Angles (5, 25, 45, 65 and 90 degrees) that RAPTOR-M3G results are higher than 2D/1D synthesis results seem to have almost regular interval. The reason can be that neutron flux to reach to barrel is affected by the nearest core definitely and all of near core areas including bypass water. RAPTOR-M3G performing 3D calculation can be applied to various reactor structures, because the code can simulate the model realistically and reasonably in geometric view points. Understanding the phenomenon that 45 degree shows downward peak, in spite of baffle corner location, remains.

  4. Comparison of Transport Calculation Between 2D/1D synthesis and RAPTOR-M3G at Core Barrel of Korea Standard Nuclear Plant(KSNP), OPR-1000

    International Nuclear Information System (INIS)

    Maeng, Young Jae; Kim, Byoung Chul; Lim, Mi Joung; Kim, Kyung Sik; Jeon, Young Kyou; Yoo, Chun Sung


    The DORT code for 2D/1D synthesis has been actively applied to calculate the fast neutron (E>1.0MeV) fluence exposure of RPV. RAPTOR-M3G code is also applied for the comparison of 2D/1D synthesis, and it was found that 2D/1D synthesis method generally provided more conservative results than RAPTOR-M3G at both RPV and surveillance capsule locations. As a result, definitely RAPTOR-M3G for 3D calculation must apply for accurate evaluation of the integrity and ageing of RPV and internal structures. Therefore, the purpose of this paper is to compare the differences in terms of geometric aspect of KSNP model between 2D/1D synthesis and RAPTOR-M3G at core barrel area. 2D/1D synthesis method shows still higher results at the shortest distance of bypass water region. The reason is that 2D/1D synthesis method has excessive conservatism because of having just one model of R-θ and R-Z separately. Angles (5, 25, 45, 65 and 90 degrees) that RAPTOR-M3G results are higher than 2D/1D synthesis results seem to have almost regular interval. The reason can be that neutron flux to reach to barrel is affected by the nearest core definitely and all of near core areas including bypass water. RAPTOR-M3G performing 3D calculation can be applied to various reactor structures, because the code can simulate the model realistically and reasonably in geometric view points. Understanding the phenomenon that 45 degree shows downward peak, in spite of baffle corner location, remains

  5. Infrared Spectra of Novel NgBeSO2 Complexes (Ng = Ne, Ar, Kr, Xe) in Low Temperature Matrixes. (United States)

    Yu, Wenjie; Liu, Xing; Xu, Bing; Xing, Xiaopeng; Wang, Xuefeng


    The novel noble-gas complexes NgBeSO 2 (Ng = Ne, Ar, Kr, Xe) have been prepared in the laser-evaporated beryllium atom reactions with SO 2 in low-temperature matrixes. Doped with heavier noble gas, the guest (Ar, Kr, Xe) atom can substitute neon to form more stable complex. Infrared spectroscopy and theoretical calculations are used to confirm the band assignment. The dissociation energies are calculated at 0.9, 4.0, 4.7, and 6.0 kcal/mol for NeBeSO 2 , ArBeSO 2 , KrBeSO 2 , and XeBeSO 2 , respectively, at the CCSD(T) level. Quantum chemical calculations demonstrate that the Ng-Be bonds in NgBeSO 2 could be formed by the combination of electron-donation and ion-induced dipole interactions. The Wiberg bond index (WBI) values of Ng-Be bonds and LOL (localized orbital locator) profile indicate that the Ng-Be bond exhibits a gradual increase in covalent character along Ne to Xe.


    International Nuclear Information System (INIS)



    A271 COMPLETE SUPPRESSION OF THE M=2/N-1 NEOCLASSICAL TEARING MODE USING ELECTRON CYCLOTRON CURRENT DRIVE ON DIII-D. The first suppression of the important and deleterious m=2/n=1 neoclassical tearing mode (NTM) is reported using electron cyclotron current drive (ECCD) to replace the ''missing'' bootstrap current in the island O-point. Experiments on the DIII-D tokamak verify the maximum shrinkage of the m=2/n=1 island occurs when the ECCD location coincides with the q = 2 surface. The DIII-D plasma control system is put into search and suppress mode to make small changes in the toroidal field to find and lock onto the optimum position, based on real time measurements of dB θ /dt, for complete m=2/n=1 NTM suppression by ECCD. The requirements on the ECCD for complete island suppression are well modeled by the modified Rutherford equation for the DIII-D plasma conditions

  7. The development of 99mTc-d, 1-HM-PAO

    International Nuclear Information System (INIS)

    Bai Lanqin; Huang Jinjie; Fan Li; Bai Suzhen; Li Guoli; Jing Hui; Xiao Lun


    The 99m Tc-d,1-HM-PAO is an ideal radiopharmaceutical for regional cerebral blood perfusion imaging. The improvement of synthesis and separation of diastereoisomers leads to obtain high purity (>99%) of d, 1-HM-PAO and meso-HM-PAO. During separation H NMR spectroscopy was used to monitor the relative composition of these two diastereoisomers that can ensure the purity of pligand of d,1-HM-PAO. The intravenous injection of 99m Tc-d,1-HM-PAO was formed by adding fresh 99m Tc washing liquor into a sterile. Pyrogen-free and freeze-dried vial. The radiochemical purity (RCP) of 99m Tc-d,1-HM-PAO was greater than 80%. From the experiments of 99m Tc-d,1-HM-PAO in mice, after two minutes of intravenously (I>V>) administration about 2.24% of injected dose (I.D.)appeared in the brain, and after 24 hours about 72% of radioactivity of injected dose still left in the brain. But for the 99m Tc-meso-HM-PAO after two minutes of i.v. administration, about 1.93% of I.D. appeared in the brain, and 24 hours later, 25% of radioactivity of I.D. was in the brain. This result shows that in the brain the radioactivity of 99m Tc-meso-HM-PAO declines faster than that of 99m Td-d,1-HM-PAO

  8. Generation of Reactive Astrocytes from NG2 Cells is Regulated by Sonic Hedgehog

    Czech Academy of Sciences Publication Activity Database

    Honsa, Pavel; Valný, Martin; Kriška, Ján; Matušková, Hana; Harantová, Lenka; Kirdajová, Denisa; Valihrach, Lukáš; Kubista, Mikael; Anděrová, Miroslava


    Roč. 64, č. 9 (2016), s. 1518-1531 ISSN 0894-1491 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GA16-10214S; GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) LQ1604; GA MŠk(CZ) EE2.3.30.0045 Institutional support: RVO:68378041 ; RVO:86652036 Keywords : ischemia * NG2 cells * glial scar Subject RIV: EB - Genetics ; Molecular Biology; EI - Biotechnology ; Bionics (BTO-N) Impact factor: 6.200, year: 2016

  9. Ablation of NG2 proteoglycan leads to deficits in brown fat function and to adult onset obesity.

    Directory of Open Access Journals (Sweden)

    Yunchao Chang

    Full Text Available Obesity is a major health problem worldwide. We are studying the causes and effects of obesity in C57Bl/6 mice following genetic ablation of NG2, a chondroitin sulfate proteoglycan widely expressed in progenitor cells and also in adipocytes. Although global NG2 ablation delays early postnatal adipogenesis in mouse skin, adult NG2 null mice are paradoxically heavier than wild-type mice, exhibiting larger white fat deposits. This adult onset obesity is not due to NG2-dependent effects on CNS function, since specific ablation of NG2 in oligodendrocyte progenitors yields the opposite phenotype; i.e. abnormally lean mice. Metabolic analysis reveals that, while activity and food intake are unchanged in global NG2 null mice, O(2 consumption and CO(2 production are decreased, suggesting a decrease in energy expenditure. Since brown fat plays important roles in regulating energy expenditure, we have investigated brown fat function via cold challenge and high fat diet feeding, both of which induce the adaptive thermogenesis that normally occurs in brown fat. In both tests, body temperatures in NG2 null mice are reduced compared to wild-type mice, indicating a deficit in brown fat function in the absence of NG2. In addition, adipogenesis in NG2 null brown pre-adipocytes is dramatically impaired compared to wild-type counterparts. Moreover, mRNA levels for PR domain containing 16 (PRDM16 and peroxisome proliferator-activated receptor γ coactivator (PGC1-α, proteins important for brown adipocyte differentiation, are decreased in NG2 null brown fat deposits in vivo and NG2 null brown pre-adipocytes in vitro. Altogether, these results indicate that brown fat dysfunction in NG2 null mice results from deficits in the recruitment and/or development of brown pre-adipocytes. As a consequence, obesity in NG2 null mice may occur due to disruptions in brown fat-dependent energy homeostasis, with resulting effects on lipid storage in white adipocytes.

  10. Radiative rates for E1, E2, M1 and M2 transitions in Fe X

    International Nuclear Information System (INIS)

    Aggarwal, K.M.; Keenan, F.P.


    Energies of the 54 levels belonging to the (1s 2 2s 2 2p 6 ) 3s 2 3p 5 , 3s3p 6 , 3s 2 3p 4 3d and 3s3p 5 3d configurations of Fe X have been calculated using the GRASP code of Dyall and colleagues (1989). Additionally, radiative rates, oscillator strengths, and line strengths are calculated for all electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2), and magnetic quadrupole (M2) transitions among these levels. Comparisons are made with results available in the literature, and the accuracy of the data is assessed. Our energy levels are estimated to be accurate to better than 3%, whereas results for other parameters are probably accurate to better than 20% . Additionally, the agreement between measured and calculated lifetimes is better than 10%. (authors)

  11. Tissue-specific expression and regulation by 1,25(OH)2D3 of chick protein kinase inhibitor (PKI) mRNA. (United States)

    Marchetto, G S; Henry, H L


    The heat-stable protein kinase inhibitor (PKI) protein is a specific and potent competitive inhibitor of the catalytic subunit of cAMP-dependent protein kinase (PKA). Previously, it has been shown that vitamin D status affects chick kidney PKI activity: a 5- to 10-fold increase in PKI activity was observed in kidneys of chronically vitamin D-deficient chicks and treatment with 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) in cultured kidney cells resulted in a 95% decrease in PKI activity. The authors have recently cloned the cDNA for chick kidney PKI and have used the coding sequence to study the regulation of PKI mRNA. Northern analysis showed the expression of two PKI messages, which are 2.7 and 3.3 kb in size. These mRNAs are expressed in brain, muscle, testis, and kidney, but not in pancreas, liver, or intestine. PKI mRNA steady-state levels are downregulated by 47% in kidneys from vitamin D-replete chicks as compared to vitamin D-deficient chicks. PKI mRNA levels in brain, muscle, and testis are not affected by vitamin D status. Treatment of primary chick kidney cultures treated with 10(-7) M 1,25(OH)2D3 for 24h resulted in a 20-30% decrease in PKI mRNA. 1,25(OH)2D3 treatment does not affect the stability of PKI mRNA as determined by treatment of cell cultures with actinomycin D. This study shows that 1,25(OH)2D3 directly and tissue-specifically downregulates PKI mRNA in the chick kidney.

  12. Rates of E1, E2, M1, and M2 transitions in Ni II (United States)

    Cassidy, C. M.; Hibbert, A.; Ramsbottom, C. A.


    Aims: We present rates for all E1, E2, M1, and M2 transitions among the 295 fine-structure levels of the configurations 3d9, 3d84s, 3d74s2, 3d84p, and 3d74s4p, determined through an extensive configuration interaction calculation. Methods: The CIV3 code developed by Hibbert and coworkers is used to determine for these levels configuration interaction wave functions with relativistic effects introduced through the Breit-Pauli approximation. Results: Two different sets of calculations have been undertaken with different 3d and 4d functions to ascertain the effect of such variation. The main body of the text includes a representative selection of data, chosen so that key points can be discussed. Some analysis to assess the accuracy of the present data has been undertaken, including comparison with earlier calculations and the more limited range of experimental determinations. The full set of transition data is given in the supplementary material as it is very extensive. Conclusions: We believe that the present transition data are the best currently available. Full Table 4 and Tables 5-8 are only available at the CDS via anonymous ftp to ( or via

  13. 2D numerical comparison between S{sub n} and M{sub 1} radiation transport methods

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, Matthias [Instituto de Fusion Nuclear, Universidad Politecnica de Madrid, calle Jose Gutierrez Abascal 2, 28006 Madrid (Spain)], E-mail:; Garcia-Fernandez, Carlos [Instituto de Fusion Nuclear, Universidad Politecnica de Madrid, calle Jose Gutierrez Abascal 2, 28006 Madrid (Spain)], E-mail:; Velarde, Pedro [Instituto de Fusion Nuclear, Universidad Politecnica de Madrid, calle Jose Gutierrez Abascal 2, 28006 Madrid (Spain)], E-mail:


    In this article we study the accuracy of the M{sub 1} method to solve some relevant radiation transport problems in 2D. We compare two radiation models (S{sub n} and M{sub 1}) with analytical and numerical tests to highlight the strengths and limitations of each method. These methods give comparable results except when sharp geometry effects are present. We have used these methods in a test that mimics, without fluid motion or electron heat conduction, the cone-target interaction relevant to inertial confinement fusion physics. In this case, we show that S{sub n} and M{sub 1} models agree with a quite good accuracy but shows differences in the temperature profiles and heating times inside the target. These results point out that M{sub 1} is a possible alternative candidate for 3D simulations, where full energy transport methods are extremely computer time consuming.

  14. Functional roles of CSPG4/NG2 in chondrosarcoma. (United States)

    Jamil, Nuor S M; Azfer, Asim; Worrell, Harrison; Salter, Donald M


    CSPG4/NG2 is a multifunctional transmembrane protein with limited distribution in adult tissues including articular cartilage. The purpose of this study was to investigate the possible roles of CSPG4/NG2 in chondrosarcomas and to establish whether this molecule may have potential for targeted therapy. Stable knock-down of CSPG4/NG2 in the JJ012 chondrosarcoma cell line by shRNA resulted in decreased cell proliferation and migration as well as a decrease in gene expression of the MMP (matrix metalloproteinase) 3 protease and ADAMTS4 (aggrecanase). Chondrosarcoma cells in which CSPG4/NG2 was knocked down were more sensitive to doxorubicin than wild-type cells. The results indicate that CSPG4/NG2 has roles in regulating chondrosarcoma cell function in relation to growth, spread and resistance to chemotherapy and that anti-CSPG4/NG2 therapies may have potential in the treatment of surgically unresectable chondrosarcoma. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  15. PSA Nadir of <0.5 ng/mL Following Brachytherapy for Early-Stage Prostate Adenocarcinoma is Associated With Freedom From Prostate-Specific Antigen Failure

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Eric C. [Department of Radiation Oncology, Mount Sinai Medical Center, New York, NY (United States); Stone, Nelson N. [Department of Radiation Oncology, Mount Sinai Medical Center, New York, NY (United States); Department of Urology, Mount Sinai Medical Center, New York, NY (United States); Stock, Richard G., E-mail: [Department of Radiation Oncology, Mount Sinai Medical Center, New York, NY (United States)


    Purpose: Because limited information exists regarding whether the rate or magnitude of PSA decline following brachytherapy predicts long-term clinical outcomes, we evaluated whether achieving a prostate-specific antigen (PSA) nadir (nPSA) <0.5 ng/mL following brachytherapy is associated with decreased PSA failure and/or distant metastasis. Methods and Materials: We retrospectively analyzed our database of early-stage prostate adenocarcinoma patients who underwent brachytherapy, excluding those receiving androgen-deprivation therapy and those with <2 years follow-up. Median and mean pretreatment PSA were 6 ng/mL and 7.16 ng/mL, respectively. By clinical stage, 775 were low risk ({<=}T2a), 126 were intermediate risk (T2b), and 20 were high risk (>T2b). By Gleason score, 840 were low risk ({<=}6), 71 were intermediate risk (7), and 10 were high risk (>7). Patients were treated with brachytherapy only (I-125, n = 779, or Pd-103, n = 47), or brachytherapy + external-beam radiation therapy (n = 95). Median follow-up was 6.3 years. We noted whether nPSA <0.5 ng/mL was achieved and the time to achieve this nadir and tested for associations with pretreatment risk factors. We also determined whether this PSA endpoint was associated with decreased PSA failure or distant metastasis. Results: Absence of high-risk factors in clinical stage ({<=}T2b), Gleason score ({<=}7), and pretreatment PSA ({<=}20 ng/mL) was significantly associated with achieving nPSA <0.5 ng/mL. By Kaplan-Meier analysis, patients achieving nPSA <0.5 ng/mL had significantly higher long-term freedom from biochemical failure (FFBF) than nonresponders (5-year FFBF: 95.2 {+-} 0.8% vs. 71.5 {+-} 6.7%; p < 0.0005). Among responders, those who achieved nPSA <0.5 ng/mL in {<=}5 years had higher FFBF than those requiring >5 years (5-year FFBF: 96.7 {+-} 0.7% vs. 80.8 {+-} 4.6%; p < 0.0005). On multivariate analysis, patients who achieved nPSA <0.5 ng/mL in {<=}5 years had significantly higher FFBF than other

  16. Production of HIV-1 vif mRNA Is Modulated by Natural Nucleotide Variations and SLSA1 RNA Structure in SA1D2prox Genomic Region

    Directory of Open Access Journals (Sweden)

    Masako Nomaguchi


    Full Text Available Genomic RNA of HIV-1 contains localized structures critical for viral replication. Its structural analysis has demonstrated a stem-loop structure, SLSA1, in a nearby region of HIV-1 genomic splicing acceptor 1 (SA1. We have previously shown that the expression level of vif mRNA is considerably altered by some natural single-nucleotide variations (nSNVs clustering in SLSA1 structure. In this study, besides eleven nSNVs previously identified by us, we totally found nine new nSNVs in the SLSA1-containing sequence from SA1, splicing donor 2, and through to the start codon of Vif that significantly affect the vif mRNA level, and designated the sequence SA1D2prox (142 nucleotides for HIV-1 NL4-3. We then examined by extensive variant and mutagenesis analyses how SA1D2prox sequence and SLSA1 secondary structure are related to vif mRNA level. While the secondary structure and stability of SLSA1 was largely changed by nSNVs and artificial mutations introduced to restore the original NL4-3 form from altered ones by nSNVs, no clear association of the two SLSA1 properties with vif mRNA level was observed. In contrast, when naturally occurring SA1D2prox sequences that contain multiple nSNVs were examined, we attained significant inverse correlation between the vif level and SLSA1 stability. These results may suggest that SA1D2prox sequence adapts over time, and also that the altered SA1D2prox sequence, SLSA1 stability, and vif level are mutually related. In total, we show here that the entire SA1D2prox sequence and SLSA1 stability critically contribute to the modulation of vif mRNA level.

  17. Relationship between vitamin D status and vascular complications in patients with type 2 diabetes mellitus. (United States)

    Jung, Chan-Hee; Kim, Kyu-Jin; Kim, Bo-Yeon; Kim, Chul-Hee; Kang, Sung Koo; Mok, Ji-Oh


    We aimed to investigate the association between serum 25-hydroxyvitamin D (25[OH]D) and microvascular complications in type 2 diabetes mellitus (T2DM) patients. It was hypothesized that lower 25(OH)D would be associated with increased microvascular complications in T2DM. A total of 257 T2DM patients (111 men, 146 women) who underwent diabetic microvascular complication (peripheral neuropathy, nephropathy, retinopathy) studies were recruited. Patients were categorized into 3 groups according to vitamin D status: vitamin D sufficient (n = 41, 25[OH]D ≥ 20 ng/mL), vitamin D insufficient (n = 132, 10 ≤ 25[OH]D 10 ng/mL). In men, the prevalence of diabetic peripheral neuropathy (DPN) was significantly higher in patients with vitamin D deficiency than in those with insufficiency or sufficiency (38%, 11.7%, and 10%, respectively; P = .005). In addition, the prevalence of diabetic nephropathy (DN) was significantly higher in women with vitamin D deficiency than in the other 2 groups (40%, 20.6%, and 0%; P = .007). Compared with men in the vitamin D-sufficient group (reference), men in the vitamin D-deficient group had an increased risk of DPN after adjusting for confounding factors (odds ratio, 7.79; 95% confidence interval, 1.52-40.05). For women, when the vitamin D-sufficient group was used as a reference, those in the vitamin D-deficient group had an increased risk of DN after adjusting for confounding factors (odds ratio, 4.27; 95% confidence interval, 1.58-11.56). This present study found that a serum 25(OH)D level less than 10 ng/mL is independently associated with increased DPN in male patients and increased DN in female patients with T2DM. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. ¿Es equivalente la suplementación diaria con vitamina D2 o vitamina D3 en adultos mayores?

    Directory of Open Access Journals (Sweden)

    Mariana Seijo


    Full Text Available Tanto la equivalencia entre colecalciferol (D3 y ergocalciferol (D2, como las dosis y forma de administración de ambos, son actualmente un tema controvertido. El objetivo de este estudio fue comparar la efectividad de 800 UI/día de D2 (gotas y D3 (comprimidos para alcanzar niveles adecuados de 25 hidroxivitamina D (25OHD (= 30 ng/ml. Veintiún mujeres posmenopáusicas que vivían en la Ciudad de Buenos Aires, edad promedio ( ± DS 77.1 ± 6.8 años fueron incluidas y asignadas en forma aleatoria a uno de los siguientes grupos: GD2 (n = 13: 800 UI (gotas y GD3 (n = 8: 800 UI (comprimidos. Se midió 25OHD sérica (RIA-DIASORIN basal y a los 7, 28 y 45 días del estudio. Basalmente, 19 de las 21 mujeres presentaron niveles de deficiencia de 25(OHD (< 20 ng/ml: GD2: 14.0 ± 4.8 y GD3: 13.2 ± 4.9 (NS. Se observó en el día 7 un incremento del ~25% solo en GD3 y un aumento significativo al final del estudio en ambos grupos, sin alcanzar los valores adecuados de 25OHD (GD2: 17.4 ± 5.5 vs. GD3:22.9 ± 4.6 ng/ml p < 0.001. La administración por 45 días de 800 UI de vitamina D3 fue más efectiva que D2 para incrementar los niveles de 25OHD, aunque ambas fueron insuficientes para alcanzar niveles adecuados de 25OHD (= 30 ng/ml.

  19. Pathophysiology of NG2-glia:a ‘Chicken and Egg’ scenario of altered neurotransmission and disruption of NG2-glial cell function


    Rivera, Andrea Domenico; De La Rocha, Irene Chacon; Neville, Rebekah; Butt, Arthur Morgan


    Classically, the central nervous system (CNS) was considered to contain neurons and three main types of glial cells - astrocytes, oligodendrocytes, and microglia. Now, it has been clearly established that NG2-glia are a fourth glial cell type that are defined by their expression of the NG2 chondroitin sulfate proteoglycan (Cspg4). NG2-glia are also known as oligodendrocyte precursor cells (OPCs) and express the alpha receptor for platelet-derived growth factor (Pdgfra) as well as other oligod...

  20. Vitamin D Assays and the Definition of Hypovitaminosis D: Results from the 1st International Conference on Controversies in Vitamin D. (United States)

    Sempos, Christopher T; Heijboer, Annemieke C; Bikle, Daniel D; Bollerslev, Jens; Bouillon, Roger; Brannon, Patsy M; DeLuca, Hector F; Jones, Glenville; Munns, Craig F; Bilezikian, John P; Giustina, Andrea; Binkley, Neil


    The 1st International Conference on Controversies in Vitamin D was held in Pisa, Italy June 14-16, 2017. The meeting's purpose was to address controversies in vitamin D research, review data available to help resolve them and suggest a research agenda to clarify areas of uncertainty. Serum 25-hydroxyvitamin D (25 (OH)D) concentration, i.e., the sum of 25 (OH)D 3 and 25 (OH)D 2 , remains the critical measurement for defining vitamin D status. Assay variation for 25 (OH) D has contributed to the current chaos surrounding efforts to define hypovitaminosis D. An essential requirement to develop consensus on vitamin D status is that measurement of 25 (OH) D and, in the future, other potential vitamin D biomarkers, e.g., 1α,25 (OH) 2 D 3 , 3-epi-25 (OH) D, 24,25 (OH) 2 D 3, vitamin D binding protein (DBP), free/bioavailable 25 (OH) D and parathyroid hormone be standardized/harmonized, to allow pooling of research data. Vitamin D Standardization Program (VDSP) tools are described and recommended for standardizing 25 (OH) D measurement in research. In the future, similar methodology, based on National Institute for Standards and Technology (NIST) Standard Reference Materials, must be developed for other candidate markers of vitamin D status. Failure to standardize/harmonize vitamin D metabolite measurements is destined to promulgate continued chaos. At this time, 25 (OH) D values below 12 ng/mL (30 nmol/L) should be considered to be associated with an increased risk of rickets/osteomalacia while 25 (OH) D concentrations between 20-50 ng/mL (50-125 nmol/L) appear to be safe and sufficient in the general population for skeletal health. In an effort to bridge knowledge gaps in defining hypovitaminosis D, an international study on rickets as a multifactorial disease is proposed. This article is protected by copyright. All rights reserved.

  1. Comparison of Analysis Results Between 2D/1D Synthesis and RAPTOR-M3G in the Korea Standard Nuclear Plant (KSNP

    Directory of Open Access Journals (Sweden)

    Lim Mi Joung


    Full Text Available The 2D/1D synthesis methodology has been used to calculate the fast neutron (E > 1.0 MeV exposure to the beltline region of the reactor pressure vessel. This method uses the DORT 3.1 discrete ordinates code and the BUGLE-96 cross-section library based on ENDF/B-VI. RAPTOR-M3G (RApid Parallel Transport Of Radiation-Multiple 3D Geometries which performs full 3D calculations was developed and is based on domain decomposition algorithms, where the spatial and angular domains are allocated and processed on multi-processor computer architecture. As compared to traditional single-processor applications, this approach reduces the computational load as well as the memory requirement per processor. Both methods are applied to surveillance test results for the Korea Standard Nuclear Plant (KSNP-OPR (Optimized Power Reactor 1000 MW. The objective of this paper is to compare the results of the KSNP surveillance program between 2D/1D synthesis and RAPTOR-M3G. Each operating KSNP has a reactor vessel surveillance program consisting of six surveillance capsules located between the core and the reactor vessel in the downcomer region near the reactor vessel wall. In addition to the In-Vessel surveillance program, an Ex-Vessel Neutron Dosimetry (EVND program has been implemented. In order to estimate surveillance test results, cycle-specific forward transport calculations were performed by 2D/1D synthesis and by RAPTOR-M3G. The ratio between measured and calculated (M/C reaction rates will be discussed. The current plan is to install an EVND system in all of the Korea PWRs including the new reactor type, APR (Advanced Power Reactor 1400 MW. This work will play an important role in establishing a KSNP-specific database of surveillance test results and will employ RAPTOR-M3G for surveillance dosimetry location as well as positions in the KSNP reactor vessel.

  2. Comparison of (/sup 125/I)beta-endorphin binding to rat brain and NG108-15 cells using a monoclonal antibody directed against the opioid receptor

    Energy Technology Data Exchange (ETDEWEB)

    Bidlack, J.M.; O' Malley, W.E.; Schulz, R.


    The properties of (/sup 125/I)beta h-endorphin-binding sites from rat brain membranes and membranes from the NG108-15 cell line were compared using a monoclonal antibody directed against the opioid receptor and opioid peptides as probes. The binding of (/sup 125/I)beta h-endorphin to both rat brain and NG108-15 membranes yielded linear Scatchard plots with Kd values of 1.2 nM and 1.5 nM, respectively, and Bmax values of 865 fmol/mg rat brain membrane protein and 1077 fmol/mg NG108-15 membrane protein. A monoclonal antibody, OR-689.2.4, capable of inhibiting mu and delta binding but not kappa binding to rat brain membranes, noncompetitively inhibited the binding of 1 nM (/sup 125/I)beta h-endorphin to rat brain and NG108-15 membranes with an IC50 value of 405 nM for rat brain membranes and 543 nM for NG108-15 membranes. The monoclonal antibody also inhibited the binding of 3 nM (/sup 3/H) (D-penicillamine2, D-penicillamine5) enkephalin to NG108-15 membranes with an IC50 value of 370 nM. In addition to blocking the binding of (/sup 125/I)beta h-endorphin to brain membranes, the antibody also displaced (/sup 125/I)beta h-endorphin from membranes. Site-specific opioid peptides had large variations in their IC50 values depending on whether they were inhibiting (/sup 125/I)beta h-endorphin binding to rat brain or the NG108-15 membranes. When the peptides were tested with the monoclonal antibody for their combined ability to inhibit (/sup 125/I)beta h-endorphin binding to both membrane preparations, the peptides and antibody blocked binding as though they were acting at allosterically coupled sites, not two totally independent sites. These studies suggest that mu-, delta-, and beta-endorphin-binding sites share some sequence homology with the 35,000-dalton protein that the antibody is directed against.

  3. Promiscuity of MCMV immunoevasin of NKG2D: m138/fcr-1 down-modulates RAE-1epsilon in addition to MULT-1 and H60. (United States)

    Arapović, Jurica; Lenac Rovis, Tihana; Reddy, Anil Butchi; Krmpotić, Astrid; Jonjić, Stipan


    Both human and mouse cytomegalovirus (CMV) encode proteins that inhibit the activation of NK cells by down-regulating the cellular ligands for activating NK cell receptor, NKG2D. MCMV proteins m145, m152 and m155 interfere with the expression of all known NKG2D ligands, MULT-1, RAE-1 family members and H60, respectively, whereas m138 affects the expression of MULT-1 and H60. Here we show that m152 affects the maturation of newly synthesized RAE-1 molecules, but is not sufficient to prevent surface expression of RAE-1varepsilon. We have identified m138 as a main inhibitor of the surface expression of RAE-1varepsilon. In contrast to m152, m138 affects the surface-resident protein leading to its endocytosis, which can be prevented by a dynamin inhibitor. Moreover, we demonstrated that m138 does not need other viral proteins to down-modulate the expression of RAE-1varepsilon.

  4. A simple and sensitive method for determination of vitamins D3 and K1 in rat plasma: application for an in vivo pharmacokinetic study. (United States)

    Gershkovich, Pavel; Ibrahim, Fady; Sivak, Olena; Darlington, Jerald W; Wasan, Kishor M


    To develop and to validate a simple but sensitive method for determination of vitamins D3 and K1 in rat plasma. The sample treatment included protein precipitation by cold acetonitrile, evaporation, reconstitution with methanol and filtration. The chromatography conditions included Xterra RP18 3.5 µm 4.6 × 100 mm column at ambient temperature and mobile phase consisting of methanol/water (93/7, v/v) at 0.5 mL/min flow rate. Vitamin D3 and probucol were detected at 265 nm and vitamin K1 at 239 nm. Rats were administered intravenously by 0.1 mg/kg of vitamin D3 or K1 and the blood samples were withdrawn pre-administration and at pre-determined time points post-administration. The pharmacokinetic analysis was performed using a non-compartmental approach. The calibration curves in rat plasma were linear up to 5000 ng/mL for both vitamins. The limit of quantification (LOQ) was 20 ng/mL for vitamin D3 and 40 ng/mL for K1. Inter- and intra-day precision and accuracy were below 15%. The pharmacokinetic parameters of vitamin D3 following intravenous administration were: AUC0-∞ = 11323 ± 1081 h × ng/mL, Vd = 218 ± 80 mL/kg, CL = 8.9 ± 0.8 mL/h/kg, t1/2 = 16.8 ± 5 h; and of vitamin K1: AUC0-∞ = 2495 ± 297 h × ng/mL, Vd = 60 ±24 mL/kg, CL = 40.5 ± 5.1mL/h/kg, t1/2 = 1.1 ±0.5 h. The developed HPLC-UV assay is a simple and sensitive method for the determination of vitamins D3 and K1 in rat plasma. A higher dose of vitamin K1 should be used in future studies for accurate estimation of pharmacokinetic parameters. The data show the suitability of the assay for pharmacokinetic studies in rats.

  5. Determination of vitamins D2, D3, K1 and K3 and some hydroxy metabolites of vitamin D3 in plasma using a continuous clean-up-preconcentration procedure coupled on-line with liquid chromatography-UV detection. (United States)

    Ortiz Boyer, F; Fernández Romero, J M; Luque de Castro, M D; Quesada, J M


    A semi-automatic procedure for the continuous clean-up and concentration of several fat-soluble vitamins prior to their separation by HPLC and UV detection is reported. The procedure is based on the use of a minicolumn packed with aminopropylsilica as sorbent located prior to the chromatographic detection system. The overall process was developed and applied to the main liposoluble vitamins (A, D2, D3, E, K1, K3) and several hydroxy metabolites of vitamin D3 [25-(OH)-D3,24,25-(OH)2-D3 and 1,25-(OH)2-D3]. All the analytes were monitored at a compromise wavelength of 270 nm. Calibration graphs were constructed between 0.01 and 100 ng ml-1 for vitamin D2 and D3 and their hydroxy metabolites, between 0.1 and 100 ng ml-1 for vitamin A, K1 and K3 and between 1 and 100 ng ml-1 for vitamin E, with excellent regression coefficients (> or = 0.9901) in all cases. The precision was established at two concentration levels with acceptable RSDs in all instances (between 3.6 and 8.7%). The method was appropriate for the determination of vitamin D2, D3, K1 and K3 and the 24,25-dihydroxy and 25-hydroxy metabolites of vitamin D3 in human plasma. The method was applied to plasma samples spiked with the target analytes and the recoveries ranged between 78 and 109%.

  6. Stage T1-2 prostate cancer with pretreatment PSA 10 ng/ml or less: radiotherapy or surgery?

    International Nuclear Information System (INIS)

    Keyser, Douglas; Kupelian, Patrick; Zippe, Craig; Klein, Eric


    Purpose: Presently, patients with pretreatment PSA levels ≤10 ng/ml constitute the majority of cases presenting for definitive treatment. Our aim was to determine whether the type of treatment (radiotherapy versus surgery) affected biochemical failure rates in this group of patients. This study is based on 389 patients treated at a single institution. Material and Methods: The charts of all patients treated with either radiotherapy or prostatectomy alone between 1987 and 1993 were reviewed (n=811). Patients with clinical stage T1 or T2 disease, and a pretreatment PSA level (iPSA) of 10.0 or less were analyzed (n=389). Two hundred forty nine (64%) received radical prostatectomy and 140 (36%) received radiotherapy (median dose 66.6 Gy). Pretreatment patient characteristics including clinical stage, biopsy Gleason score (GS) and iPSA level were not significantly different between the radiation and surgery groups (Table 1). The patients treated with radiation were significantly older (median age 70 years vs. 64 years, p<0.05). A total of 37% of the prostatectomy patients had a positive margin. The median follow-up time was 33 months; 1458 follow-up PSA levels were available for analysis. Biochemical failure was defined as a rise in PSA level of 1.0 ng/ml above the nadir PSA level in radiotherapy cases, or any value above 0.2 ng/ml in the prostatectomy cases. Results: The overall 5 year actuarial biochemical relapse free survival (bRFS) rate was 70%. The 5-year bRFS rates for prostatectomy and radiotherapy were identical (70%) (Fig.1). The significant factors affecting bRFS rates were iPSA level (≤4 vs. 4-10 ng/ml) and Gleason score (≤6 vs. ≥7) (Table 2). The 5-year bRFS rates of patients with iPSA ≤4 vs. iPSA 4-10 ng/ml were 92% vs. 61% respectively, p<0.01. The 5-year clinical relapse free survival was 93%. All clinical failures were preceded by biochemical failure. Patients with positive surgical margins did significantly worse than those with negative

  7. Understanding the NG2 glial scar after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Amber R Hackett


    Full Text Available NG2 cells, also known as oligodendrocyte progenitor cells, are located throughout the central nervous system and serve as a pool of progenitors to differentiate into oligodendrocytes. In response to spinal cord injury, NG2 cells increase their proliferation and differentiation into remyelinating oligodendrocytes. While astrocytes are typically associated with being the major cell type in the glial scar, many NG2 cells also accumulate within the glial scar but their function remains poorly understood. Similar to astrocytes, these cells hypertrophy, upregulate expression of chondroitin sulfate proteoglycans, inhibit axon regeneration, contribute to the glial-fibrotic scar border, and some even differentiate into astrocytes. Whether NG2 cells also have a role in other astrocyte functions, such as preventing the spread of infiltrating leukocytes and expression of inflammatory cytokines, is not yet known. Thus, NG2 cells are not only important for remyelination after spinal cord injury, but are also a major component of the glial scar with functions that overlap with astrocytes in this region. In this review, we describe the signaling pathways important for the proliferation and differentiation of NG2 cells, as well as the role of NG2 cells in scar formation and tissue repair.

  8. Comparison of the uptake of [123/125I]-2-iodo-D-tyrosine and [123/125I]-2-iodo-L-tyrosine in R1M rhabdomyosarcoma cells in vitro and in R1M tumor-bearing Wag/Rij rats in vivo

    International Nuclear Information System (INIS)

    Bauwens, Matthias; Lahoutte, Tony; Kersemans, Ken; Gallez, Carol; Bossuyt, Axel; Mertens, John


    Introduction: Recently, promising results concerning uptake in vivo in tumors of D-amino acids have been published. Therefore, we decided to evaluate the tumor uptake of the D-analogue of [ 123 I]-2-iodo-L-tyrosine, a tracer recently introduced by our group into clinical trials. The uptake of 2-amino-3-(4-hydroxy-2-[ 123/125 I]iodophenyl)-D-propanoic acid (2-iodo-D-tyrosine) was studied in vitro in LAT1-expressing R1M rat rhabdomyosarcoma cells and in vivo in R1M tumor-bearing Wag/Rij rats. Methods: The uptake of [ 125 I]-2-iodo-L-tyrosine and [ 125 I]-2-iodo-D-tyrosine into R1M cells was determined in appropriate buffers, allowing the study of the involved transport systems. In vivo, the biodistribution in R1M-bearing rats of [ 123 I]-2-iodo-L-tyrosine and [ 123 I]-2-iodo-D-tyrosine was performed by both dynamic and static planar imaging with a gamma camera. Results: In in vitro conditions, the uptake of both [ 125 I]-2-iodo-L-tyrosine and [ 125 I]-2-iodo-D-tyrosine in the HEPES buffer was 25% higher in the presence of Na + ions. In the absence of Na + ions, [ 125 I]-2-iodo-D-tyrosine was taken up reversibly in the R1M cells, with an apparent accumulation, probably for the larger part by the LAT1 system. Dynamic planar imaging showed that the uptake in the tumors of [ 123 I]-2-iodo-D-tyrosine was somewhat lower than that of [ 123 I]-2-iodo-L-tyrosine. At 30 min postinjection, the mean differential uptake ratio values of the L- and D-enantiomers are 2.5±0.7 and 1.7±0.6, respectively. Although the uptake of the D-isomer is lower, probably due to a faster clearance from the blood, the tumor-background ratio is the same as that of the L-analogue. Conclusion: A large part (75%) of [ 125 I]-2-iodo-D-tyrosine in vitro and [ 123 I]-2-iodo-D-tyrosine in vivo is reversibly highly taken up in R1M tumor cells by Na + -independent LAT transport systems, more likely by the LAT1. The clearance from the blood of [ 123 I]-2-iodo-D-tyrosine in the rats is faster than that of the

  9. High-Risk Prostate Cancer With Gleason Score 8–10 and PSA Level ≤15 ng/ mL Treated With Permanent Interstitial Brachytherapy

    International Nuclear Information System (INIS)

    Fang, L. Christine; Merrick, Gregory S.; Butler, Wayne M.; Galbreath, Robert W.; Murray, Brian C.; Reed, Joshua L.; Adamovich, Edward; Wallner, Kent E.


    Purpose: With widespread prostate-specific antigen (PSA) screening, there has been an increase in men diagnosed with high-risk prostate cancer defined by a Gleason score (GS) ≥8 coupled with a relatively low PSA level. The optimal management of these patients has not been defined. Cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) were evaluated in brachytherapy patients with a GS ≥8 and a PSA level ≤15 ng/mL with or without androgen-deprivation therapy (ADT). Methods and Materials: From April 1995 to October 2005, 174 patients with GS ≥8 and a PSA level ≤15 ng/mL underwent permanent interstitial brachytherapy. Of the patients, 159 (91%) received supplemental external beam radiation, and 113 (64.9%) received ADT. The median follow-up was 6.6 years. The median postimplant Day 0 minimum percentage of the dose covering 90% of the target volume was 121.1% of prescription dose. Biochemical control was defined as a PSA level ≤0.40 ng/mL after nadir. Multiple parameters were evaluated for impact on survival. Results: Ten-year outcomes for patients without and with ADT were 95.2% and 92.5%, respectively, for CSS (p = 0.562); 86.5% and 92.6%, respectively, for bPFS (p = 0.204); and 75.2% and 66.0%, respectively, for OS (p = 0.179). The median post-treatment PSA level for biochemically controlled patients was <0.02 ng/mL. Multivariate analysis failed to identify any predictors for CSS, whereas bPFS and OS were most closely related to patient age. Conclusions: Patients with GS ≥8 and PSA level ≤15 ng/mL have excellent bPFS and CSS after brachytherapy with supplemental external beam radiotherapy. The use of ADT did not significantly impact bPFS, CSS, or OS.

  10. Sunlight–derived vitamin D affects interleukin-4 level, T helper 2 serum cytokines, in patients with Graves’ disease: a prospective cohort study

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    Dyah Purnamasari


    Full Text Available Background: Graves’ disease (GD is the most common autoimmune disease leading to hyperthyroidism. The role of Th1/Th2 pathways balance in GD is still controversial. Vitamin D is reported to have an effect on those pathways. This study aims to examine the effect of sunlight exposure on vitamin D 25(OH level and Th1 and Th2 pathway-derived cytokines in GD patients. Methods: A prospective cohort study was conducted on 32 GD patients to compare the effect of sunlight exposure on vitamin D level and cytokines of Th1 and Th2 pathways between exposed and unexposed groups. Exposed group received sunlight exposure three times a week for 30 minutes each between 9–11 a.m for 1 month. Thyroid stimulating hormone (TSH, free thyroxin (fT4, vitamin D 25(OH, interferon-γ (IFN-γ and interleukin-4 (IL-4 serum levels, were investigated before and after one month of sunlight exposure. Paired t-test or Mann Whitney test were used to analyze the difference between exposed and unexposed GD groups before and after sun exposure.Results: One month of sunlight exposure increased vitamin D 25(OH level by 27.90% among exposed GD group (15.34 ng/mL to 19.62 ng/mL, p<0.001. Meanwhile, unexposed GD group’s vitamin D 25(OH level decreased from 20.48 ng/mL to 18.86 ng/mL (p<0.001. Increased vitamin D 25(OH level in exposed group was not accompanied by the increase of IL-4 level after sunlight exposure.Conclusion: Sunlight exposure increases vitamin D 25(OH serum level and may affect the level of IL-4, Th2 pathway-derived cytokine, in patients with GD. However, the role of sunlight-derived vitamin D on IFN-γ in GD patients can not be concluded in this study.

  11. ¿Es equivalente la suplementación diaria con vitamina D2 o vitamina D3 en adultos mayores? Is daily supplementation with vitamin D2 equivalent to daily supplementation with vitamin D3 in the elderly?

    Directory of Open Access Journals (Sweden)

    Mariana Seijo


    Full Text Available Tanto la equivalencia entre colecalciferol (D3 y ergocalciferol (D2, como las dosis y forma de administración de ambos, son actualmente un tema controvertido. El objetivo de este estudio fue comparar la efectividad de 800 UI/día de D2 (gotas y D3 (comprimidos para alcanzar niveles adecuados de 25 hidroxivitamina D (25OHD (= 30 ng/ml. Veintiún mujeres posmenopáusicas que vivían en la Ciudad de Buenos Aires, edad promedio ( ± DS 77.1 ± 6.8 años fueron incluidas y asignadas en forma aleatoria a uno de los siguientes grupos: GD2 (n = 13: 800 UI (gotas y GD3 (n = 8: 800 UI (comprimidos. Se midió 25OHD sérica (RIA-DIASORIN basal y a los 7, 28 y 45 días del estudio. Basalmente, 19 de las 21 mujeres presentaron niveles de deficiencia de 25(OHD (The equivalence of cholecalciferol (D3 and ergocalciferol (D2 as well as their corresponding doses and administration route remain controversial to date. The aim of this study was to compare the effectiveness of daily supplementation with 800 IU of D2 (drops and D3 (pills on 25-hydroxivitamin D (25OHD levels (= 30 ng/ml. Twenty-one ambulatory postmenopausal women from Buenos Aires City with a mean ( ± SD age of 77.1 ± 6.8 years were included. The participants were randomly assigned to one of the following groups: GD2 (n = 13: 800 IU (drops and GD3 (n = 8: 800 IU (pills. Serum 25OHD levels were measured (RIA-DIASORIN at baseline, and at 7, 28 and 45 days. Nineteen out of twenty one women showed deficient levels of 25OHD at baseline (< 20 ng/ml: GD2: 14.0 ± 4.8 ng/ml and GD3: 13.2 ± 4.9 ng/ml (NS. Whereas only GD3 exhibited an increase (~25% at 7 days, both groups showed a significant increase at the end of the study. However, neither attained adequate 25OHD levels (GD2: 17.4 ± 5.5 vs. GD3:22.9 ± 4.6 ng/ml; p < 0.001. Administration of 800 IU of vitamin D3 during 45 days was more effective than D2 in increasing 25OHD, but both failed to achieve adequate levels of 25OHD (= 30 ng/ml. but neither

  12. Vitamin D Deficiency in Relation to the Risk of Metabolic Syndrome in Middle-Aged and Elderly Patients with Type 2 Diabetes Mellitus. (United States)

    Pan, Guo-Tao; Guo, Jian-Feng; Mei, Shao-Lin; Zhang, Meng-Xi; Hu, Zhi-Yong; Zhong, Chong-Ke; Zeng, Chang-You; Liu, Xiao-Hong; Ma, Qing-Hua; Li, Bing-Yan; Qin, Li-Qiang; Zhang, Zeng-Li


    Vitamin D deficiency is highly prevalent all over the world and dietary intakes of vitamin D are very low in China. In this study we aimed to determine whether vitamin D deficiency is associated with increased risk of metabolic syndrome (MetS) among Chinese type 2 diabetes mellitus (T2DM) patients aged over 50 y. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured in a cross-sectional sample of 270 T2DM patients aged over 50 y from Zhejiang. Data on demographic characteristics, anthropometry and other variables were collected. The mean of serum 25(OH)D was 22.93 ng/mL, and percentages of vitamin D deficiency and insufficiency were 43.71% and 39.63%, respectively. Serum 25(OH)D concentrations were significantly lower in subjects with MetS than in those without MetS (21.74 vs 24.96 ng/mL, p=0.001), and the prevalence of MetS significantly increased according to tertiles of serum 25(OH)D concentrations. After adjusting for multivariate factors, the adverse effect of lower serum 25(OH)D concentrations was significant (OR: 3.26, 95% CI: 1.03-7.34; p=0.044) in the group with BMI≥24 kg/m 2 while the change in OR of MetS for each 10 ng/mL decrease in the serum 25(OH)D concentrations was 2.03 (95% CI: 1.10-3.79). These results suggest that serum 25(OH)D deficiency may be a risk factor of MetS among Chinese type 2 diabetic patients, especially in the T2DM with BMI≥24 kg/m 2 . The challenge is determining the mechanisms of vitamin D action for recommendation of vitamin D supplementation that reduces the risks of MetS and progression to T2DM.

  13. M2 to D2

    International Nuclear Information System (INIS)

    Mukhi, Sunil; Papageorgakis, Constantinos


    We examine the recently proposed ''3-algebra'' field theory for multiple M2-branes and show that when a scalar field valued in the 3-algebra develops a vacuum expectation value, the resulting Higgs mechanism has the novel effect of promoting topological (Chern-Simons) to dynamical (Yang-Mills) gauge fields. This leads to a precise derivation of the maximally supersymmetric Yang-Mills theory on multiple D2-branes and thereby provides a relationship between 3-algebras and Yang-Mills theories. We discuss the physical interpretation of this result.

  14. Homoleptic diphosphacyclobutadiene complexes [M(η(4)-P2C2R2)2]x- (M = Fe, Co; x = 0, 1). (United States)

    Wolf, Robert; Ehlers, Andreas W; Khusniyarov, Marat M; Hartl, František; de Bruin, Bas; Long, Gary J; Grandjean, Fernande; Schappacher, Falko M; Pöttgen, Rainer; Slootweg, J Chris; Lutz, Martin; Spek, Anthony L; Lammertsma, Koop


    The preparation and comprehensive characterization of a series of homoleptic sandwich complexes containing diphosphacyclobutadiene ligands are reported. Compounds [K([18]crown-6)(thf)(2)][Fe(η(4)-P(2)C(2)tBu(2))(2)] (K1), [K([18]crown-6)(thf)(2)][Co(η(4)-P(2)C(2)tBu(2))(2)] (K2), and [K([18]crown-6)(thf)(2)][Co(η(4)-P(2)C(2)Ad(2))(2)] (K3, Ad = adamantyl) were obtained from reactions of [K([18]crown-6)(thf)(2)][M(η(4)-C(14)H(10))(2)] (M = Fe, Co) with tBuC[triple bond]P (1, 2), or with AdC[triple bond]P (3). Neutral sandwiches [M(η(4)-P(2)C(2)tBu(2))(2)] (4: M = Fe 5: M = Co) were obtained by oxidizing 1 and 2 with [Cp(2)Fe]PF(6). Cyclic voltammetry and spectro-electrochemistry indicate that the two [M(η(4)-P(2)C(2)tBu(2))(2)](-)/[M(η(4)-P(2)C(2)tBu(2))(2)] moieties can be reversibly interconverted by one electron oxidation and reduction, respectively. Complexes 1-5 were characterized by multinuclear NMR, EPR (1 and 5), UV/Vis, and Mössbauer spectroscopies (1 and 4), mass spectrometry (4 and 5), and microanalysis (1-3). The molecular structures of 1-5 were determined by using X-ray crystallography. Essentially D(2d)-symmetric structures were found for all five complexes, which show the two 1,3-diphosphacyclobutadiene rings in a staggered orientation. Density functional theory calculations revealed the importance of covalent metal-ligand π bonding in 1-5. Possible oxidation state assignments for the metal ions are discussed.

  15. Neutron flux stabilization in the NG-150 neutron generators

    International Nuclear Information System (INIS)

    Kuz'min, L.E.; Makarov, S.A.; Pronman, I.M.


    Problem of metal tritium target lifetime increase and neutron flux stabilization in the NG-150 neutron generators is studied. Possibility on neutron flux stabilization using the mass analyzer for low-angle (4 deg and 41 deg) mass separation of a beam in thre components, which fall on a target simultaneously, is confirmed experimentally. Basic generator parameters are: accelerating voltage of 150 kV, total beam current on a target of 1.5 mA, beam current density of 0.3-1.6 mA/cm 2 , beam diameter of 8 mm. The initial neutron flux on the targets of 0.73 mg/cm 2 thick constituted 1.1x10 11 ssup(-1). The neutron flux monitoring was accomplished from recoil proton recording by a plastic scintillator. Flux decrease by more than 5% served as a signel for measuring mass analyzer magnetic field providing beam displacement on a target and restoration of the given flux. The NG-150 generator neutron flux stabilization was attained during 2h

  16. Spectroscopic Studies of Semiconductor Materials for Aggressive-scaled Micro- and Opto-electronic Devices: nc-SiO2, GeO2; ng-Si, Ge and ng-Transition metal (TM) oxides (United States)

    Cheng, Cheng

    transitions. Intra-d states are observed in all high-K dielectrics regardless of morphology, e.g. ng-TiO2, nc- Ti silicate , c-LaTiO3, nc-HfSiON334. This dissertation also discussed spectroscopic studies of: (i) nc-SiO 2, nc-GeO2 and (ii) nc-(SiO2)x(GeO2) 1-x pseudo-binary alloys. These studies, and the interpretation of these spectra and those in Chapter 3 in the This dissertation also discussed spectroscopic studies of: (i) nc-SiO2, nc-GeO2 and (ii) nc-(SiO 2)x(GeO2)1-x pseudo-binary alloys. These studies, and the interpretation of these spectra and those in Chapter 3 in the context of ab-initio theory provide a science base for the implementation of nc-oxides onto Germaniumsubstrates for aggressively scaled CMOS FETs, imaging devices as well as photovoltaics. X-Ray photoelectron spectroscopy(XPS) and Auger electron spectroscopy(AES) were used to determine SiO2 and GeO2 concentration in (SiO2)x(GeO2)1-x alloys. A linear trend in chemical shifts with compositions is observed and explained with charge-potential model, which incorporates the results of calculated partial charge from an empirical model for ionicity. The compositional linear relationships between binding energies nc-SiO 2, nc-GeO2, and (SiO2)x(GeO2)1-x alloy concentration agrees with the calculated results in charge potential model. SE and XAS spectral results show relatively strong O-vacancy in nc-GeO 2. O-vacancy defects in c-SiO2 are weaker. This is due to differences between Ge-O and Si-O bond (657.5kJ/mol and 799.6kJ/mol respectively). SE data shows a strong defect feature in GeO2, while SiO2 has no significant and distinct defect signature. Percolation theory describes the interconnection of bonds, e.g. Si-O and Ge-O in an otherwise nc-material, a (SiO2)x(GeO2)1-x pseudo-binary alloy. Changes in the band-gap energy of binary Si-Ge alloys occur at 0%Si (or 100% Ge), and the band gap energy increases from ˜ 0.6 eV to ˜0.87 eV as the Si concentration increases. A inflection point is at the percolation

  17. 1.2V, 24mW/ch, 10bit, 80MSample/s Pipelined A/D Converters (United States)

    Ueno, Takeshi; Ito, Tomohiko; Kurose, Daisuke; Yamaji, Takafumi; Itakura, Tetsuro

    This paper describes 10-bit, 80-MSample/s pipelined A/D converters for wireless-communication terminals. To reduce power consumption, we employed the I/Q amplifier sharing technique [1] in which an amplifier is used for both I and Q channels. In addition, common-source, pseudo-differential (PD) amplifiers are used in all the conversion stages for further power reduction. Common-mode disturbances are removed by the proposed common-mode feedforward (CMFF) technique without using fully differential (FD) amplifiers. The converter was implemented in a 90-nm CMOS technology, and it consumes only 24mW/ch from a 1.2V power supply. The measured SNR and SNDR are 58.6dB and 52.2dB, respectively.

  18. M(4-PridinkarboksialdehidNi(CN4.nG Hofmann Tipi Konak-Konuk Bileşiklerinin Kırmızıaltı Spektroskopik Özelliklerinin İncelenmesi (M = Ni, Cd ve G = 1,4-Dioksan

    Directory of Open Access Journals (Sweden)

    Zeki KARTAL


    M(4-PyridinecarboxaldehydeNi(CN4.nG Hofmann Type Clathrates (M = Ni, Cd and G = 1,4-Dioxane Abstract: In this study, clathrate of 4-pyridinecarboxaldehyde tetracyanonickel-dioxane, given by the formula M(4-PyridinecarboxaldehydeNi(CN4 nG (m = Ni, Cd and G = 1,4-dioxane, is obtained for the first time through chemical methods. The FT-IR spectroscopic data in the region of (3000–400 cm-1 was recorded and the IR vibrational modes frequencies were given and explained in detail. The spectral analyzes results of the newly synthesized clathrate of 4-pyridinecarboxaldehyde tetracyanonickel- dioxane suggests that these clathrates are new examples of the Hofmann-type dioxane clathrates. In our study, the Hofmann-type dioxane clathrates formed by bounding electrons of nitrogen-donor atom of pyridine ring and electrons of oxygen-donor atom of aldehyde group (-CH=O of 4-pyridinecarboxaldehyde ligand molecule to transition metal atoms consist of the corrugated |M–Ni(CN4|ï‚¥ polymeric layers which are held in parallel through the chain of (–M–4PCA–M–. Key words: Infrared Spectroscopy, Hofmann Types Clathrates, Tetracyanonickelate, 4-pyridinecarboxaldehyde, 1,4-dioxane

  19. Nested 1D-2D approach for urban surface flood modeling (United States)

    Murla, Damian; Willems, Patrick


    Floods in urban areas as a consequence of sewer capacity exceedance receive increased attention because of trends in urbanization (increased population density and impermeability of the surface) and climate change. Despite the strong recent developments in numerical modeling of water systems, urban surface flood modeling is still a major challenge. Whereas very advanced and accurate flood modeling systems are in place and operation by many river authorities in support of flood management along rivers, this is not yet the case in urban water management. Reasons include the small scale of the urban inundation processes, the need to have very high resolution topographical information available, and the huge computational demands. Urban drainage related inundation modeling requires a 1D full hydrodynamic model of the sewer network to be coupled with a 2D surface flood model. To reduce the computational times, 0D (flood cones), 1D/quasi-2D surface flood modeling approaches have been developed and applied in some case studies. In this research, a nested 1D/2D hydraulic model has been developed for an urban catchment at the city of Gent (Belgium), linking the underground sewer (minor system) with the overland surface (major system). For the overland surface flood modelling, comparison was made of 0D, 1D/quasi-2D and full 2D approaches. The approaches are advanced by considering nested 1D-2D approaches, including infiltration in the green city areas, and allowing the effects of surface storm water storage to be simulated. An optimal nested combination of three different mesh resolutions was identified; based on a compromise between precision and simulation time for further real-time flood forecasting, warning and control applications. Main streets as mesh zones together with buildings as void regions constitute one of these mesh resolution (3.75m2 - 15m2); they have been included since they channel most of the flood water from the manholes and they improve the accuracy of

  20. The effects of 1α, 25-dihydroxyvitamin D3 and transforming growth factor-β3 on bone development in an ex vivo organotypic culture system of embryonic chick femora.

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    Emma L Smith

    Full Text Available Transforming growth factor-beta3 (TGF-β3 and 1α,25-dihydroxyvitamin D3 (1α,25 (OH 2D3 are essential factors in chondrogenesis and osteogenesis respectively. These factors also play a fundamental role in the developmental processes and the maintenance of skeletal integrity, but their respective direct effects on these processes are not fully understood. Using an organotypic bone rudiment culture system the current study has examined the direct roles the osteotropic factors 1α,25 (OH2D3 and TGF-β3 exert on the development and modulation of the three dimensional structure of the embryonic femur. Isolated embryonic chick femurs (E11 were organotypically cultured for 10 days in basal media, or basal media supplemented with either 1α,25 (OH 2D3 (25 nM or TGF-β3 (5 ng/mL & 15 ng/mL. Analyses of the femurs were undertaken using micro-computed tomography (μCT, histology and immunohistochemistry. 1α,25 (OH2D3 supplemented cultures enhanced osteogenesis directly in the developing femurs with elevated levels of osteogenic markers such as type 1 collagen. In marked contrast organotypic femur cultures supplemented with TGF-β3 (5 ng/mL & 15 ng/mL demonstrated enhanced chondrogenesis with a reduction in osteogenesis. These studies demonstrate the efficacy of the ex vivo organotypic embryonic femur culture employed to elucidate the direct roles of these molecules, 1α,25 (OH 2D3 and TGF-β3 on the structural development of embryonic bone within a three dimensional framework. We conclude that 1α,25(OH2D and TGF-β3 modify directly the various cell populations in bone rudiment organotypic cultures effecting tissue metabolism resulting in significant changes in embryonic bone growth and modulation. Understanding the roles of osteotropic agents in the process of skeletal development is integral to developing new strategies for the recapitulation of bone tissue in later life.

  1. Association between Circulating Vitamin D Level and Urolithiasis: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Henglong Hu


    Full Text Available Many studies compared the serum/plasma 1,25 dihydroxyvitamin D3 (1,25(OH2D and 25 hydroxyvitamin D3 (25(OHD between people with and without nephrolithiasis, and their results were conflicting. After systematically searching PubMed, Web of Science, The Cochrane Library, CNKI, and the Wanfang Database, we conducted a meta-analysis. Thirty-two observational studies involving 23,228 participants were included. Meta-analysis of these studies showed that of stone formers (SFs, calcium SFs had significantly higher concentrations of 1,25(OH2D (weighted mean difference (WMD, 10.19 pg/mL; 95% confidence interval (CI, 4.31–16.07; p = 0.0007 and WMD, 11.28 pg/mL; 95% CI, 4.07–18.50; p = 0.002, respectively than non-stone formers, while the levels of 25(OHD (WMD, 0.88 ng/mL; 95% CI, −1.04–2.80; p = 0.37 and WMD, −0.63 ng/mL; 95% CI, −2.72–1.47; p = 0.56, respectively are similar. Compared with controls and normocalciuria SFs, hypercalciuria SFs had increased circulating 1,25(OH2D (WMD, 9.41 pg/mL; 95% CI, 0.15–18.67; p = 0.05 and WMD, 2.75 pg/mL; 95% CI, −0.20–5.69; p = 0.07, respectively and markedly higher 25(OHD (WMD, 5.02 ng/mL; 95% CI, 0.99–9.06; p = 0.01 and WMD, 5.02 ng/mL; 95% CI, 2.14–7.90; p = 0.0006, respectively. Normocalciuria SFs had elevated 1,25(OH2D level (WMD, 6.85 pg/mL; 95% CI, −5.00–18.71; p = 0.26 and comparable 25(OHD (WMD, 0.94 ng/mL; 95% CI, −3.55–5.43; p = 0.68. Sensitivity analysis generated similar results. Current evidence suggests that increased circulating 1,25(OH2D is associated with urinary stones and a higher level of circulating 25(OHD is significantly associated with hypercalciuria urolithiasis. Further studies are still needed to reconfirm and clarify the role of vitamin D in the pathogenesis of stones.

  2. Puuduv lugu, ainult kangelane : Zidane ja kunsti mäng / Zoe Stillpass

    Index Scriptorium Estoniae

    Stillpass, Zoe


    Režissööride Philippe Parreno ja Douglas Gordoni film prantsuse jalgpallurist Zinedine Zidanest. Film on 23. aprillil 2005 peetud mäng Real Madridi ja Villareali vahel Madridis, mida filmiti 17 kaameraga, mis kõik olid fokusseeritud Zidane'ile. Helitaust pärineb šoti alternatiivroki bändilt Mogwai

  3. Multipole induced splitting of metal-cage vibrations in crystalline endohedral D2d-M2@C84 dimetallofullerenes. (United States)

    Krause, M; Popov, V N; Inakuma, M; Tagmatarchis, N; Shinohara, H; Georgi, P; Dunsch, L; Kuzmany, H


    Metal-carbon cage vibrations of crystalline endohedral D2d-M2@C84 (M=Sc,Y,Dy) dimetallofullerenes were analyzed by temperature dependent Raman scattering and a dynamical force field model. Three groups of metal-carbon cage modes were found at energies of 35-200 cm(-1) and assigned to metal-cage stretching and deformation vibrations. They exhibit a textbook example for the splitting of molecular vibrations in a crystal field. Induced dipole-dipole and quadrupole-quadrupole interactions account quantitatively for the observed mode splitting. Based on the metal-cage vibrational structure it is demonstrated that D2d-Y2@C84 dimetallofullerene retains a monoclinic crystal structure up to 550 K and undergoes a transition from a disordered to an ordered orientational state at a temperature of approximately 150 K.

  4. Floodplain simulation for Musi River using integrated 1D/2D hydrodynamic model

    Directory of Open Access Journals (Sweden)

    Al Amin Muhammad B.


    Full Text Available This paper presents the simulation of floodplain at Musi River using integrated 1D and 2D hydrodynamic model. The 1D flow simulation was applied for the river channel with flow hydrograph as upstream boundary condition. The result of 1D flow simulation was integrated into 2D flow simulation in order to know the area and characteristics of flood inundation. The input data of digital terrain model which was used in this research had grid resolution of 10m×10m, but for 2D simulation the resolution was with grid resolution 50 m × 50 m so as to limit simulation time since the model size was big enough. The result of the simulation showed that the inundated area surrounding Musi River is about 107.44 km2 with maximum flood depth is 3.24 m, water surface velocity ranges from 0.00 to 0.83 m/s. Most of floodplain areas varied from middle to high flood hazard level, and only few areas had very high level of flood hazard especially on river side. The structural flood control measurement to be recommended to Palembang is to construct flood dike and flood gate. The non structural measurement one is to improve watershed management and socialization of flood awareness.

  5. I nducin ng and d ident ifying in b artifici banana ially-in as nduced d ...

    African Journals Online (AJOL)


    520. Stover RH, Simmonds NW(1987). Bananas. Third Edition. Longman,. London. Vakili NG (1962). Colchicine-induced polyploidy in Musa. Nature 194: 453-454. Van Duren M, Morpurgo R, Dolezel J Afza R (1996). Induction and verification of ...

  6. Enhanced M1/M2 macrophage ratio promotes orthodontic root resorption. (United States)

    He, D; Kou, X; Luo, Q; Yang, R; Liu, D; Wang, X; Song, Y; Cao, H; Zeng, M; Gan, Y; Zhou, Y


    Mechanical force-induced orthodontic root resorption is a major clinical challenge in orthodontic treatment. Macrophages play an important role in orthodontic root resorption, but the underlying mechanism remains unclear. In this study, we examined the mechanism by which the ratio of M1 to M2 macrophage polarization affects root resorption during orthodontic tooth movement. Root resorption occurred when nickel-titanium coil springs were applied on the upper first molars of rats for 3 to 14 d. Positively stained odontoclasts or osteoclasts with tartrate-resistant acid phosphatase were found in resorption areas. Meanwhile, M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) persistently accumulated on the compression side of periodontal tissues. In addition, the expressions of the M1 activator interferon-γ and the M1-associated pro-inflammatory cytokine tumor necrosis factor (TNF)-α were upregulated on the compression side of periodontal tissues. When the coil springs were removed at the 14th day after orthodontic force application, root resorption was partially rescued. The number of CD68(+)CD163(+) M2-like macrophages gradually increased on the compression side of periodontal tissues. The levels of M2 activator interleukin (IL)-4 and the M2-associated anti-inflammatory cytokine IL-10 also increased. Systemic injection of the TNF-α inhibitor etanercept or IL-4 attenuated the severity of root resorption and decreased the ratio of M1 to M2 macrophages. These data imply that the balance between M1 and M2 macrophages affects orthodontic root resorption. Root resorption was aggravated by an enhanced M1/M2 ratio but was partially rescued by a reduced M1/M2 ratio. © International & American Associations for Dental Research 2014.

  7. Striatal dopamine D1 and D2 receptors: widespread influences on methamphetamine-induced dopamine and serotonin neurotoxicity. (United States)

    Gross, Noah B; Duncker, Patrick C; Marshall, John F


    Methamphetamine (mAMPH) is an addictive psychostimulant drug that releases monoamines through nonexocytotic mechanisms. In animals, binge mAMPH dosing regimens deplete markers for monoamine nerve terminals, for example, dopamine and serotonin transporters (DAT and SERT), in striatum and cerebral cortex. Although the precise mechanism of mAMPH-induced damage to monoaminergic nerve terminals is uncertain, both dopamine D1 and D2 receptors are known to be important. Systemic administration of dopamine D1 or D2 receptor antagonists to rodents prevents mAMPH-induced damage to striatal dopamine nerve terminals. Because these studies employed systemic antagonist administration, the specific brain regions involved remain to be elucidated. The present study examined the contribution of dopamine D1 and D2 receptors in striatum to mAMPH-induced DAT and SERT neurotoxicities. In this experiment, either the dopamine D1 antagonist, SCH23390, or the dopamine D2 receptor antagonist, sulpiride, was intrastriatally infused during a binge mAMPH regimen. Striatal DAT and cortical, hippocampal, and amygdalar SERT were assessed as markers of mAMPH-induced neurotoxicity 1 week following binge mAMPH administration. Blockade of striatal dopamine D1 or D2 receptors during an otherwise neurotoxic binge mAMPH regimen produced widespread protection against mAMPH-induced striatal DAT loss and cortical, hippocampal, and amygdalar SERT loss. This study demonstrates that (1) dopamine D1 and D2 receptors in striatum, like nigral D1 receptors, are needed for mAMPH-induced striatal DAT reductions, (2) these same receptors are needed for mAMPH-induced SERT loss, and (3) these widespread influences of striatal dopamine receptor antagonists are likely attributable to circuits connecting basal ganglia to thalamus and cortex. Copyright © 2011 Wiley-Liss, Inc.

  8. Vitamin D(3) is more potent than vitamin D(2) in humans. (United States)

    Heaney, Robert P; Recker, Robert R; Grote, James; Horst, Ronald L; Armas, Laura A G


    Current unitage for the calciferols suggests that equimolar quantities of vitamins D(2) (D2) and D(3) (D3) are biologically equivalent. Published studies yield mixed results. The aim of the study was to compare the potencies of D2 and D3. The trial used a single-blind, randomized design in 33 healthy adults. Calciferols were dosed at 50,000 IU/wk for 12 wk. Principal outcome variables were area under the curve for incremental total 25-hydroxyvitamin D [25(OH)D] and change in calciferol content of sc fat. Incremental mean (sd) 25(OH)D area under the curve at 12 wk was 1366 ng · d/ml (516) for the D2-treated group and 2136 (606) for the D3 (P < 0.001). Mean (sd) steady-state 25(OH)D increments showed similar differences: 24 ng/ml for D2 (10.3) and 45 ng/ml (16.2) for D3 (P <0.001). Subcutaneous fat content of D2 rose by 50 μg/kg in the D2-treated group, and D3 content rose by 104 μg/kg in the D3-treated group. Total calciferol in fat rose by only 33 ng/kg in the D2-treated, whereas it rose by 104 μg/kg in the D3-treated group. Extrapolating to total body fat D3, storage amounted to just 17% of the administered dose. D3 is approximately 87% more potent in raising and maintaining serum 25(OH)D concentrations and produces 2- to 3-fold greater storage of vitamin D than does equimolar D2. For neither was there evidence of sequestration in fat, as had been postulated for doses in this range. Given its greater potency and lower cost, D3 should be the preferred treatment option when correcting vitamin D deficiency.

  9. Relationship between vitamin D-binding protein polymorphisms and blood vitamin D level in Korean patients with COPD

    Directory of Open Access Journals (Sweden)

    Park YM


    Full Text Available Youngmok Park,1 Young Sam Kim,1 Young Ae Kang,1 Ju Hye Shin,1 Yeon Mok Oh,2 Joon Beom Seo,3 Ji Ye Jung,1 Sang Do Lee2 On behalf of the KOLD study 1Division of Pulmonology, Department of Internal Medicine, Severance Hospital, Institute of Chest Diseases, Yonsei University College of Medicine, 2Department of Pulmonary and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, 3Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Background: In chronic obstructive pulmonary disease (COPD, the blood vitamin D3 level is generally low, and genetic polymorphisms of vitamin D-binding protein encoded by the GC gene are associated with COPD development. In this study, we examined the relationship between GC polymorphisms and plasma vitamin D3 level in Korean patients with COPD. Methods: The study included 175 COPD patients from the Korean Obstructive Lung Disease Cohort. Multivariate analysis was conducted with adjustment for age, body mass index (BMI, lung function, smoking status, smoking amount, and seasonal variation in blood vitamin D level. Vitamin D deficiency was defined as a plasma 25-hydroxyvitamin D3 level lower than 20 ng/mL. Results: The mean plasma vitamin D3 level was 17.5 ng/mL. The GC1F variant (44.3% and genotype 1F-2 (27.4% were the most common. The plasma vitamin D3 level was lower in patients with the GC2 variant (estimated =-3.73 ng/mL and higher in those with genotype 1F-1S (estimated =4.08 ng/mL. The GC2 variant was a significant risk factor for vitamin D deficiency (odds ratio =2.41. Among COPD clinical parameters, vitamin D deficiency was associated with a lower ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC regardless of GC polymorphisms. FEV1/FVC was higher in patients with genotype 1F-1F (estimated =3.61% and lower in those with genotype 1F-2 (estimated =-3.31%. The

  10. Consequences of daily corticosteroid dosing with or without pre-treatment with quinidine on the in vivo cytochrome P450 2D (CYP2D) enzyme in rats: effect on O-demethylation activity of dextromethorphan and expression levels of CYP2D1 mRNA. (United States)

    Giri, Poonam; Delvadia, Prashant; Gupta, Laxmikant; Patel, Nirmal; Trivedi, Priyal; Lad, Krishna; Patel, Hiren M; Srinivas, Nuggehally R


    1. Present investigation was carried out in rats to study influence of corticosteroids after repeated dosing with/without pre-treatment with CYP2D inhibitor quinidine on the CYP2D1 mRNA levels and CYP2D enzyme activity using dextromethorphan as probe substrate. 2. CYP2D1 mRNA was measured in liver homogenate using quantitative real-time polymerase chain reaction [qRT-PCR] and enzymatic reaction was studied ex vivo in liver S-9 fractions of rats treated with oral 10 mg/kg dexamethasone or prednisolone for five days or pre-treated with quinidine and followed by treatment with oral 10 mg/kg corticosteroids for five days. 3. Five days repeat dosing of dexamethasone or prednisolone decreased the activity of the rat liver CYP2D by 37% and 34%, at 30 min incubation and decreased CYP2D1 mRNA levels by 62% and 61%, respectively. 4. Pre-treatment of quinidine decreased the enzymatic activity of rat CYP2D by 58% and did not potentiate CYP2D inhibition by corticosteroids. This observation was further complemented by qRT-PCR data. 5. Corticosteroids caused CYP2D inhibition in rats vs. literature evidence of CYP2D induction in human hepatocytes/pregnant humans demonstrating lack of concordance. In vivo inhibition should be factored for interpretation of pharmacokinetic data of CYP2D substrates when treated with corticosteroids in rats.

  11. Disruption of dopamine D1/D2 receptor complex is involved in the function of haloperidol in cardiac H9c2 cells. (United States)

    Lencesova, L; Szadvari, I; Babula, P; Kubickova, J; Chovancova, B; Lopusna, K; Rezuchova, I; Novakova, Z; Krizanova, O; Novakova, M


    Haloperidol is an antipsychotic agent and acts as dopamine D2 receptor (D2R) antagonist, as a prototypical ligand of sigma1 receptors (Sig1R) and it increases expression of type 1 IP 3 receptors (IP 3 R1). However, precise mechanism of haloperidol action on cardiomyocytes through dopaminergic signaling was not described yet. This study investigated a role of dopamine receptors in haloperidol-induced increase in IP 3 R1 and Sig1R, and compared physiological effect of melperone and haloperidol on basic heart parameters in rats. We used differentiated NG-108 cells and H9c2 cells. Gene expression, Western blot and immunofluorescence were used to evaluate haloperidol-induced differences; proximity ligation assay (PLA) and immunoprecipitation to determine interactions of D1/D2 receptors. To evaluate cardiac parameters, Wistar albino male rats were used. We have shown that antagonism of D2R with either haloperidol or melperone results in upregulation of both, IP 3 R1 and Sig1R, which is associated with increased D2R, but reduced D1R expression. Immunofluorescence, immunoprecipitation and PLA support formation of heteromeric D1/D2 complexes in H9c2 cells. Treatment with haloperidol (but not melperone) caused decrease in systolic and diastolic blood pressure and significant increase in heart rate. Because D1R/D2R complexes can engage Gq-like signaling in other experimental systems, these results are consistent with the possibility that disruption of D1R/D2R complex in H9c2 cells might cause a decrease in IP 3 R1 activity, which in turn may account for the increase expression of IP 3 R and Sig1R. D2R is probably not responsible for changes in cardiac parameters, since melperone did not have any effect. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Waiting time distribution in M/D/1 queueing systems

    DEFF Research Database (Denmark)

    Iversen, Villy Bæk; Staalhagen, Lars


    The well-known formula for the waiting time distribution of M/D/1 queueing systems is numerically unsuitable when the load is close to 1.0 and/or the results for a large waiting time are required. An algorithm for any load and waiting time is presented, based on the state probabilities of M/D/1...

  13. Synaptic communication between neurons and NG2+ cells. (United States)

    Paukert, Martin; Bergles, Dwight E


    Chemical synaptic transmission provides the basis for much of the rapid signaling that occurs within neuronal networks. However, recent studies have provided compelling evidence that synapses are not used exclusively for communication between neurons. Physiological and anatomical studies indicate that a distinct class of glia known as NG2(+) cells also forms direct synaptic junctions with both glutamatergic and GABAergic neurons. Glutamatergic signaling can influence intracellular Ca(2+) levels in NG2(+) cells by activating Ca(2+) permeable AMPA receptors, and these inputs can be potentiated through high frequency stimulation. Although the significance of this highly differentiated form of communication remains to be established, these neuro-glia synapses might enable neurons to influence rapidly the behavior of this ubiquitous class of glial progenitors.

  14. Serum Vitamin D Levels Not Associated with Atopic Dermatitis Severity. (United States)

    Robl, Renata; Uber, Marjorie; Abagge, Kerstin Taniguchi; Lima, Monica Nunes; Carvalho, Vânia Oliveira


    The objective of the current study was to determine the relationship between serum vitamin D levels and the severity of atopic dermatitis (AD) in a Brazilian population. This was a cross-sectional study of patients younger than 14 years of age seen from April to November 2013. All patients fulfilled the Hanifin and Rajka Diagnostic Criteria for AD diagnosis. Disease severity was determined using the SCORing Atopic Dermatitis index and classified as mild (50). Serum vitamin D levels were classified as sufficient (≥30 ng/mL), insufficient (29-21 ng/mL), or deficient (≤20 ng/mL). A total of 105 patients met the inclusion criteria. Mild AD was diagnosed in 58 (55.2%) children, moderate in 24 (22.8%), and severe in 23 (21.9%). Vitamin D deficiency was observed in 45 individuals (42.9%). Of these, 24 (53.3%) had mild AD, 13 (28.9%) moderate, and 8 (17.7%) severe. Insufficient vitamin D levels were found in 45 (42.9%) individuals; 24 (53.3%) had mild AD, 9 (20.0%) moderate, and 12 (26.7%) severe. Of the 15 individuals (14.2%) with sufficient vitamin D levels, 10 (60.7%) had mild AD, 2 (13.3%) moderate, and 3 (20.0%) severe. The mean vitamin D level was 22.1 ± 7.3 ng/mL in individuals with mild AD, 20.8 ± 6.5 ng/mL in those with moderate AD, and 21.9 ± 9.3 ng/mL in those with severe AD. Variables such as sex, age, skin phototype, season of the year, and bacterial infection were not significantly associated with vitamin D levels. Levels of 25-hydroxyvitamin D were deficient or insufficient in 85% of the children, but serum vitamin D concentrations were not significantly related to AD severity. © 2016 Wiley Periodicals, Inc.

  15. Vitamin D Deficiency in Patients with Tuberculosis

    International Nuclear Information System (INIS)

    Iftikhar, R.; Kamran, S. M.; Haider, E.; Qadir, A.; Usman, H. B.


    Objective: To determine the frequency and association of Vitamin D deficiency in patients with tuberculosis. Study Design: Case control study. Place and Duration of Study: Medical Department, Combined Military Hospital, Kharian, from July 2010 to June 2012. Methodology: One hundred and five outdoor patients of tuberculosis were selected with 255 gender matched controls. Tuberculosis was diagnosed by presence of acid fast bacilli in sputum smears, positive culture for Mycobacterium tuberculosis or demonstration of chronic caseating granulomatous inflammation in tissue specimens. Controls were drawn randomly from general population. Serum 25 hydroxyvitamin D [25 (OH) D3] levels < 25 ng/ml was considered Vitamin D deficiency. The results were analyzed on SPSS version 17. Results: Mean Vitamin D levels were 23.23 A+- 6.81 ng/ml in cases, 29.27 A+- 8.89 ng/ml in controls (p < 0.0001). Vitamin D deficiency was found in 57% of cases and 33% controls (p < 0.0001). Mean Vitamin D levels were significantly lower in females with tuberculosis (20.84 ng/ml) as compared to males (25.03 ng/ml, p = 0.002). Mean BMI in patients of tuberculosis with Vitamin D deficiency were 19.51 A+- 1.77 kg/m2 and in patients with normal Vitamin D were 21.65 A+- 1.79 kg/m2 (p < 0.0001). Mean Vitamin D levels in patients with multi-drug resistant tuberculosis was lower to a mean of 15.41 A+- 4.67 ng/ml (p < 0.0001). Conclusion: There is significant deficiency of Vitamin D in patients with tuberculosis as compared to controls. This deficiency is more pronounced in females, individuals with low BMI, extra pulmonary and MDR tuberculosis. (author)

  16. Seasonal variation in vitamin D status of beef cattle reared in the central United States. (United States)

    Casas, E; Lippolis, J D; Kuehn, L A; Reinhardt, T A


    The objective was to retrospectively measure seasonal sunlight-associated variation in serum concentrations of 25-hydroxyvitamin D (25OHD) in beef cattle. The concentration of 25OHD was measured in crossbred animals born from March to May in 2011 and 2012. Vitamin D status 2 to 3 mo after birth (period 1) was only available for 2012 calves and was measured in June 2012. Period 1 animals had serum 25OHD concentrations of 26.3 ± 1.5 ng/mL. The 25OHD concentrations for late summer (period 2) were 46.6 ± 1.4 and 51.0 ± 1.5 ng/mL for 2011 and 2012, respectively. Serum concentration of 25OHD in early fall (period 3) were 63.8 ± 1.4 and 55.2 ± 1.5 ng/mL for calves in 2011 and 2012, respectively. Values observed for both late summer and early fall indicated vitamin D sufficiency (P vitamin D, the calves' midwinter (period 4) 25OHD concentrations fell to 15.2 ± 1.6 and 16.7 ± 1.5 ng/mL for 2011 and 2012, respectively, after 4 to 5 mo on a finishing diet (P vitamin D insufficiency in most species. Results indicate that calves are marginally sufficient to insufficient for vitamin D based on serum 25OHD concentrations soon after birth and during winter. Some individual animals would be classified vitamin D deficient. In the absence of sufficient UVB exposure, the dietary vitamin D requirements for rapidly growing beef cattle may need to be increased. Published by Elsevier Inc.

  17. Effects of dopamine D1-like and D2-like antagonists on cocaine discrimination in muscarinic receptor knockout mice. (United States)

    Thomsen, Morgane; Caine, Simon Barak


    Muscarinic and dopamine brain systems interact intimately, and muscarinic receptor ligands, like dopamine ligands, can modulate the reinforcing and discriminative stimulus (S(D)) effects of cocaine. To enlighten the dopamine/muscarinic interactions as they pertain to the S(D) effects of cocaine, we evaluated whether muscarinic M1, M2 or M4 receptors are necessary for dopamine D1 and/or D2 antagonist mediated modulation of the S(D) effects of cocaine. Knockout mice lacking M1, M2, or M4 receptors, as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg cocaine from saline in a food-reinforced drug discrimination procedure. Effects of pretreatments with the dopamine D1 antagonist SCH 23390 and the dopamine D2 antagonist eticlopride were evaluated. In intact mice, both SCH 23390 and eticlopride attenuated the cocaine discriminative stimulus effect, as expected. SCH 23390 similarly attenuated the cocaine discriminative stimulus effect in M1 knockout mice, but not in mice lacking M2 or M4 receptors. The effects of eticlopride were comparable in each knockout strain. These findings demonstrate differences in the way that D1 and D2 antagonists modulate the S(D) effects of cocaine, D1 modulation being at least partially dependent upon activity at the inhibitory M2/M4 muscarinic subtypes, while D2 modulation appeared independent of these systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Monoclonal antibody-based ELISA to quantify the major allergen of Cynodon dactylon (Bermuda grass) pollen, Cyn d 1. (United States)

    Duffort, O; Calabozo, B; González, R; Carpizo, J A; Barber, D; Polo, F


    Pollen of Bermuda grass (Cynodon dactylon) is an important cause of pollinosis in many areas of the world. Most patients show sensitivity to the major allergen Cyn d 1, a glycoprotein composed of a number of isoforms with a molecular mass of 31-32 kDa. The aim of this work was to develop a monoclonal antibody (mAb)-based ELISA to quantify Cyn d 1, and to assess the correlation of the allergen content with the biological activity of C. dactylon pollen extracts. After fusion of myeloma cells with spleen cells from a BALB/c mouse immunized with C. dactylon pollen extract, Cyn d 1-specific mAbs secreting hybridomas were selected, and the antibodies characterized. One of them (4.4.1) was used as the capture antibody in an ELISA method for Cyn d 1 quantitation. An anti-Cyn d 1 rabbit serum was used as the second antibody. Cyn d 1 was purified by immunoaffinity chromatography with mAb 4.4.1, characterized, and used as the standard in the assay. The identity, purity and isoallergen composition of affinity-purified Cyn d 1 was confirmed by N-terminal amino acid sequencing, SDS-PAGE, Western blot and 2D electrophoresis. The Cyn d 1 ELISA is highly specific and sensitive, with a detection limit of 0.24 ng/ml and a linear range of 1.1-9.2 ng/ml. An excellent correlation was found when the content of Cyn d 1, measured in 16 different extracts, was compared with the allergenic activity of the same extracts determined by RAST inhibition. The results prove the usefulness of the Cyn d 1 ELISA for the standardization of C. dactylon-allergen products on the basis of major allergen content. 2004 S. Karger AG, Basel.

  19. 1,25 (OH)2 vitamin D3-induced 45Ca uptake in vascular myocytes cultured from spontaneously hypertensive and normotensive rats

    International Nuclear Information System (INIS)

    Xue, Hong; McCarron, D.A.; Bukoski, R.D.


    The effect of 1,25 (OH) 2 vitamin D 3 on basal 45 Ca uptake was examined in vasvular smooth muscle cells cultured from mesenteric arteries of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) normotensive rats. Basal uptake of 45 Ca was significantly greater in myocytes of WKY than SHR at 5, 10, 30 and 60 min incubation with the isotope. Incubation with 1 ng/ml 1,25 (OH) 2 vitamin D 3 for 48 hr increased basal 45 Ca uptake between 1-10 min in SHR and between 5-10 min in WKY. The dose-response relationship indicated that cells from both strains are equally sensitive to the calciotropic effects of 1,25 (OH) 2 vitamin D 3 with half-maximal stimulation occurring at approximately 0.3-0.4 ng/ml. In cells of both strains maximal stimulation of 45 Ca uptake was achieved only after a 12-24 hr period of incubation with hormone and pretreatment with cycloheximide inhibited 1,24 (OH) 2 vitamin D 3 -enhanced 45 Ca uptake. Although 45 Ca binding by extracellular matrix material was significantly greater in WKY than SHR, 1,25 (OH) 2 vitamin D 3 had no effect on the amount of matrix 45 Ca binding in either strain

  20. Implication of Xenobiotic Metabolizing Enzyme gene (CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 Polymorphisms in Breast Carcinoma

    Directory of Open Access Journals (Sweden)

    Gabbouj Sallouha


    Full Text Available Abstract Background Xenobiotic Metabolizing Enzymes (XMEs contribute to the detoxification of numerous cancer therapy-induced products. This study investigated the susceptibility and prognostic implications of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene polymorphisms in breast carcinoma patients. Methods The authors used polymerase chain reaction and restriction enzyme digestion to characterize the variation of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene in a total of 560 unrelated subjects (246 controls and 314 patients. Results The mEH (C/C mutant and the NAT2 slow acetylator genotypes were significantly associated with breast carcinoma risk (p = 0.02; p = 0.01, respectively. For NAT2 the association was more pronounced among postmenopausal patients (p = 0.006. A significant association was found between CYP2D6 (G/G wild type and breast carcinoma risk only in postmenopausal patients (p = 0.04. Association studies of genetic markers with the rates of breast carcinoma specific overall survival (OVS and the disease-free survival (DFS revealed among all breast carcinoma patients no association to DFS but significant differences in OVS only with the mEH gene polymorphisms (p = 0.02. In addition, the mEH wild genotype showed a significant association with decreased OVS in patients with axillary lymph node-negative patients (p = 0.03 and with decreasesd DFS in patients with axillary lymph node-positive patients (p = 0.001. However, the NAT2 intermediate acetylator genotype was associated with decreased DFS in axillary lymph node-negative patients. Conclusion The present study may prove that polymorphisms of some XME genes may predict the onset of breast carcinoma as well as survival after treatment.

  1. M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Shoichi Fukui


    Full Text Available ObjectivesWe investigated the relationships among M1 monocytes, M2 monocytes, osteoclast (OC differentiation ability, and clinical characteristics in patients with rheumatoid arthritis (RA.MethodsPeripheral blood mononuclear cells (PBMCs were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate OC differentiation in vitro.ResultsForty RA patients and 20 healthy donors were included. Twenty-two patients (55% were anticitrullinated protein antibody (ACPA positive. The median M1/M2 ratio was 0.59 (0.31–1.11, interquartile range. There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated OC number in vitro in RA patients (ρ = 0.81, p < 0.001. The ACPA-positive patients had significantly higher M1/M2 ratios in vivo (p = 0.028 and significantly greater numbers of OCs in vitro (p = 0.005 than the ACPA-negative patients. Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to in vitro osteoclastogenesis. RA patients with M1/M2 ratios >1 (having relatively more M1 monocytes had higher C-reactive protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios ≤1. M1-dominant monocytes in vitro produced higher concentrations of interleukin-6 upon stimulation with lipopolysaccharide than M2 monocytes.ConclusionM1/M2 monocytes imbalance strongly contributes to osteoclastogenesis of RA patients. Our findings cast M1 and M2 monocyte subsets in a new light as a new target of treatments for RA to prevent progression of osteoclastic bone destruction.

  2. Minimal unitary representation of D(2,1;λ) and its SU(2) deformations and d=1, N=4 superconformal models

    International Nuclear Information System (INIS)

    Govil, Karan; Gunaydin, Murat


    Quantization of the geometric quasiconformal realizations of noncompact groups and supergroups leads directly to their minimal unitary representations (minreps). Using quasiconformal methods massless unitary supermultiplets of superconformal groups SU(2,2|N) and OSp(8 ⁎ |2n) in four and six dimensions were constructed as minreps and their U(1) and SU(2) deformations, respectively. In this paper we extend these results to SU(2) deformations of the minrep of N=4 superconformal algebra D(2,1;λ) in one dimension. We find that SU(2) deformations can be achieved using n pair of bosons and m pairs of fermions simultaneously. The generators of deformed minimal representations of D(2,1;λ) commute with the generators of a dual superalgebra OSp(2n ⁎ |2m) realized in terms of these bosons and fermions. We show that there exists a precise mapping between symmetry generators of N=4 superconformal models in harmonic superspace studied recently and minimal unitary supermultiplets of D(2,1;λ) deformed by a pair of bosons. This can be understood as a particular case of a general mapping between the spectra of quantum mechanical quaternionic Kähler sigma models with eight super symmetries and minreps of their isometry groups that descends from the precise mapping established between the 4d, N=2 sigma models coupled to supergravity and minreps of their isometry groups.

  3. Infinitely many N=1 dualities from m+1m=1

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Prarit; Intriligator, Kenneth; Song, Jaewon [Department of Physics, University of California,San Diego, La Jolla, CA 92093 (United States)


    We discuss two infinite classes of 4d supersymmetric theories, T{sub N}{sup (m)} and U{sub N}{sup (m)}, labelled by an arbitrary non-negative integer, m. The T{sub N}{sup (m)} theory arises from the 6d, A{sub N−1} type N=(2,0) theory reduced on a 3-punctured sphere, with normal bundle given by line bundles of degree (m+1,−m); the m=0 case is the N=2 supersymmetric T{sub N} theory. The novelty is the negative-degree line bundle. The U{sub N}{sup (m)} theories likewise arise from the 6d N=(2,0) theory on a 4-punctured sphere, and can be regarded as gluing together two (partially Higgsed) T{sub N}{sup (m)} theories. The T{sub N}{sup (m)} and U{sub N}{sup (m)} theories can be represented, in various duality frames, as quiver gauge theories, built from T{sub N} components via gauging and nilpotent Higgsing. We analyze the RG flow of the U{sub N}{sup (m)} theories, and find that, for all integer m>0, they end up at the same IR SCFT as SU(N) SQCD with 2N flavors and quartic superpotential. The U{sub N}{sup (m)} theories can thus be regarded as an infinite set of UV completions, dual to SQCD with N{sub f}=2N{sub c}. The U{sub N}{sup (m)} duals have different duality frame quiver representations, with 2m+1 gauge nodes.

  4. Association between vitamin d levels and adolescent idiopathic scoliosis

    Directory of Open Access Journals (Sweden)

    Rodrigo Martins Borges Ferreira Batista


    Full Text Available Objective: To compare the levels of 25-hydroxyvitamin D in patients with AIS and a control group. Methods: The patients were recruited from the outpatient clinic of our institution during the year of 2013. Children diagnosed with scoliosis before 10 or after 18 years of age, and those suffering from neurological or muscular disorders, congenital malformations or genetic syndromes were excluded. The 25-OHD levels were determined by a fully automated electrochemiluminescence test. The appropriate level of 25-OHD was defined as greater than 30 ng/mL. The results were compared to a group of healthy individuals. Results: In group 1 (control 63,3% showed abnormal vitamin D levels, while 91% of patients with AIS presented a low level of vitamin D. The mean BMI was 19.6 kg/m2 for controls and 20.3 kg/m2 for group 2. Statistical analysis showed significant difference (p<0.0001 between the levels of vitamin D. The average and minimum levels of vitamin D were respectively 27 and 13.6 ng/mL for group 1 and 18.8 and 3.13 ng/mL for AIS group. Conclusions: Patients with AIS had statistically significant lower levels of 25-OHD than healthy patients. Further research should be conducted to investigate the actual impact of serum vitamin D levels on the pathophysiology of AIS.

  5. Measurement of Aflatoxin M1 in Raw and Pasteurized Cow Milk Samples by HPLC

    Directory of Open Access Journals (Sweden)

    afshin Nazari


    Full Text Available Nazari A1, Noroozi H2, Movahedi M3, Khaksarian M1 1. Instructor, Department of Physiology, Faculty of Medicine, Lorestan University of Medical Sciences 2. Assistant Professor, Department of Mycology, Faculty of Medicine, Iran University of Medical Sciences 3. Assistant Professor, Department of Genetic Epidemiology, Faculty of Medicine, Lorestan University of Medical Sciences Abstract Background: Aflatoxin M1 is a hydroxylated form of aflatoxin B1 which is produced by Aspergillus flavus. This toxin is produced when cows or other ruminants eat foods contaminated with these mycotoxins and then excrete them in the milk. The toxin is a potent liver and kidney carcinogenetic agent. Materials and methods: Forty two raw cows milk samples from local sources of milk collection and forty samples of commercial pasteurized market milk from Khorramabad, Lorestan, Iran were collected in summer and winter season of 2005. Twenty-one cow milk samples and 20 pasteurized milk samples in each season were analyzed for the presence of aflatoxin M1 (AFM1 by HPLC immunoaffinity columns. Results: Four of 21 raw milk samples in summer showed AFM1 levels between 0.017-0.046 ng/ml and all samples (100% in winter showed the presence of AFM1 levels between 0.003-0.041ng/ ml. AFM1 was detected in 55% of market pasteurized cow milk samples ranging from 0.017 to 0.533 ng/ml in summer and 100% ranging from 0.005-0.0054 ng/ml in winter.,Only one of all milk samples of pasteurized milk in summer had toxin level (0.533 ng/ml more than the maximum permissive limit (0.5 ng/ml. No significant difference was observed among mean contamination level of raw and pasteurized cow milk in two seasons. Key words: Aflatoxin M1, raw milk, pasteurized milk, Khoramabad, HPLC

  6. Low percentage of free prostate-specific antigen (PSA) is a strong predictor of later detection of prostate cancer among Japanese men with serum levels of total PSA of 4.0 ng/mL or less. (United States)

    Sasaki, Mitsuharu; Ishidoya, Shigeto; Ito, Akihiro; Saito, Hideo; Yamada, Shigeyuki; Mitsuzuka, Koji; Kaiho, Yasuhiro; Shibuya, Daisuke; Yamaguchi, Takuhiro; Arai, Yoichi


    To investigate the effect of the percentage of free prostate-specific antigen (%fPSA) on future prostate cancer risk. We examined serum total PSA (tPSA) and %fPSA annually in a prostate cancer-screening cohort between July 2001 and June 2011. Men with tPSA >4.0 ng/mL or tPSA of 2.0-4.0 ng/mL with %fPSA ≤12% were screened as positive and were recommended to undergo a biopsy. The study population consisted of 6368 men, aged 40-79 years, who had tPSA ≤4.0 ng/mL at initial screening and who subsequently underwent 1 or more screenings. We calculated the cumulative risk and hazard ratio of prostate cancer stratified by the initial %fPSA groups as quartiles of prostate cancer patients. During a median follow-up of 36 months, 119 men were diagnosed with prostate cancer. The lowest quartile of %fPSA (22.2%). For the subset with an initial tPSA ≤1.0 ng/mL, all men diagnosed with cancer had an initial %fPSA ≤33.3% (median). For the subset with tPSA >1.0 ng/mL, men with %fPSA ≤23.0% (median) had significantly higher risk for cancer than those with %fPSA >23.0% (P men with prostate cancer in whom pathologic findings were available, 79 (69.3%) had a Gleason score ≥3 + 4 = 7. A low %fPSA is a strong predictor of a subsequent diagnosis of prostate cancer among men with tPSA levels ≤4.0 ng/mL. Measurement of %fPSA might enhance the detection of high-grade cancer that warrants aggressive treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor M1, M2, and M4 receptor knockout mice. (United States)

    Joseph, Lauren; Thomsen, Morgane


    Muscarinic M 1 /M 4 receptor stimulation can reduce abuse-related effects of cocaine and may represent avenues for treating cocaine addiction. Muscarinic antagonists can mimic and enhance effects of cocaine, including discriminative stimulus (S D ) effects, but the receptor subtypes mediating those effects are not known. A better understanding of the complex cocaine/muscarinic interactions is needed to evaluate and develop potential muscarinic-based medications. Here, knockout mice lacking M 1 , M 2 , or M 4 receptors (M 1 -/- , M 2 -/- , M 4 -/- ), as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg cocaine from saline. Muscarinic receptor antagonists with no subtype selectivity (scopolamine), or preferential affinity at the M 1 , M 2 , or M 4 subtype (telenzepine, trihexyphenidyl; methoctramine, AQ-RA 741; tropicamide) were tested alone and in combination with cocaine. In intact animals, antagonists with high affinity at M 1 /M 4 receptors partially substituted for cocaine and increased the S D effect of cocaine, while M 2 -preferring antagonists did not substitute, and reduced the S D effect of cocaine. The cocaine-like effects of scopolamine were absent in M 1 -/- mice. The cocaine S D attenuating effects of methoctramine were absent in M 2 -/- mice and almost absent in M 1 -/- mice. The findings indicate that the cocaine-like S D effects of muscarinic antagonists are primarily mediated through M 1 receptors, with a minor contribution of M 4 receptors. The data also support our previous findings that stimulation of M 1 receptors and M 4 receptors can each attenuate the S D effect of cocaine, and show that this can also be achieved by blocking M 2 autoreceptors, likely via increased acetylcholine release. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Experimental Conditions: SE24_S1_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available rometry with 13C‑Labeling for Chemical Assignment of Sulfur-Containing Metabolites ...SE24_S1_M1_D1 SE24 Combination of Liquid Chromatography-Fourier Transform Ion Cyclotron Resonance-Mass Spect

  9. Nano-level determination of copper with atomic absorption spectrometry after pre-concentration on N,N-(4-methyl-1,2-phenylene)diquinoline-2-carboxamide-naphthalene

    Energy Technology Data Exchange (ETDEWEB)

    Rezaei, Behzad, E-mail: [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Sadeghi, Elham; Meghdadi, Soraia [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of)


    A novel, simple, sensitive and effective method has been developed for selective extraction and pre-concentration of copper on N,N-(4-methyl-1,2-phenylene)diquinoline-2-carboxamide-naphthalene. After pre-concentration, copper was eluted from sorbent with hydrochloric acid, and then flame atomic absorption spectrometry (FAAS) was used for its determination. The effect of pH, sample flow rate and the volume and concentration of eluent on the recovery of the analyte was investigated and the optimum conditions were established. A pre-concentration factor of 400, and an adsorption capacity of 6.9 mg g{sup -1} of the solid-phase sorbent or 82.8 mg g{sup -1} of ligand was achieved using the optimum conditions. The calibration graph was linear in the range of 1.0-4000 ng mL{sup -1} with the detection limit of 1.0 ng mL{sup -1}. A R.S.D. value of 2.4% was obtained by this method for 400 ng mL{sup -1} of Cu{sup 2+} solution. This procedure has been successfully applied to separate and determine the ultra trace levels of copper in the environmental samples, free from the interference of some diverse ions.

  10. Tritiated-water detection with a 2D(γ,n)1H monitor

    International Nuclear Information System (INIS)

    Winn, W.G.; Baumann, N.P.

    Tritiated process water is monitored by detecting the D 2 O component via the 2 D(γ,n) 1 H reaction. A probe containing a 1 to 7 mCi 24 Na (15 h) γ-source and six 3 He neutron detectors produces and monitors the 2 D(γ,n) 1 H reaction. A variety of probe configurations were examined for D 2 O detection sensitivity. The corresponding detection limits range from 6 to 280 μL for D 2 O droplets and 1 to 13 μL/cm for D 2 O streams, when 10-minute neutron counting with a 1 mCi γ-source is used. Results from two field applications illustrate the utility of the monitor

  11. Nature of the bonding in the AuNgX (Ng = Ar, Kr, Xe; X = F, Cl, Br, I) molecules. Topological study on electron density and the electron localization function (ELF). (United States)

    Makarewicz, Emilia; Gordon, Agnieszka J; Berski, Slawomir


    Topological analysis of the electron localization function (ELF) has been carried out for the AuNgX (Ng = Ar, Kr, Xe; X = F, Cl, Br, I) molecules using the wave function approximated by the CCSD, MP2, and DFT(B3LYP, M062X) methods including zero-order regular approximation (ZORA). In the Ng-F bond, the bonding disynaptic attractor V(Ng,F) is missing; therefore, there are no signs of the covalent binding. The nature of the Au-Ng bond depends on the computational method used. Analysis of the ELF carried out for the AuArF and AuXeF molecules, with the wave function approximated by the CCSD and MP2 methods, shows the V(Au,Ng) attractor possibly corresponding to a partially covalent binding between the gold and noble gas atom. However, its very small basin population (<1e) and a very large value of the variance of the basin population suggest that the Au-Ng bond has a very delocalized character. Such bond nature may be related to the charge shift concept with a resonance of the Au(-+)NgX, Au(+-)NgX hybrids. The weakest Au-Ng bond, in terms of the smallest amount of electron density for the V(Au,Ng) basin, is found for the AuKrF molecule with the CCSD method (0.13e). The MP2 method, however, does not yield any V(Au, Ng) population; hence, the covalent Au-Kr bond is not confirmed. Because the V(Au,Ng) attractor is also not observed with the DFT method, the proper characterization of the Au-Ng bond requires proper description of correlation effects. Additional studies on the Au2 and [AuXe](+) molecules, performed at the CCSD and B3LYP levels, exhibit no V(Au,Au) and V(Au,Xe) bonding basins either.

  12. Photoionization cross-section of thallium 7 2D5/2 state at 1.06 μm radiation

    International Nuclear Information System (INIS)

    Ko, Kwang Hoon; Jeong, Do Young; Lim, Gwon; Kim, Jae Woo; Kim, Taek Soo; Rho, Si Pyo; Kim, Cheol Jung


    Thallium has two naturally occurring isotopes of T1-203 and T1-205, which have abundances of 30% and 70%, respectively. Development of the isotope separation technique of T1-203 has been attractive due to its industrial demand. T1-203 is raw material for production of T1-201 radioisotopes by proton bombardment in a cyclotron. The final product of 2 01 'T1C1 radiopharmaceuticals is widely used to diagnose heart disease. Electric field ionization has been proposed for isotope selective ionization of thallium atoms but it is not adequate to produce massive thallium ions. We report the result of infra-red (IR) photoionization experiment of thallium atoms. The measures photoionization cross-section of 7 2 D 5/2 state of atoms was at 1.06 μm radiation, which means that ionization efficiency higher than 80% can be achieved with a pulsed Nd:YAG laser of pulse energy density of about. For the accurate determination of the photoionization cross-section, calibration of the linearity of a energy meter should be performed. Density matrix equations were employed for the simulation of the photoionization process and its results were used to determine the photoionization cross-section.

  13. 25-Hydroxyvitamin D (25(OH)D) and biomarkers of ovarian reserve. (United States)

    Jukic, Anne Marie Z; Baird, Donna D; Wilcox, Allen J; Weinberg, Clarice R; Steiner, Anne Z


    The aim of the study was to examine the associations between 25-hydroxyvitamin D (25(OH)D) and biomarkers of ovarian reserve in a large community-based sample of women. In 2010 to 2016, women aged 30 to 44 years without any known fertility problems were recruited from the Chapel Hill, NC area for a prospective time-to-pregnancy cohort study. At enrollment 561 women provided a blood sample that was used to measure 25(OH)D, anti-Müllerian hormone (AMH), follicle-stimulating hormone, and inhibin-B. Unadjusted associations were estimated with Spearman correlation coefficients. Multivariable linear regression was used to estimate associations of 25(OH)D with ovarian reserve biomarkers, after adjusting for age, race, body mass index, smoking history, and recent use of hormonal birth control. The mean 25(OH)D was 36 ng/mL (SD = 11 ng/mL). 25(OH)D was not correlated with AMH, follicle-stimulating hormone, or inhibin-B (all r < 0.03). Multivariable results with continuous hormonal outcomes were also null. For dichotomous outcomes, there was a tendency for insufficient 25(OH)D (<30 ng/mL) to be associated with low AMH (<0.7 ng/mL) (odds ratio [95% CI]: 1.8 [0.9-4]). For the most part, 25(OH)D was not associated with ovarian reserve biomarkers in a group of women trying to become pregnant. We found some evidence that low 25(OH)D (<30 ng/mL) was associated with low AMH, but this should be confirmed in studies with a higher prevalence of low 25(OH)D.

  14. 25-Hydroxyvitamin D response to graded vitamin D₃ supplementation among obese adults. (United States)

    Drincic, Andjela; Fuller, Eileen; Heaney, Robert P; Armas, Laura A G


    Guidelines have suggested that obese adults need 2 to 3 times more vitamin D than lean adults to treat vitamin D deficiency, but few studies have evaluated the vitamin D dose response in obese subjects. The purpose of this study was to characterize the pharmacokinetics of 25-hydroxyvitamin D [25(OH)D] response to 3 different doses of vitamin D₃ (cholecalciferol) in a group of obese subjects and to quantify the 25(OH)D dose-response relationship. DESIGN, SETTING, INTERVENTION, PATIENTS: This was a randomized, single-blind study of 3 doses of oral vitamin D₃ (1000, 5000, or 10,000 IU) given daily to 67 obese subjects for 21 weeks during the winter months. Serum 25(OH)D levels were measured at baseline and after vitamin D replacement, and 25(OH)D pharmacokinetic parameters were determined, fitting the 25(OH)D concentrations to an exponential model. Mean measured increments in 25(OH)D at week 21 were 12.4 ± 9.7 ng/mL in the 1000 IU/d group, 27.8 ± 10.2 ng/mL in the 5000 IU/d group, and 48.1 ± 19.6 ng/mL in the 10,000 IU/d group. Steady-state increments computed from the model were 20.6 ± 17.1, 35.2 ± 14.6, and 51.3 ± 22.0 ng/mL, respectively. There were no hypercalcuria or hypercalcemia events during the study. Our data show that in obese people, the 25(OH)D response to vitamin D₃ is directly related to dose and body size with ∼2.5 IU/kg required for every unit increment in 25(OH)D (nanograms per milliliter).

  15. Axonal degeneration stimulates the formation of NG2+ cells and oligodendrocytes in the mouse

    DEFF Research Database (Denmark)

    Nielsen, Helle Hvilsted; Ladeby, Rune; Drøjdahl, Nina


    the response of the NG2+ cells to the different components of demyelinating pathology, we investigated the response of adult NG2+ cells to axonal degeneration in the absence of primary myelin or oligodendrocyte pathology. Axonal degeneration was induced in the hippocampal dentate gyrus of adult mice...... by transection of the entorhino-dentate perforant path projection. The acutely induced degeneration of axons and terminals resulted in a prompt response of NG2+ cells, consisting of morphological transformation, cellular proliferation, and upregulation of NG2 expression days 2-3 after surgery. This was followed...

  16. Protein kinase D stabilizes aldosterone-induced ERK1/2 MAP kinase activation in M1 renal cortical collecting duct cells to promote cell proliferation.

    LENUS (Irish Health Repository)

    McEneaney, Victoria


    Aldosterone elicits transcriptional responses in target tissues and also rapidly stimulates the activation of protein kinase signalling cascades independently of de novo protein synthesis. Here we investigated aldosterone-induced cell proliferation and extra-cellular regulated kinase 1 and 2 (ERK1\\/2) mitogen activated protein (MAP) kinase signalling in the M1 cortical collecting duct cell line (M1-CCD). Aldosterone promoted the proliferative growth of M1-CCD cells, an effect that was protein kinase D1 (PKD1), PKCdelta and ERK1\\/2-dependent. Aldosterone induced the rapid activation of ERK1\\/2 with peaks of activation at 2 and 10 to 30 min after hormone treatment followed by sustained activation lasting beyond 120 min. M1-CCD cells suppressed in PKD1 expression exhibited only the early, transient peaks in ERK1\\/2 activation without the sustained phase. Aldosterone stimulated the physical association of PKD1 with ERK1\\/2 within 2 min of treatment. The mineralocorticoid receptor (MR) antagonist RU28318 inhibited the early and late phases of aldosterone-induced ERK1\\/2 activation, and also aldosterone-induced proliferative cell growth. Aldosterone induced the sub-cellular redistribution of ERK1\\/2 to the nuclei at 2 min and to cytoplasmic sites, proximal to the nuclei after 30 min. This sub-cellular distribution of ERK1\\/2 was inhibited in cells suppressed in the expression of PKD1.

  17. NG2/CSPG4 and progranulin in the posttraumatic glial scar. (United States)

    Schäfer, Michael K E; Tegeder, Irmgard


    Traumatic injury of the central nervous system is one of the leading causes of death and disability in young adults. Failure of regeneration is caused by autonomous neuronal obstacles and by formation of the glial scar, which is essential to seal the injury but also constitutes a barrier for regrowing axons. The scar center is highly inflammatory and populated by NG2+ glia, whereas astrocytes form the sealing border and trap regrowing axons, suggesting that the non-permissive environment of activated astrocytes and extracellular matrix components is one of the reasons for the regenerative failure. Particularly, secreted chondroitin-sulfate proteoglycans, CSPGs, of the lectican family hinder axonal regrowth. In contrast, the transmembrane CSPG, NG2/CSPG4, appears to be functionally closer related to axon growth permissive heparan sulfate proteoglycans, HSPGs, and synaptic adhesion molecules, which all regulate synaptic signaling and plasticity upon alpha-secretase mediated shedding. Consequently, knockout of NG2/CSPG4 aggravates tissue loss, inflammation and neurologic deficits after brain injury, a phenotype partly mimicked by deletion of HSPG-binding proteins such as the HSPG2/perlecan-interacting protein, progranulin that is also a functional ligand of Notch and Eph2a. Indeed, structural features or progranulin's targets and NG2 may point to direct reciprocal regulations that may act in concert to overcome injury-evoked inflammation and neuronal dystrophy. This review provides an overview of the pathophysiology of the glial scar after brain injury, with a specific focus on NG2/CSPG4, its functions before and after shedding and putative reciprocal influences with the glycoprotein progranulin. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 2,4-D and Glyphosate affect aquatic biofilm accrual, gross primary production, and community respiration

    Directory of Open Access Journals (Sweden)

    Lawton E. Shaw


    Full Text Available 2,4-Dichlorophenoxyacetic acid (2,4-D and glyphosate are widely used agricultural herbicides commonly found in surface waters near cultivated land. Field experiments were conducted to determine the effects of 2,4-D and glyphosate on biofilms in a pond next to agricultural land in Athabasca, Alberta. Contaminant-exposure substrates (CES consisted of GF/C glass fiber or a cellulose filter paper substrates placed on specimen jars filled with agar that contained low levels of nitrogen and phosphorus, and different concentrations (15, 9.0, 1.5 mM of either 2,4-D or glyphosate. Nutrients and herbicide diffused freely through the agar to the substrate surface. CES arrays were deployed 15 cm below the water surface for 22 days, after which biofilms were collected and biomass (chlorophyll a, autotroph gross primary production (GPP, and heterotroph community respiration (CR were measured. 2,4-D (15 mM caused significant decreases in rates of biomass accrual (−22%, GPP (−34%, and CR(−63%. Glyphosate (15 mM also caused significant decreases in rates of biomass accrual (−50%, GPP (−67%, and CR (−47%. For the contaminant concentrations used, mean flux rates are estimated to be between 50–700 ng cm−2 min−1.

  19. Renal imaging with a new agent sup(99m)Tc-d1-DMS

    International Nuclear Information System (INIS)

    Tanaka, A.


    By using sup(99m)-Tc-d1 DMS labeled with 99 m-Tc using stannous chloride and prepared with freeze-dried d1-DMS containing a 3:1 molar ratio of DMS and Sn +2 the effect of stereochemical factor of DMS on kidney affinity, renal images, blood clearance, urinary excretion was studied in experimental animals and two normal volunteers and 75 patients. The comparation revealed a quite similar formation of complex II from d1-DMS to that from the meso-form, judge from its absorption spectra and absorption behavior into the gel. The stereochemical difference of DMS is not a critical factor for the formation of the sup(99m)-Tc-DMS complex with high affinity for the kidney, although it is believed that the renal accumulation of Tc-complex will depend greatly on chemical configuration of the complex. (APR)

  20. Defining the appropriate radiation dose for pretreatment PSA no. <=no. 10 ng/mL prostate cancer

    International Nuclear Information System (INIS)

    Pinover, Wayne H.; Hanlon, Alexandra L.; Horwitz, Eric M.; Hanks, Gerald E.


    Purpose: To investigate whether a dose response exists for biochemical no evidence of disease (bNED) control in prostate cancer patients with pretreatment prostate-specific antigen (PSA) no. =no. 7600 cGy. Median dose in these three groups was 7067 cGy, 7278 cGy, and 7734 cGy, respectively. Univariate analysis was performed to determine differences in bNED control (American Society for Therapeutic Radiology and Oncology [ASTRO] Consensus Guidelines definition of failure) by dose group for the entire cohort, for 310 good prognosis patients (T1-T2A, Gleason score 2-6, absence of PNI), and for 178 poor prognosis patients (T2B-T3 or Gleason score 7-10 or presence of PNI) . Multivariate analysis (MVA) was performed to determine if dose was an independent predictor of bNED control. Median follow-up was 36 months. Results: A dose response was not demonstrated for the entire group of patients with pretreatment PSA no. =no. 7600 cGy were associated with 5-year bNED control rates of 73%, 86%, and 89%, respectively (p = 0.12). MVA demonstrated prognosis group (p = 0.038) to be the only independent predictor of bNED control. Good prognosis patients had a 5-year bNED of 85% and no dose response was seen. The subgroup of poor prognosis patients demonstrated a 5-year bNED control rate of 81% and a dose response was seen for those receiving no. >=no. 7600 cGy, compared to the two lower dose groups (94% vs. 75% vs. 70%; p = 0.0062). MVA for the poor prognosis subset demonstrated dose (p = 0.01) to be the only independent predictor for improved bNED control. Conclusions: The poor prognosis subset of PSA no. <=no. 10 ng/mL prostate cancer patients benefit from dose escalation. A dose response is not demonstrated for prostate cancer patients with pretreatment PSA no. <=no. 10 ng/mL and other favorable features

  1. The vitamin D analogue ED71 but Not 1,25(OH2D3 targets HIF1α protein in osteoclasts.

    Directory of Open Access Journals (Sweden)

    Yuiko Sato

    Full Text Available Although both an active form of the vitamin D metabolite, 1,25(OH2D3, and the vitamin D analogue, ED71 have been used to treat osteoporosis, anti-bone resorbing activity is reportedly seen only in ED71- but not in 1,25(OH2D3 -treated patients. In addition, how ED71 inhibits osteoclast activity in patients has not been fully characterized. Recently, HIF1α expression in osteoclasts was demonstrated to be required for development of post-menopausal osteoporosis. Here we show that ED71 but not 1,25(OH2D3, suppress HIF1α protein expression in osteoclasts in vitro. We found that 1,25(OH2D3 or ED71 function in osteoclasts requires the vitamin D receptor (VDR. ED71 was significantly less effective in inhibiting M-CSF and RANKL-stimulated osteoclastogenesis than was 1,25(OH2D3 in vitro. Downregulation of c-Fos protein and induction of Ifnβ mRNA in osteoclasts, both of which reportedly block osteoclastogenesis induced by 1,25(OH2D3 in vitro, were both significantly higher following treatment with 1,25(OH2D3 than with ED71. Thus, suppression of HIF1α protein activity in osteoclasts in vitro, which is more efficiently achieved by ED71 rather than by 1,25(OH2D3, could be a reliable read-out in either developing or screening reagents targeting osteoporosis.

  2. Dipole model analysis of F2cc¯${m{F}}_2^{{m{car c}}} $ derived from the new D* data in DIS at HERA

    Directory of Open Access Journals (Sweden)

    Luszczak Agnieszka


    Full Text Available I analyse the new D* deep inelastic scattering data from HERA with the help of dipole models. I calculate F2cc¯${m{F}}_2^{{m{car c}}} $ from the GBW [1] and BGK [2] saturation models. I compare results with the last values determined by H1 at low Q2. I find good agreement with the data.

  3. Vitamin D Deficiency Among Professional Basketball Players. (United States)

    Fishman, Matthew P; Lombardo, Stephen J; Kharrazi, F Daniel


    Vitamin D plays an important role in several systems of the human body. Various studies have linked vitamin D deficiency to stress and insufficiency fractures, muscle recovery and function, and athletic performance. The prevalence of vitamin D deficiency in the elite athletic population has not been extensively studied, and very few reports exist among professional athletes. There is a high prevalence of vitamin D deficiency or insufficiency among players attending the National Basketball Association (NBA) Combine. Cross-sectional study; Level of evidence, 3. This is a retrospective review of data previously collected as part of the routine medical evaluation of players in the NBA Combines from 2009 through 2013. Player parameters evaluated were height, weight, body mass index (BMI), and vitamin D level. Statistical analysis using t tests and analysis of variance was used to detect any correlation between the player parameters and vitamin D level. Vitamin D levels were categorized as deficient (32 ng/mL). After institutional review board approval was submitted to the NBA, the NBA released deidentified data on 279 players who participated in the combines from 2009 through 2013. There were 90 players (32.3%) who were deficient, 131 players (47.0%) who were insufficient, and 58 players (20.8%) who were sufficient. A total of 221 players (79.3%) were either vitamin D deficient or insufficient. Among all players included, the average vitamin D level was 25.6 ± 10.2 ng/mL. Among the players who were deficient, insufficient, and sufficient, the average vitamin D levels were 16.1 ± 2.1 ng/mL, 25.0 ± 3.4 ng/mL, and 41.6 ± 8.6 ng/mL, respectively. Player height and weight were significantly increased in vitamin D-sufficient players compared with players who were not sufficient (P = .0008 and .009, respectively). Player age and BMI did not significantly differ depending on vitamin D status (P = .15 and .77, respectively). There is a high prevalence of vitamin D deficiency

  4. An N=1 superfield action for M2 branes

    International Nuclear Information System (INIS)

    Mauri, Andrea; Petkou, Anastasios C.


    We present an octonionic N=1 superfield action that reproduces in components the action of Bagger and Lambert for M2 branes. By giving an expectation value to one of the scalars we obtain the maximally supersymmetric superfield action for D2 branes

  5. 2D molybdenum disulphide (2D-MoS2) modified electrodes explored towards the oxygen reduction reaction (United States)

    Rowley-Neale, Samuel J.; Fearn, Jamie M.; Brownson, Dale A. C.; Smith, Graham C.; Ji, Xiaobo; Banks, Craig E.


    Two-dimensional molybdenum disulphide nanosheets (2D-MoS2) have proven to be an effective electrocatalyst, with particular attention being focused on their use towards increasing the efficiency of the reactions associated with hydrogen fuel cells. Whilst the majority of research has focused on the Hydrogen Evolution Reaction (HER), herein we explore the use of 2D-MoS2 as a potential electrocatalyst for the much less researched Oxygen Reduction Reaction (ORR). We stray from literature conventions and perform experiments in 0.1 M H2SO4 acidic electrolyte for the first time, evaluating the electrochemical performance of the ORR with 2D-MoS2 electrically wired/immobilised upon several carbon based electrodes (namely; Boron Doped Diamond (BDD), Edge Plane Pyrolytic Graphite (EPPG), Glassy Carbon (GC) and Screen-Printed Electrodes (SPE)) whilst exploring a range of 2D-MoS2 coverages/masses. Consequently, the findings of this study are highly applicable to real world fuel cell applications. We show that significant improvements in ORR activity can be achieved through the careful selection of the underlying/supporting carbon materials that electrically wire the 2D-MoS2 and utilisation of an optimal mass of 2D-MoS2. The ORR onset is observed to be reduced to ca. +0.10 V for EPPG, GC and SPEs at 2D-MoS2 (1524 ng cm-2 modification), which is far closer to Pt at +0.46 V compared to bare/unmodified EPPG, GC and SPE counterparts. This report is the first to demonstrate such beneficial electrochemical responses in acidic conditions using a 2D-MoS2 based electrocatalyst material on a carbon-based substrate (SPEs in this case). Investigation of the beneficial reaction mechanism reveals the ORR to occur via a 4 electron process in specific conditions; elsewhere a 2 electron process is observed. This work offers valuable insights for those wishing to design, fabricate and/or electrochemically test 2D-nanosheet materials towards the ORR.Two-dimensional molybdenum disulphide nanosheets

  6. Vitamin D supplementation in pregnancy, prenatal 25(OH)D levels, race, and subsequent asthma or recurrent wheeze in offspring: Secondary analyses from the Vitamin D Antenatal Asthma Reduction Trial. (United States)

    Wolsk, Helene M; Harshfield, Benjamin J; Laranjo, Nancy; Carey, Vincent J; O'Connor, George; Sandel, Megan; Strunk, Robert C; Bacharier, Leonard B; Zeiger, Robert S; Schatz, Michael; Hollis, Bruce W; Weiss, Scott T; Litonjua, Augusto A


    Nutrient trials differ from drug trials because participants have varying circulating levels at entry into the trial. We sought to study the effect of a vitamin D intervention in pregnancy between subjects of different races and the association between 25-hydroxyvitamin D 3 (25[OH]D) levels in pregnancy and the risk of asthma/recurrent wheeze in offspring. The Vitamin D Antenatal Asthma Reduction Trial is a randomized trial of pregnant women at risk of having children with asthma randomized to 4400 international units/d vitamin D or placebo plus 400 international units/d vitamin D. Asthma and recurrent wheezing until age 3 years were recorded. African American (AA) women (n = 312) had lower initial levels of 25(OH)D (mean [SD], 17.6 ng/mL [8.3 ng/mL]) compared with non-AA women (n = 400; 27.1 ng/mL [9.7 ng/mL], P asthma/recurrent wheezing in offspring (P for interaction = .77). Having an initial level of greater than 30 ng/mL and being randomized to the intervention group was associated with the lowest risk for asthma/recurrent wheeze by age 3 years compared with having an initial level of less than 20 ng/mL and receiving placebo (adjusted odds ratio, 0.42; 95% CI, 0.19-0.91). We did not find differences between AA and non-AA mothers in the effect of maternal vitamin D supplementation and asthma/recurrent wheeze in offspring at 3 years. Maternal supplementation of vitamin D, particularly in mothers with initial 25(OH)D levels of greater than 30 ng/mL, reduced asthma/recurrent wheeze in the offspring through age 3 years, suggesting that higher vitamin D status beginning in early pregnancy is necessary for asthma/recurrent wheeze prevention in early life. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  7. 1D ferromagnetic edge contacts to 2D graphene/h-BN heterostructures (United States)

    Karpiak, Bogdan; Dankert, André; Cummings, Aron W.; Power, Stephen R.; Roche, Stephan; Dash, Saroj P.


    We report the fabrication of one-dimensional (1D) ferromagnetic edge contacts to two-dimensional (2D) graphene/h-BN heterostructures. While aiming to study spin injection/detection with 1D edge contacts, a spurious magnetoresistance signal was observed, which is found to originate from the local Hall effect in graphene due to fringe fields from ferromagnetic edge contacts and in the presence of charge current spreading in the nonlocal measurement configuration. Such behavior has been confirmed by the absence of a Hanle signal and gate-dependent magnetoresistance measurements that reveal a change in sign of the signal for the electron- and hole-doped regimes, which is in contrast to the expected behavior of the spin signal. Calculations show that the contact-induced fringe fields are typically on the order of hundreds of mT, but can be reduced below 100 mT with careful optimization of the contact geometry. There may be an additional contribution from magnetoresistance effects due to tunneling anisotropy in the contacts, which needs further investigation. These studies are useful for optimization of spin injection and detection in 2D material heterostructures through 1D edge contacts.

  8. Modifiable determinants of serum 25-hydroxyvitamin D status in early childhood: opportunities for prevention. (United States)

    Maguire, Jonathon L; Birken, Catherine S; Khovratovich, Marina; Degroot, Julie; Carsley, Sarah; Thorpe, Kevin E; Mamdani, Muhammad; Parkin, Patricia C


    OBJECTIVES To determine the effect of modifiable dietary intake variables (current vitamin D supplementation and daily cow's milk intake) on 25-hydroxyvitamin D level in early childhood and to evaluate the relationship between these modifiable dietary factors and other largely nonmodifiable determinants of vitamin D status including skin pigmentation and season. DESIGN Cross-sectional study. SETTING Primary care pediatric and family medicine practices participating in the TARGet Kids! practice-based research network in Toronto, Ontario, Canada. PARTICIPANTS From December 2008 to June 2011, healthy children 1 to 5 years of age were recruited during a routine physician's visit. INTERVENTIONS Survey, anthropometric measurements, and laboratory data were collected. A multivariable linear regression model was developed to examine the independent effects of vitamin D supplementation and daily volume of cow's milk on 25-hydroxyvitamin D level. MAIN OUTCOME MEASURES 25-Hydroxyvitamin D level. RESULTS Blood was obtained in 1898 children. Two modifiable dietary intake variables, vitamin D supplementation and cow's milk, increased 25-hydroxyvitamin D level by 3.4 ng/mL (95% CI, 2-4 ng/mL) and 1.6 ng/mL per 250-mL cup per day (95% CI, 1-2 ng/mL), respectively. Two nonmodifiable variables reflecting cutaneous vitamin D synthesis (skin pigmentation and season) were also strongly associated with 25-hydroxyvitamin D status but accounted for a much smaller proportion of the explained variation in 25-hydroxyvitamin D level. The effect of vitamin D supplementation and milk intake on 25-hydroxyvitamin D level appeared similar regardless of skin pigmentation or season. CONCLUSION Two modifiable dietary intake variables (vitamin D supplementation and cow's milk intake) are the most important determinants of 25-hydroxyvitamin D status in early childhood.

  9. Differential conserted activity induced regulation of Nogo receptors (1-3, LOTUS and Nogo mRNA in mouse brain.

    Directory of Open Access Journals (Sweden)

    Tobias E Karlsson

    Full Text Available Nogo Receptor 1 (NgR1 mRNA is downregulated in hippocampal and cortical regions by increased neuronal activity such as a kainic acid challenge or by exposing rats to running wheels. Plastic changes in cerebral cortex in response to loss of specific sensory inputs caused by spinal cord injury are also associated with downregulation of NgR1 mRNA. Here we investigate the possible regulation by neuronal activity of the homologous receptors NgR2 and NgR3 as well as the endogenous NgR1 antagonist LOTUS and the ligand Nogo. The investigated genes respond to kainic acid by gene-specific, concerted alterations of transcript levels, suggesting a role in the regulation of synaptic plasticity, Downregulation of NgR1, coupled to upregulation of the NgR1 antagonist LOTUS, paired with upregulation of NgR2 and 3 in the dentate gyrus suggest a temporary decrease of Nogo/OMgp sensitivity while CSPG and MAG sensitivity could remain. It is suggested that these activity-synchronized temporary alterations may serve to allow structural alterations at the level of local synaptic circuitry in gray matter, while maintaining white matter pathways and that subsequent upregulation of Nogo-A and NgR1 transcript levels signals the end of such a temporarily opened window of plasticity.

  10. Children’s residential exposure to selected allergens and microbial indicators: endotoxins and (1→3-β-D-glucans

    Directory of Open Access Journals (Sweden)

    Anna Kozajda


    Full Text Available Objectives: The study was aimed at assessment of exposure to endotoxins, (1→3-β-D-glucans and mite, cockroach, cat, dog allergens present in settled dust in premises of children as agents which may be significantly correlated with the occurrence of allergic symptoms and diseases in children. Materials and Methods: The study covered 50 homes of one- or two-year-old children in Poland. Samples of settled dust were taken from the floor and the child's bed. The levels of (1→3-β-D-glucans (floor, endotoxins (floor and allergens of mite, cat, dog and cockroach (floor and bed were analyzed. Results: Average geometric concentrations (geometric standard deviation of endotoxins, (1→3-β-D-glucans, Der p1, Fel d1, Can f1 and Bla g1 in children homes were on the floor 42 166.0 EU/g (3.2, 20 478.4 ng/g (2.38, 93.9 ng/g (6.58, 119.8 ng/g (13.0, 288.9 ng/g (3.4, 0.72 U/g (4.4 and in their beds (only allergens 597.8 ng/g (14.2, 54.1 ng/g (4.4, 158.6 ng/g (3.1 0.6 U/g (2.9, respectively. When the floor was covered with the carpet, higher concentrations of endotoxins, (1→3-β-D-glucans and allergens (each type were found in the settled dust (p < 0.05. The trend was opposite in case of allergens (except dog analyzed from bed dust and significantly higher concentrations were found in the rooms with smooth floor (p < 0.05. Conclusions: Among the analyzed factors only the type of floor significantly modified both the level of biological indicators and allergens. The results of this study could be the base for verifying a hypothesis that carpeting may have a protective role against high levels of cockroach, dog and cat allergens.

  11. Sox2-Mediated Conversion of NG2 Glia into Induced Neurons in the Injured Adult Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Christophe Heinrich


    Full Text Available The adult cerebral cortex lacks the capacity to replace degenerated neurons following traumatic injury. Conversion of nonneuronal cells into induced neurons has been proposed as an innovative strategy toward brain repair. Here, we show that retrovirus-mediated expression of the transcription factors Sox2 and Ascl1, but strikingly also Sox2 alone, can induce the conversion of genetically fate-mapped NG2 glia into induced doublecortin (DCX+ neurons in the adult mouse cerebral cortex following stab wound injury in vivo. In contrast, lentiviral expression of Sox2 in the unlesioned cortex failed to convert oligodendroglial and astroglial cells into DCX+ cells. Neurons induced following injury mature morphologically and some acquire NeuN while losing DCX. Patch-clamp recording of slices containing Sox2- and/or Ascl1-transduced cells revealed that a substantial fraction of these cells receive synaptic inputs from neurons neighboring the injury site. Thus, NG2 glia represent a potential target for reprogramming strategies toward cortical repair.

  12. 1H NMR study of 2-deoxy-D-arabino-hexopyranose (2-deoxy-glucopyranose), 2-deoxy-D-lyxo-hexopyranose (2-deoxy-galactopyranose) and 2'-deoxy lactose

    International Nuclear Information System (INIS)

    Bruyn, A. de; Anteunis, M.


    Complete analyses of the 1 H n.m.r. spectra at 300 MHz of D 2 O solutions of 2-deoxy-D-arabino-hexopyranose, 2-deoxy-D-lyxo-hexopyranose and 2'-deoxy lactose. Chemical shifts in the deoxy monosaccharides and in 2'-deoxy lactose. Chemical shifts in the deoxy monosaccharides and in 2'-deoxy lactose are compared with those previously obtained in the parent aldeohexopyranoses, glucobioses and D-galactopyranosol-D-glucoses. Increment values are suggested in order to predict chemical shifts in 2-deoxy derivatives from the well known rules for aldohexopyranoses. (author)

  13. Expression of the dopaminergic D1 and D2 receptors in the anterior cingulate cortex in a model of neuropathic pain

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    Ortega-Legaspi J Manuel


    Full Text Available Abstract Background The anterior cingulate cortex (ACC has been related to the affective component of pain. Dopaminergic mesocortical circuits, including the ACC, are able to inhibit neuropathic nociception measured as autotomy behaviour. We determined the changes in dopamine D1 and D2 (D1R and D2R receptor expression in the ACC (cg1 and cg2 in an animal model of neuropathic pain. The neuropathic group had noxious heat applied in the right hind paw followed 30 min. later by right sciatic denervation. Autotomy score (AS was recorded for eight days and subsequently classified in low, medium and high AS groups. The control consisted of naïve animals. A semiquantitative RT-PCR procedure was done to determine mRNA levels for D1R and D2R in cg1 and cg2, and protein levels were measured by Western Blot. Results The results of D1R mRNA in cg1 showed a decrease in all groups. D2R mRNA levels in cg1 decreased in low AS and increased in medium and high AS. Regarding D1R in cg2, there was an increase in all groups. D2R expression levels in cg2 decreased in all groups. In cg1, the D2R mRNA correlated positively with autotomy behaviour. Protein levels of D2R in cg1 increased in all groups but to a higher degree in low AS. In cg2 D2R protein only decreased discretely. D1R protein was not found in either ACC region. Conclusions This is the first evidence of an increase of inhibitory dopaminergic receptor (D2R mRNA and protein in cg1 in correlation with nociceptive behaviour in a neuropathic model of pain in the rat.

  14. Aflatoxin M1 Contamination in Ice-Cream

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    R. Kazemi Darsanaki


    Full Text Available Aflatoxin M1 (AFM1 is the hydroxylated metabolite of aflatoxin B1 (AFB1 that it can be found in milk and dairy products. In this study, ELISA (Enzyme Linked Immunosorbent Assay technique was used for detection of AFM1 in ice-cream in Guilan province (Northern Iran. A total of 90 ice-cream samples was randomly obtained from different supermarkets. In 62 of the 90 ice-cream samples examined (68.88%, the presence of AFM1 was detected in concentrations between 8.4 -147.7 ng/l. The mean level of AFM1 in positive samples was 40.36 ng/l. AFM1 levels in 11 samples (12.22% were higher than the maximum tolerance limit (50 ng/l accepted by ISIRI, European Community and Codex Alimentarius.

  15. Blonanserin Ameliorates Phencyclidine-Induced Visual-Recognition Memory Deficits: the Complex Mechanism of Blonanserin Action Involving D3-5-HT2A and D1-NMDA Receptors in the mPFC (United States)

    Hida, Hirotake; Mouri, Akihiro; Mori, Kentaro; Matsumoto, Yurie; Seki, Takeshi; Taniguchi, Masayuki; Yamada, Kiyofumi; Iwamoto, Kunihiro; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro


    Blonanserin differs from currently used serotonin 5-HT2A/dopamine-D2 receptor antagonists in that it exhibits higher affinity for dopamine-D2/3 receptors than for serotonin 5-HT2A receptors. We investigated the involvement of dopamine-D3 receptors in the effects of blonanserin on cognitive impairment in an animal model of schizophrenia. We also sought to elucidate the molecular mechanism underlying this involvement. Blonanserin, as well as olanzapine, significantly ameliorated phencyclidine (PCP)-induced impairment of visual-recognition memory, as demonstrated by the novel-object recognition test (NORT) and increased extracellular dopamine levels in the medial prefrontal cortex (mPFC). With blonanserin, both of these effects were antagonized by DOI (a serotonin 5-HT2A receptor agonist) and 7-OH-DPAT (a dopamine-D3 receptor agonist), whereas the effects of olanzapine were antagonized by DOI but not by 7-OH-DPAT. The ameliorating effect was also antagonized by SCH23390 (a dopamine-D1 receptor antagonist) and H-89 (a protein kinase A (PKA) inhibitor). Blonanserin significantly remediated the decrease in phosphorylation levels of PKA at Thr197 and of NR1 (an essential subunit of N-methyl-D-aspartate (NMDA) receptors) at Ser897 by PKA in the mPFC after a NORT training session in the PCP-administered mice. There were no differences in the levels of NR1 phosphorylated at Ser896 by PKC in any group. These results suggest that the ameliorating effect of blonanserin on PCP-induced cognitive impairment is associated with indirect functional stimulation of the dopamine-D1-PKA-NMDA receptor pathway following augmentation of dopaminergic neurotransmission due to inhibition of both dopamine-D3 and serotonin 5-HT2A receptors in the mPFC. PMID:25120077

  16. Simultaneous quantitation of 2-acetyl-4-tetrahydroxybutylimidazole, 2- and 4-methylimidazoles, and 5-hydroxymethylfurfural in beverages by ultrahigh-performance liquid chromatography-tandem mass spectrometry. (United States)

    Wang, Jinyuan; Schnute, William C


    An ultrahigh-performance liquid chromatography (UHPLC) tandem mass spectrometric (MS/MS) method was developed for the simultaneous quantification of 2-acetyl-4-tetrahydroxybutylimidazole (THI), 2- and 4-methylimidazoles (2-MI and 4-MI), and 5-hydroxymethylfurfural (HMF) in beverage samples. A C30 reversed-phase column was used in this method, providing sufficient retention and total resolution for all targeted analytes, with an MS/MS instrument operated in selected reaction monitoring (SRM) mode for sensitive and selective detection using isotope-labeled 4-methyl-d(3)-imidazole (4-MI-d(3)) as the internal standard (IS). This method demonstrates lower limit of quantification (LLOQ) at 1 ng/mL and coefficient of determination (r(2)) >0.999 for each analyte with a calibration range established from 1 to 500 ng/mL. This method also demonstrates excellent quantification accuracy (84.6-105% at 5 ng/mL, n = 7), precision (RSD beverage samples were tested (n = 2) in this study including 13 dark-colored beverage samples with different flavors and varieties and 4 light-colored beverage samples. Three target analytes were quantified in these samples with concentrations in the range from 284 to 644 ng/mL for 4-MI and from 706 to 4940 ng/mL for HMF. THI was detected in only one sample at 6.35 ng/mL.

  17. Development of an impedimetric aptasensor for the determination of aflatoxin M1 in milk. (United States)

    Istamboulié, Georges; Paniel, Nathalie; Zara, Lorena; Reguillo Granados, Lucia; Barthelmebs, Lise; Noguer, Thierry


    An aptasensor was designed for the determination of aflatoxin M1 (AFM1) in milk based on DNA-aptamer recognition and electrochemical impedance spectroscopy detection. A hexaethyleneglycol-modified 21-mer oligonucleotide was immobilized on a carbon screen-printed electrode through carbodiimide immobilization, after diazonium activation of the sensing surface. Cyclic voltammetry and electrochemical impedance spectroscopy in the presence of ferri/ferrocyanide redox probe were used to characterize each step of the aptasensor development. Aptamer-AFM1 interaction induced an increase in electron-transfer resistance, allowing the determination of AFM1 in buffer in the range 2-150 ng/L (LOD=1.15 ng/L). Application to milk analysis showed that a preliminary treatment was mandatory. A simple filtration through a 0.2 µm PTFE membrane allowed determination of AFM1 in milk for concentrations ranging from 20 to 1000 ng/kg. These performances are compatible with the AFM1 levels set in European Union for milk and dairy products for adults (50 ng/kg) and infants (25 ng/kg). Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Characterization of polarized THP-1 macrophages and polarizing ability of LPS and food compounds. (United States)

    Chanput, Wasaporn; Mes, Jurriaan J; Savelkoul, Huub F J; Wichers, Harry J


    Little is known about the polarizing potential of currently used human macrophage cell lines, while a better understanding phenomena can support the prediction of effects in vivo based on in vitro analysis. To test the polarization capability of PMA differentiated-THP-1 macrophages (M0), cells were stimulated with 20 ng ml(-1) IFNγ + 1 μg ml(-1) LPS and 20 ng ml(-1) IL-4, which are known to influence macrophage polarization in vivo and ex vivo into the M1 and M2 state, respectively. Apart from several well-known M1 and M2 markers, also new possible markers for M1 and M2 polarization were analysed in this study. The expression of M1 marker genes was up-regulated in IFNγ + LPS stimulated-M0 THP-1 macrophages. The IL-4 stimulated-M0 THP-1 macrophages expressed M2 cell membrane receptor genes. However, M2 chemokine and their receptor genes were only slightly up-regulated which might be due to the complexity of the secondary cell-cell interaction of the chemokine system. Lipopolysaccharides from E. coli (LPS) and food compounds [lentinan, vitamin D3 (vD3) and the combination of lentinan + vitamin D3 (Len + vD3)] were investigated for their polarizing ability on M0 THP-1 macrophages towards either the M1 or M2 state. LPS (700 ng ml(-1)) was able to skew M0 THP-1 macrophages towards the M1 direction since all analysed M1 marker genes were strongly expressed. Lentinan, vD3 and Len + vD3 did not induce expression of either M1 or M2 markers, indicating no polarizing ability of these compounds. Based on the expression of M1 and M2 marker genes we concluded that THP-1 macrophages could be successfully polarized into either the M1 or M2 state. Therefore, they can be used as a new macrophage polarizing model to estimate the polarizing/switching ability of test food compounds.

  19. Expression of Flk-1 and Cyclin D2 mRNA in the Myocardium of Rats with Doxorubicin-Induced Cardiomyopathy and after Treatment with Betulonic Acid Amide. (United States)

    Mzhelskaya, M M; Klinnikova, M G; Koldysheva, E V; Lushnikova, E L


    The expression of VEGFR2 (Flk-1, according to immunohistochemistry) and of cyclin D2 mRNA (according to real-time PCR) in the myocardium of rats is studied in doxorubicin-induced cardiomyopathy and in response to betulonic acid amide. Doxorubicin alone and in combination with betulonic acid amide causes after 3 days a manifest reduction of cyclin D2 mRNA expression (by 38 and 63%, respectively), while injection of betulonic acid amide alone causes a 23-fold increase of cyclin D2 mRNA expression. An increase of cyclin D2 mRNA expression has been detected in all experimental groups after 14 days of experiment, the most pronounced in response to betulonic acid amide (63 times). The expression of Flk-1 in cardiomyocytes increases significantly in response to both chemical agents starting from day 3 of experiment. These results indicate that doxorubicin and betulonic acid amide induce cytoprotective reactions in the myocardium, first at the intracellular, then at the cellular levels.

  20. Bradykinin-activated transmembrane signals are coupled via N/sub o/ or N/sub i/ to production of inositol 1,4,5-trisphosphate, a second messenger in NG108-15 neuroblastoma-glioma hybrid cells

    International Nuclear Information System (INIS)

    Higashida, H.; Streaty, R.A.; Klee, W.; Nirenberg, M.


    The addition of bradykinin to NG108-15 cells results in a transient hyperpolarization followed by prolonged cell depolarization. Injection of inositol 1,4,5-trisphosphate or Ca 2+ into the cytoplasm of NG108-15 cells also elicits cell hyperpolarization followed by depolarization. Tetraethylammonium ions inhibit the hyperpolarizing response of cells to bradykinin or inositol 1,4,5-trisphosphate. Thus, the hyperpolarizing phase of the cell response may be due to inositol 1,4,5-trisphosphate-dependent release of stored 45 Ca-labelled Ca 2+ into the cytoplasm, which activates Ca 2+ -dependent K + channels. The depolarizing phase of the cell response to bradykinin is due largely to inhibition of M channels, thereby decreasing the rate of K + efflux from cells and, to a lesser extent, to activation of Ca 2+ -dependent ion channels and Ca 2+ channels. In contrast, injection of inositol 1,4,5-trisphosphate or Ca 2+ into the cytosol did not alter M channel activity. Incubation of NG108-15 cells with pertussis toxin inhibits bradykinin-dependent cell hyperpolarization and depolarization. Bradykinin stimulates low K/sub m/ GTPase activity and inhibits adenylate cyclase in NG108-15 membrane preparations but not in membranes prepared from cells treated with pertussis toxin. These results show that [bradykinin-receptor] complexes interact with N/sub o/ or N/sub i/ and suggest that N/sub o/ and/or N/sub i/ mediate the transduction of signals from bradykinin receptors to phospholipase C and adenylate cyclase

  1. Properties of M1-M2-Si-Al-O-N glasses (M1 = La or Nd, M2 = Y or Er)

    Energy Technology Data Exchange (ETDEWEB)

    Pomeroy, M.J.; Nestor, E.; Hampshire, S. [Limerick Univ. (Ireland). Materials and Surface Science Inst.; Ramesh, R. [Littelfuse Ireland, Dundalk, Co. Louth (Ireland)


    Mixed lanthanide cation oxynitride glasses have been prepared in the M1 - M2 - Si-Al-O-N systems where M1 = La or Nd and M2 = Y or Er. The densities ({rho}), Young's moduli (E), microhardnesses (H{sub v}), glass transition temperatures (T{sub g}), dilatometric softening temperatures (T{sub dil}) and coefficients of thermal expansion (CTE) of 13 glasses were determined. The molar volume values (MV) calculated from density data, E, H{sub v}, T{sub g}, T{sub dil} and CTE values were all found to vary linearly with the effective cation field strength arising from the M1 and M2 modifier cations. Least squares intercept and slope values are presented which correlate each property to effective cation field strength together with error values which arise from glass and specimen preparation and measurement inconsistencies. These linear correlations clearly indicate that the overall glass structure remains the same for each of the thirteen glasses with only the modifier cation(s) having any influence. This influence appears to be a cross-linking effect, the strength of which increases as the effective cation field strength of the M1, M2 modifiers increases. (orig.)

  2. Possible impact of the CYP2D6*10 polymorphism on the nonlinear pharmacokinetic parameter estimates of paroxetine in Japanese patients with major depressive disorders

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    Saruwatari J


    Full Text Available Junji Saruwatari,1 Hiroo Nakashima,1 Shoko Tsuchimine,2 Miki Nishimura,1 Naoki Ogusu,1 Norio Yasui-Furukori21Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan; 2Department of Neuropsychiatry, Graduate School of Medicine, Hirosaki University, Hirosaki, JapanAbstract: It has been suggested that the reduced function allele with reduced cytochrome P450 (CYP 2D6 activity, CYP2D6*10, is associated with the interindividual differences in the plasma paroxetine concentrations, but there is no data presently available regarding the influence of the CYP2D6*10 polymorphism on the pharmacokinetic parameters, eg, Michaelis–Menten constant (Km and maximum velocity (Vmax, in Asian populations. The present study investigated the effects of the CYP2D6 polymorphisms, including CYP2D6*10, on the pharmacokinetic parameters of paroxetine in Japanese patients with major depressive disorders. This retrospective study included 15 Japanese patients with major depressive disorders (four males and eleven females who were treated with paroxetine. The CYP2D6*2, CYP2D6*4, CYP2D6*5, CYP2D6*10, CYP2D6*18, CYP2D6*39, and CYP2D6*41 polymorphisms were evaluated. A total of 56 blood samples were collected from the patients. The Km and Vmax values of paroxetine were estimated for each patient. The allele frequencies of CYP2D6*2, CYP2D6*4, CYP2D6*5, CYP2D6*10, CYP2D6*18, CYP2D6*39, and CYP2D6*41 were 6.7%, 0%, 10.0%, 56.7%, 0%, 26.7%, and 0%, respectively. The mean values of Km and Vmax were 50.5±68.4 ng/mL and 50.6±18.8 mg/day, respectively. Both the Km and Vmax values were significantly smaller in CYP2D6*10 allele carriers than in the noncarriers (24.2±18.3 ng/mL versus 122.5±106.3 ng/mL, P=0.008; 44.2±16.1 mg/day versus 68.3±15.0 mg/day, P=0.022, respectively. This is the first study to demonstrate that the CYP2D6*10 polymorphism could affect the nonlinear pharmacokinetic parameter estimates of

  3. Couplings in D(2,1;α) superconformal mechanics from the SU(2) perspective

    Energy Technology Data Exchange (ETDEWEB)

    Galajinsky, Anton [Laboratory of Mathematical Physics, Tomsk Polytechnic University,Lenin Ave. 30, 634050 Tomsk (Russian Federation)


    Dynamical realizations of the most general N=4 superconformal group in one dimension D(2,1;α) are reconsidered from the perspective of the R-symmetry subgroup SU(2). It is shown that any realization of the R-symmetry subalgebra in some phase space can be extended to a representation of the Lie superalgebra corresponding to D(2,1;α). Novel couplings of arbitrary number of supermultiplets of the type (1,4,3) and (0,4,4) to a single supermultiplet of either the type (3,4,1), or (4,4,0) are constructed. D(2,1;α) superconformal mechanics describing superparticles propagating near the horizon of the extreme Reissner-Nordström-AdS-dS black hole in four and five dimensions is considered. The parameter α is linked to the cosmological constant.

  4. Determination of eight nitrosamines in water at the ng L{sup -1} levels by liquid chromatography coupled to atmospheric pressure chemical ionization tandem mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Ripolles, Cristina; Pitarch, Elena; Sancho, Juan V; Lopez, Francisco J [Research Institute for Pesticides and Water, University Jaume I, Avda. Sos Baynat, E-12071 Castellon (Spain); Hernandez, Felix [Research Institute for Pesticides and Water, University Jaume I, Avda. Sos Baynat, E-12071 Castellon (Spain)


    Highlights: {center_dot} Eight N-nitrosamines in water by LC(APCI)MS/MS QqQ analysis. {center_dot} Validation at two levels: 10 ng L{sup -1} (LOQ) and 100 ng L{sup -1} in drinking water. {center_dot} Developed method applied to different types of water samples. {center_dot} NDMA was the analyte more frequently detected and at the highest concentration levels. - Abstract: In this work, we have developed a sensitive method for detection and quantification of eight N-nitrosamines, N-nitrosodimethylamine (NDMA), N-nitrosomorpholine (NMor), N-nitrosomethylethylamine (NMEA), N-nitrosopirrolidine (NPyr), N-nitrosodiethylamine (NDEA), N-nitrosopiperidine (NPip), N-nitroso-n-dipropylamine (NDPA) and N-nitrosodi-n-butylamine (NDBA) in drinking water. The method is based on liquid chromatography coupled to tandem mass spectrometry, using atmospheric pressure chemical ionization (APCI) in positive mode with a triple quadrupole analyzer (QqQ). The simultaneous acquisition of two MS/MS transitions in selected reaction monitoring mode (SRM) for each compound, together with the evaluation of their relative intensity, allowed the simultaneous quantification and reliable identification in water at ppt levels. Empirical formula of the product ions selected was confirmed by UHPLC-(Q)TOF MS accurate mass measurements from reference standards. Prior to LC-MS/MS QqQ analysis, a preconcentration step by off-line SPE using coconut charcoal EPA 521 cartridges (by passing 500 mL of water sample) was necessary to improve the sensitivity and to meet regulation requirements. For accurate quantification, two isotope labelled nitrosamines (NDMA-d{sub 6} and NDPA-d{sub 14}) were added as surrogate internal standards to the samples. The optimized method was validated at two concentration levels (10 and 100 ng L{sup -1}) in drinking water samples, obtaining satisfactory recoveries (between 90 and 120%) and precision (RSD < 20%). Limits of detection were found to be in the range of 1-8 ng L{sup -1

  5. DFT study on oxidation of HS(CH2) m SH ( m = 1-8) in oxidative desulfurization (United States)

    Song, Y. Z.; Song, J. J.; Zhao, T. T.; Chen, C. Y.; He, M.; Du, J.


    Density functional theory was employed for calculation of HS(CH2) m SH ( m = 1-8) and its derivatives at B3LYP method at 6-31++g ( d, p) level. Using eigenvalues of LUMO and HOMO for HS(CH2) m SH, the standard electrode potentials were estimated by a stepwise multiple regression techniques (MLR), and obtained as E° = 1.500 + 7.167 × 10-3 HOMO-0.229 LUMO with high correlation coefficients of 0.973 and F values of 43.973.

  6. Ab-initio study of the stability of the D8{sub m}-Nb{sub 5}Sn{sub 2}Ga and D8{sub m}-Ta{sub 5}SnGa{sub 2} compounds

    Energy Technology Data Exchange (ETDEWEB)

    Colinet, Catherine, E-mail: [Science et Ingénierie des Matériaux et Procédés, Grenoble INP, UJF, CNRS, 38402 Saint Martin d’Hères Cedex (France); Tedenac, Jean-Claude [Institut de Chimie Moléculaire et des Matériaux I.C.G., UMR-CNRS 5253, Université Montpellier II, Place E. Bataillon, 34095 Montpellier Cedex 5 (France)


    Graphical abstract: Thermodynamic data along the sections Ta{sub 5}Sn{sub 3}–Ta{sub 5}Ga{sub 3} at low and high temperature. - Highlights: • First principles calculations were performed along sections V{sub 5}Sn{sub 3}–V{sub 5}Ga{sub 3}, Nb{sub 5}Sn{sub 3}–Nb{sub 5}Ga{sub 3}, and Ta{sub 5}Sn{sub 3}–Ta{sub 5}Ga{sub 3}. • The ternary compound D8{sub m}-Nb{sub 5}Sn{sub 2}Ga is stable. • The phase D8{sub m}-Ta{sub 5}SnGa{sub 2} is stable in the D8{sub m} structure. • In this phase, the Sn and Ga atoms share the 8h sites. - Abstract: First principles calculations have been performed in the T–Sn–Ga (T = V, Nb, Ta) systems along the section x{sub T} = 0.625. The enthalpies of formation of the binary and ternary D8{sub m}, D8{sub 1}, and D8{sub 8} structures have been calculated. In the V–Sn–Ga system, no ternary structure is stable in the section. In the Nb–Sn–Ga system, the ternary compound D8{sub m}-Nb{sub 5}Sn{sub 2}Ga is stable. In the Ta–Sn–Ga system, a combination of the ab-initio calculations and Gibbs energy calculations using the sublattice model allows the show that the phase D8{sub m}-Ta{sub 5}(Sn,Ga){sub 2}Ga with a mixed occupancy of the 8h sites of the structure by Ga and Sn atoms is stable at high temperature due to the configurational entropy. These results are in agreement with the experimental determinations previously published in the literature.

  7. Suberoylanilide hydroxamic acid (SAHA) inhibits EGF-induced cell transformation via reduction of cyclin D1 mRNA stability

    International Nuclear Information System (INIS)

    Zhang, Jingjie; Ouyang, Weiming; Li, Jingxia; Zhang, Dongyun; Yu, Yonghui; Wang, York; Li, Xuejun; Huang, Chuanshu


    Suberoylanilide hydroxamic acid (SAHA) inhibiting cancer cell growth has been associated with its downregulation of cyclin D1 protein expression at transcription level or translation level. Here, we have demonstrated that SAHA inhibited EGF-induced Cl41 cell transformation via the decrease of cyclin D1 mRNA stability and induction of G0/G1 growth arrest. We found that SAHA treatment resulted in the dramatic inhibition of EGF-induced cell transformation, cyclin D1 protein expression and induction of G0/G1 growth arrest. Further studies showed that SAHA downregulation of cyclin D1 was only observed with endogenous cyclin D1, but not with reconstitutionally expressed cyclin D1 in the same cells, excluding the possibility of SAHA regulating cyclin D1 at level of protein degradation. Moreover, SAHA inhibited EGF-induced cyclin d1 mRNA level, whereas it did not show any inhibitory effect on cyclin D1 promoter-driven luciferase reporter activity under the same experimental conditions, suggesting that SAHA may decrease cyclin D1 mRNA stability. This notion was supported by the results that treatment of cells with SAHA decreased the half-life of cyclin D1 mRNA from 6.95 h to 2.57 h. Consistent with downregulation of cyclin D1 mRNA stability, SAHA treatment also attenuated HuR expression, which has been well-characterized as a positive regulator of cyclin D1 mRNA stability. Thus, our study identifies a novel mechanism responsible for SAHA inhibiting cell transformation via decreasing cyclin D1 mRNA stability and induction of G0/G1 growth arrest in Cl41 cells. -- Highlights: ► SAHA inhibits cell transformation in Cl41 cells. ► SAHA suppresses Cyclin D1 protein expression. ► SAHA decreases cyclin D1 mRNA stability.

  8. Preliminary Antenna Concept for the ngVLA (United States)

    Di Francesco, James; Selina, Robert; Grammer, Wes; McKinnon, Mark M.


    The preliminary concept for a Next Generation Very Large Array (ngVLA) calls for an interferometric array having an effective collecting area and spatial resolution that are both 10 times better than that of the current VLA and operating over a frequency range of 1.2-116 GHz. Given the large number of antennas needed to meet the collecting area goal, the ngVLA antenna concept must strike a balance between competing science requirements and the programmatic targets for the array’s life cycle cost.Antenna diameters currently under consideration for the ngVLA are in the range of 12-25 m, with a nominal 18-m diameter aperture used for the conceptual design. Currently, the optimization for operations and construction cost suggests that a smaller number of larger apertures is preferable.The surface accuracy goal for the antennas is 185 µm rms (λ/16 @ 100 GHz) for the primary and subreflector combined under optimal environmental conditions. The subreflector will be optimized for performance above 10 GHz, with some degradation in aperture efficiency accepted at lower frequencies.For high dynamic range imaging, particularly at the low end of the ngVLA’s frequency range, the optimum optical configuration is likely an offset geometry. An unblocked aperture will minimize scattering, spillover, and sidelobe pickup. Both performance and maintenance requirements favor a receiver feedarm on the low side of the reflector.High pointing accuracy will also be necessary to provide the imaging dynamic range required of the system. With an unblocked aperture, variations in the antenna gain pattern are expected to be dominated by pointing errors. Preliminary requirements are for an absolute pointing accuracy of 40” RMS, with referenced pointing of 3” RMS (FWHM/10 at 10 GHz and 120 GHz, respectively, for an 18-m diameter dish).The antenna mount is expected to be a typical altitude-azimuth design. Both pedestal bearing and rail-based azimuth drives are under consideration. If fast

  9. [Prevalence of hypovitaminosis D and associated factors in Spanish population of school children and adolescents]. (United States)

    Durá-Travé, Teodoro; Gallinas-Victoriano, Fidel; Chueca-Guindulain, María Jesús; Berrade-Zubiri, Sara; Moreno-Gónzalez, Paula; Malumbres-Chacón, María


    To analyse the prevalence of hypovitaminosisD and associated factors in school children and adolescents living in a region of northern Spain. Cross-sectional study (convenience sampling). Primary Health Care. A total of 602 Caucasian individuals (aged 3.1 to 15.4years) were included in the study. Prevalence of hypovitaminosisD were calculated (dependent variable). HypovitaminosisD is defined according to the US Endocrine Society criteria: deficiency (calcidiol <20ng/mL), insufficiency (calcidiol: 20-29ng/mL), and sufficiency (calcidiol ≥30ng/mL). Gender, age, body mass index, residence, and season of the year were recorded (independent variables), and their association with hypovitaminosisD was analysed by multiple regression. The prevalence of hypovitaminosisD was 60.4% (insufficiency: 44.6%; deficiency: 15.8%). Multivariate analysis showed that factors associated to hypovitaminosisD were being female (OR: 1.6; 95%CI: 1.1-2.3), pubertal age (OR: 1.8; 95%CI: 1.2-2.6), autumn (OR: 9.5; 95%CI: 4.8-18.7), winter (OR: 8.8; 95%CI: 4.5-17.5) and spring time (OR: 13.2; 95%CI: 6.4-27.5), living in urban areas (OR:1.6; CI95%: 1.1-2.2), and severe obesity (OR: 4.4; 95%CI: 1.9-10.3). There is a high prevalence of hypovitaminosisD in juvenile populations. being female, pubertal age, autumn, winter and spring seasons, severe obesity, and living in urban areas are factors associated to hypovitaminosisD. Consideration should be given to the administration of vitamin supplements and/or the increase in the ingestion of natural vitaminD dietary sources. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  10. mTOR-inhibitor treatment of metastatic renal cell carcinoma: contribution of Choi and modified Choi criteria assessed in 2D or 3D to evaluate tumor response

    Energy Technology Data Exchange (ETDEWEB)

    Lamuraglia, M. [Laboratoire d' Imagerie Biomedicale, Sorbonne Universites, UPMC Univ Paris 06, INSERM, CNRS, Paris (France); Raslan, S.; Penna, R.R.; Wagner, M. [Groupe Hospitalier Pitie-Salpetriere, APHP UPMC, Service de Radiologie Polyvalente et Oncologique, Paris Cedex 13 (France); Elaidi, R.; Oudard, S. [APHP, Oncology Unit, Georges-Pompidou Hospital, Paris (France); Escudier, B. [Gustave-Roussy Institute, Medical Oncology Department, Villejuif (France); Slimane, K. [Novartis Pharma, Rueil-Malmaison (France); Lucidarme, O. [Groupe Hospitalier Pitie-Salpetriere, APHP UPMC, Service de Radiologie Polyvalente et Oncologique, Paris Cedex 13 (France); Laboratoire d' Imagerie Biomedicale, Sorbonne Universites, UPMC Univ Paris 06, INSERM, CNRS, Paris (France)


    To determine whether 2D or 3D Choi and modified Choi (mChoi) criteria could assess the efficacy of everolimus against metastatic renal cell carcinoma (mRCC). RECIST-1.1, Choi, and mChoi criteria were applied retrospectively to analyse baseline and 2-month contrast-enhanced computed tomography (CECT) images in 48 patients with mRCC enrolled in the everolimus arm of the French randomized double-blind multicentre phase III trial comparing everolimus versus placebo (RECORD-1). The primary endpoint was centrally reviewed progression-free survival (PFS) calculated from the initial RECORD-1 analysis. Mean attenuation was determined for 2D target lesion regions of interest drawn on CECT sections whose largest diameters had been measured, and for the 3D whole target lesion. The median PFS was 5.5 months. The median PFS for everolimus responders defined using 3D mChoi criteria was significantly longer than for non-responders (7.6 versus 5.4 months, respectively), corresponding to a hazard ratio for progression of 0.45 (95 % CI: 0.22-0.92), with respective 1-year survival rates of 31 % and 9 %. No other 2D or 3D imaging criteria at 2 months identified patients who would benefit from everolimus. At 2 months, only 3D mChoi criteria were able to identify mRCC patients with a PFS benefit from everolimus. (orig.)

  11. The Role of NG2 Glial Cells in ALS Pathogenesis (United States)


    attached and cells migrated out from the spheres. Some had typical OPC morphology (figure 2A), bipolar and tripolar . More importantly, they...cells showed NG2 and Olig2 expression (Figure 5B) after being cultured. After being treated with T3, some cells changed their bipolar and tripolar

  12. Vitamin D Status and Related Factors in Newborns in Shanghai, China

    Directory of Open Access Journals (Sweden)

    Xiaodan Yu


    Full Text Available With the increasing recognition of the importance of the non-skeletal effects of vitamin D (VitD, more and more attention has been drawn to VitD status in early life. However, the VitD status of newborns and factors that influence VitD levels in Shanghai, China, remain unclear. A total of 1030 pregnant women were selected from two hospitals in Shanghai, one of the largest cities in China located at 31 degrees north latitude. Umbilical cord serum concentrations of 25-hydroxy vitamin D [25(OHD] were measured by LC-MS-MS, and questionnaires were used to collect information. The median cord serum 25(OHD concentration was 22.4 ng/mL; the concentration lower than 20 ng/mL accounted for 36.3% of the participants, and the concentration lower than 30 ng/mL for 84.1%. A multivariable logistic regression model showed that the determinants of low 25(OHD status were being born during autumn or winter months and a lack of VitD-related multivitamin supplementation. The relative risk was 1.7 for both autumn (95% CI, 1.12.6 and winter (95% CI, 1.12.5 births (p < 0.05. VitD-related multivitamin supplementation more than once a day during pregnancy reduced the risk of VitD deficiency [adjusted OR (aOR = 0.6, 95% CI (0.45–1.0 for VitD supplementation] (p < 0.05. VitD deficiency and insufficiency are common in newborns in Shanghai, China, and are independently associated with season and VitD supplementation. Our findings may assist future efforts to correct low levels of 25(OHD in Shanghai mothers and their newborn children.

  13. Radioimmunoassay of serum d-Norgestrel in women following oral and intravaginal administration

    International Nuclear Information System (INIS)

    Stanczyk, F.Z.; Hiroi, M.; Goebelsmann, U.; Brenner, P.F.; Lumkin, M.E.; Mishell, D.R. Jr.


    A radioimmunoassay (RIA) method for measuring d-Norgestrel (d-Ng) in serum has been developed utilizing petroleum ether extraction, an antiserum raised against d-Norgestrel-3-(0-carboxymethyl) oxime-epsilon-aminocaproic acid--boxine serum albumin, d-Norgestrel-3-(0-carboxymethyl) imino-[ 125 I]-iodohistamine, and dextran-coated charcoal separation. Control serum blanks were undetectable, 6 pg of d-Ng was measurable in 0.1 ml of serum with a high reliability, and intra- and interassay coefficients of variation were 4.4 and 4.9 percent, respectively. d-Ng added to control serum was quantitatively recovered. This RIA proved to be highly specific for d-Ng, cross-reacting less than 0.01 percent with 1-Ng and some 4 to 8 percent with 5α- and 5β-tetrahydro-d-Ng. Serum d-Ng levels measured in 3 women after ingestion of 75 μg of dl-Ng rose to 1.5 to 2 ng/ml within 1/2 to 2-3 hours after oral intake and fell rapidly thereafter to 0.2 to 0.4 ng/ml within 24 hours. Insertion of Silastic intravaginal rings (IVRs), containing 50 or 100 mg of dl-Ng, into 3 women for periods of 3 weeks resulted in a rapid rise of serum d-Ng after insertion. Serum d-Ng levels were highest 24 to 48 hours after the first insertion of each IVR, reaching peak levels of about 5 and 7 to 11 ng/ml, respectively, and declined gradually during the ensuing 15 to 20 days to some 30 to 40 percent of the peak serum d-Ng concentration. Serum d-Ng levels attained after IVR reinsertion remained relatively constant at 1 to 3 ng/ml during each subsequent cycle in all subjects and fell rapidly after each IVR removal. Serum estradiol and progesterone concentrations, measured about 3 times a week in these patients, indicated that ovulation was consistently inhibited

  14. Elevation of plasma milrinone concentrations in stage D heart failure associated with renal dysfunction. (United States)

    Cox, Zachary L; Calcutt, Marion W; Morrison, Thomas B; Akers, Wendell S; Davis, Mary Beth; Lenihan, Daniel J


    To determine steady state milrinone concentrations in patients with stage D heart failure (HF) with and without renal dysfunction We retrospectively identified patients with stage D HF at a single medical center on continuous milrinonein fusion at the time of plasma collection for entry into a research registry database. Milrinone was prescribed and titrated to improve hemodynamic and clinical status by a cardiologist. Plasma samples were obtained at steady state milrinone concentrations. Patients were stratified by creatinine clearance (CrCl) into 4 groups: group 1 (CrCl >60 mL/min), group 2 (CrCl 60-30 mL/min), group 3 (CrCl milrinone hemodynamic changes by cardiac catheterization and electrophysiologic changes by implantable cardiac defibrillator (ICD) interrogation. A total of 29 patients were identified: group 1 (n=14), group 2 (n=10), group 3(n=3), and group 4 (n = 2). The mean infusion rate (0.391+0.08 mg/kg/min) did not differ between groups (P=0.14). The mean milrinone concentration was 451+243 ng/mL in group 1, 591+293 ng/mL in group 2, 1575+962 ng/mL in group 3, and 6252+4409 ng/mL in group 4 (Pmilrinone hemodynamic improvements between the groups (P=0.41). The ICD interrogation revealed limited comparisons, but 6 of the 8 post milrinone ventricular tachycardia episodes requiring defibrillation occurred in group 4 patients. Patients with stage D HF having severe renal dysfunction have elevated milrinone concentrations. Future studies of milrinone concentrations are warranted to investigate the potential risk of life-threatening arrhythmias and potential dosing regimens in renal dysfunction.

  15. Comparison of Bit Error Rate of Line Codes in NG-PON2

    Directory of Open Access Journals (Sweden)

    Tomas Horvath


    Full Text Available This article focuses on simulation and comparison of line codes NRZ (Non Return to Zero, RZ (Return to Zero and Miller’s code for NG-PON2 (Next-Generation Passive Optical Network Stage 2 using. Our article provides solutions with Q-factor, BER (Bit Error Rate, and bandwidth comparison. Line codes are the most important part of communication over the optical fibre. The main role of these codes is digital signal representation. NG-PON2 networks use optical fibres for communication that is the reason why OptSim v5.2 is used for simulation.

  16. Cyclin D1 expression in prostate carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, R.A.; Ravinal, R.C.; Costa, R.S.; Lima, M.S. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Tucci, S. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Cirurgia e Anatomia, Divisão de Urologia, Ribeirão Preto, SP, Brasil, Divisão de Urologia, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Muglia, V.F. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Medicina Interna (Centro de Ciência da Imagem), Ribeirão Preto, SP, Brasil, Departamento de Medicina Interna (Centro de Ciência da Imagem), Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Reis, R.B. Dos [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Cirurgia e Anatomia, Divisão de Urologia, Ribeirão Preto, SP, Brasil, Divisão de Urologia, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Silva, G.E.B. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)


    The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness.

  17. Cyclin D1 expression in prostate carcinoma

    International Nuclear Information System (INIS)

    Pereira, R.A.; Ravinal, R.C.; Costa, R.S.; Lima, M.S.; Tucci, S.; Muglia, V.F.; Reis, R.B. Dos; Silva, G.E.B.


    The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness

  18. Determination of piperphentonamine and metabolites M1 and M6 in human plasma and urine by LC/MS/MS and its application in a pharmacokinetics study in Chinese healthy volunteers. (United States)

    Shi, Aixin; Hu, Xin; Li, Kexin; Li, Jian; Han, Liping; Wan, Huayin; Li, Rubing


    Piperphentonamine hydrochloride (PPTA) is a new calcium sensitizer. A liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for determination of piperphentonamine and its metabolites M1 and M6 was developed for the first time and applied to a pharmacokinetics study. Protein precipitation was used for pre-treatment of plasma samples, and solid phase extraction method was used for pre-treatment of urine samples. The chromatographic separation was achieved on a C(18) column using gradient elution in this study: A: 1% acetic acid aqueous solution, and B: acetonitrile. The whole analysis lasted for 10.5min and the gradient flow rate was 0.25mL/min constantly. The detection was performed of a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via a positive electrospray ionization source. The results were that the m/z ratios of monitored precursor ions and product ions of PPTA, M1 and M6 were 354.0→191.8, 356.0→148.7 and 358.0→148.7, respectively. From the standard curve, the concentration ranges of both PPTA and M1 in blood and urine samples were 0.1-500ng/mL and 0.1-200ng/mL, respectively; the concentration ranges of M6 in blood sample and urine sample were 0.2-500ng/mL and 0.2-200ng/mL, respectively; and the correlation coefficient of standard curve was r>0.99. A total of 31 healthy Chinese subjects participated in the pharmacokinetic study of single bolus intravenous injection of piperphentonamine hydrochloride. They were divided into three dosage groups and given 0.2, 0.4 and 0.6mg/kg of PPTA. After drug administration, concentrations of PPTA, M1 and M6 in human plasma and urine samples were determined to evaluation the pharmacokinetic characteristics of PPTA and its metabolites M1 and M6. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Audio zesilovač 2.1 ve třídě D pro laboratorní výuku


    Kolečková, Klára


    Práce se zabývá návrhem zapojení a konstrukcí audio zesilovače ve třídě D s pulsně šířkovou modulací. Výsledné zapojení je tvořeno ochranou napájení, aktivní výhybkou a samotným koncovým zesilovacím stupněm. Zesilovač je vytvořen v konfiguraci 2.1, středovýškový zesilovač má výstupní výkon 2 × 30 W na zátěži 8 , subwoofer 1 × 100 W na zátěži 2 . Řídicím centrem celého zapojení je integrovaný obvod TPA3116D2 od firmy Texas Instruments. Výsledný audio zesilovač bude využit jako přípravek pro la...

  20. Truncated thioredoxin (Trx-80) promotes pro-inflammatory macrophages of the M1 phenotype and enhances atherosclerosis. (United States)

    Mahmood, Dler Faieeq Darweesh; Abderrazak, Amna; Couchie, Dominique; Lunov, Oleg; Diderot, Vimala; Syrovets, Tatiana; Slimane, Mohamed-Naceur; Gosselet, Fabien; Simmet, Thomas; Rouis, Mustapha; El Hadri, Khadija


    Vascular cells are particularly susceptible to oxidative stress that is believed to play a key role in the pathogenesis of cardiovascular disorders. Thioredoxin-1 (Trx-1) is an oxidative stress-limiting protein with anti-inflammatory and anti-apoptotic properties. In contrast, its truncated form (Trx-80) exerts pro-inflammatory effects. Here we analyzed whether Trx-80 might exert atherogenic effects by promoting macrophage differentiation into the M1 pro-inflammatory phenotype. Trx-80 at 1 µg/ml significantly attenuated the polarization of anti-inflammatory M2 macrophages induced by exposure to either IL-4 at 15 ng/ml or IL-4/IL-13 (10 ng/ml each) in vitro, as evidenced by the expression of the characteristic markers, CD206 and IL-10. By contrast, in LPS-challenged macrophages, Trx-80 significantly potentiated the differentiation into inflammatory M1 macrophages as indicated by the expression of the M1 cytokines, TNF-α and MCP-1. When Trx-80 was administered to hyperlipoproteinemic ApoE2.Ki mice at 30 µg/g body weight (b.w.) challenged either with LPS at 30 µg/30 g (b.w.) or IL-4 at 500 ng/30 g (b.w.), it significantly induced the M1 phenotype but inhibited differentiation of M2 macrophages in thymus and liver. When ApoE2.Ki mice were challenged once weekly with LPS for 5 weeks, they showed severe atherosclerotic lesions enriched with macrophages expressing predominantly M1 over M2 markers. Such effect was potentiated when mice received daily, in addition to LPS, the Trx-80. Moreover, the Trx-80 treatment led to a significantly increased aortic lesion area. The ability of Trx-80 to promote differentiation of macrophages into the classical proinflammatory phenotype may explain its atherogenic effects in cardiovascular diseases. Copyright © 2013 Wiley Periodicals, Inc.

  1. Pro-Resolving Effects of Resolvin D2 in LTD4 and TNF-α Pre-Treated Human Bronchi.

    Directory of Open Access Journals (Sweden)

    Rayan Khaddaj-Mallat

    Full Text Available Inflammation is a major burden in respiratory diseases, resulting in airway hyperresponsiveness. Our hypothesis is that resolution of inflammation may represent a long-term solution in preventing human bronchial dysfunctions. The aim of the present study was to assess the anti-inflammatory effects of RvD2, a member of the D-series resolving family, with concomitant effects on ASM mechanical reactivity. The role and mode of action of RvD2 were assessed in an in vitro model of human bronchi under pro-inflammatory conditions, induced either by 1 μM LTD4 or 10 ng/ml TNF-α pre-treatment for 48h. TNF-α and LTD4 both induced hyperreactivity in response to pharmacological stimuli. Enhanced 5-Lipoxygenase (5-LOX and cysteinyl leukotriene receptor 1 (CysLTR1 detection was documented in LTD4 or TNF-α pre-treated human bronchi when compared to control (untreated human bronchi. In contrast, RvD2 treatments reversed 5-LOX/β-actin and CysLTR1/β-actin ratios and decreased the phosphorylation levels of AP-1 subunits (c-Fos, c-Jun and p38-MAP kinase, while increasing the detection of the ALX/FPR2 receptor. Moreover, various pharmacological agents revealed the blunting effects of RvD2 on LTD4 or TNF-α induced hyper-responsiveness. Combined treatment with 300 nM RvD2 and 1 μM WRW4 (an ALX/FPR2 receptor inhibitor blunted the pro-resolving and broncho-modulatory effects of RvD2. The present data provide new evidence regarding the role of RvD2 in a human model of airway inflammation and hyperrresponsiveness.

  2. Effects of d-norgestrel on lipid metabolism in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Khokha, R.


    The effects of the progestin d-norgestrel (d-Ng) on lipid and lipoprotein metabolism and elucidate its mechanism of action using the rat as the experimental model were investigated. d-Ng fed to female rats (18 days) in conventional doses, significantly lowered the plasma total and very low density lipoprotein (VLDL)-triglycerides. In contrast, the plasma total and low density lipoprotein (LDL)-cholesterol rose significantly. The triglyceride synthesis was studied using isolated rate hepatocytes. d-Ng (0.1 mM), in the presence of 0.1% dimethylsulfoxide concentration of the medium, significantly inhibited the incorporation of both (9,10-/sup 3/H) palmitate and (U-/sup 14/C) glycerol into triglycerides synthesized and triglycerides released by the hepatocytes. The inhibition of triglyceride synthesis by d-Ng was dose-dependent. Further studies of the effect of d-Ng on the rate limiting enzymes of triglyceride synthesis showed a significant reduction in the specific activity of hepatic glycerol phosphate acyltransferase (GPAT) and phosphatidic acid aqueous dependent phosphatidic acid phosphatase (PAPase) specifically in the microsomes. However, the specific activity of mitochondrial GPAT and phosphatidic acid membrane bound dependent PAPase in microsomes as well as cytosol remained unchanged. These findings suggest that d-Ng acts by inhibiting specifically the hepatic lipogenic enzymes in the microsomes. This subsequently reduces the triglyceride synthesis and secretion by the liver resulting in lower plasma and VLDL triglycerides levels in d-Ng-treated rats.

  3. Elderly with proximal hip fracture present significantly lower levels of 25-hydroxyvitamin D

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    Marcelo Teodoro Ezequiel Guerra

    Full Text Available ABSTRACT OBJECTIVE: To compare serum 25-hydroxyvitamin D (25[OH]D levels, a serum marker of vitamin D3, between patients with and without proximal hip fracture. METHODS: This was a case-control study in which serum samples of 25(OHD were obtained from 110 proximal hip fracture inpatients and 231 control patients without fractures, all over 60 years of age. Levels of 25(OHD lower than or equal to 20 ng/mL were considered deficient; from 21 ng/mL to 29 ng/mL, insufficient; and above 30 ng/mL, sufficient. Sex, age, and ethnicity were considered for association with the study groups and 25(OHD levels. RESULTS: Patients with proximal hip fracture had significantly lower serum 25(OHD levels (21.07 ng/mL than controls (28.59 ng/mL; p = 0.000. Among patients with proximal hip fracture, 54.5% had deficient 25(OHD levels, 27.2% had insufficient levels, and only 18.2% had sufficient levels. In the control group, 30.3% of patients had deficient 25(OHD levels, 30.7% had insufficient levels, and 38.9% had sufficient levels. Female patients had decreased serum 25(OHD levels both in the fracture group and in the control group (19.50 ng/mL vs. 26.94 ng/mL; p = 0.000 when compared with male patients with and without fracture (25.67 ng/mL vs. 33.74 ng/mL; p = 0.017. Regarding age, there was a significant association between 25(OHD levels and risk of fracture only for the age groups 71-75 years and above 80 years. CONCLUSION: Patients with proximal hip fracture had significantly decreased serum 25(OHD levels when compared with the control group. Female patients had significantly lower serum 25(OHD levels in both groups.

  4. Production and characterization of a murine monoclonal IgM antibody to human C1q receptor (C1qR)

    International Nuclear Information System (INIS)

    Ghebrehiwet, B.


    A hybridoma cell line that produces a monoclonal antibody (MAb) to cell surface C1q receptor (C1qr) has been produced by fusion of the P3 x 63-Ag8.653 mouse myeloma cell line with the spleen cells of a CD-1 mouse that had been hyperimmunized with viable Raji cell suspensions (5 x 10 7 cells/inoculum). This MAb, designated II1/D1, is an IgM antibody with lambda-light chain specificity. Radiolabeled or unlabeled, highly purified II1/D1 was used to determine that: a) this antibody competes for C1q binding sites on C1qR-bearing cells; b) the molecule recognized by this MAb is the C1qR; and c) cells that are known to bind C1q also bind II1/D1 in a specific manner. Western blot analysis of solubilized Raji, or U937 cell membranes, showed that the 125 I-MAb detected a major protein band of approximately 85000 m.w. in its unreduced state, indicating that the C1qR is similar, if not identical, in both types of cells. Analyses of 125 I-II/D1 binding experiments revealed that the antibody bound to Raji cells or u937 cells in a specific manner. Uptake of the antibody was saturable, with equilibrium virtually attained within 35 min. Scatchard analysis of the binding data using the intact MAb suggests that the affinity constant K/sub D/ is 2.9 x 10 -10 M, and at apparent saturation, 24.6 ng of the antibody were bound per 2 x 10 6 cells, giving an estimated 7.8 x 10 3 antibody molecules bound per cell. That the II1/D1 antibody is specifically directed to the C1q was further evidenced by an ELISA in which the ability of C1qR-bearing cells to bind the MAb was abrogated by c-C1q in a specific dose-dependent manner

  5. Molecular magnetism of M6 hexagon ring in D(3d) symmetric [(MCl)6(XW9O33)2](12-) (M = Cu(II) and Mn(II), X = Sb(III) and As(III)). (United States)

    Yamase, Toshihiro; Ishikawa, Hirofumi; Abe, Hiroko; Fukaya, Keisuke; Nojiri, Hiroyuki; Takeuchi, Hideo


    Ferromagnetic [n-BuNH(3)](12)[(CuCl)(6)(SbW(9)O(33))(2)]·6H(2)O (1) and antiferromagnetic [n-BuNH(3)](12)[(MnCl)(6)(AsW(9)O(33))(2)]·6H(2)O (4) have been synthesized and structurally and magnetically characterized. Two complexes are structural analogues of [n-BuNH(3)](12)[(CuCl)(6)(AsW(9)O(33))(2)]·6H(2)O (2) and [n-BuNH(3)](12)[(MnCl)(6)(SbW(9)O(33))(2)]·6H(2)O (3) with their ferromagnetic interactions, first reported by us in 2006. (1) When variable temperature (T) direct current (dc) magnetic susceptibility (χ(M)) data are analyzed with the isotropic exchange Hamiltonian for the magnetic exchange interactions, χ(M)T vs T curves fitted by a full matrix diagonalization (for 1) and by the Kambe vector coupling method/Van Vleck's approximation (for 4) yield J = +29.5 and -0.09 cm(-1) and g = 2.3 and 1.9, respectively. These J values were significantly distinguished from +61.0 and +0.14 cm(-1) for 2 and 3, respectively. The magnetization under the pulsed field (up to 10(3) T/s) at 0.5 K exhibits hysteresis loops in the adiabatic process, and the differential magnetization (dM/dB) plots against the pulsed field display peaks characteristic of resonant quantum tunneling of magnetization (QTM) at Zeeman crossed fields, indicating single-molecule magnets for 1-3. High-frequency ESR (HFESR) spectroscopy on polycrystalline samples provides g(∥) = 2.30, g(⊥) = 2.19, and D = -0.147 cm(-1) for 1 (S = 3 ground state), g(∥) = 2.29, g(⊥) = 2.20, and D = -0.145 cm(-1) for 2 (S = 3), and g(∥) = 2.03 and D = -0.007 cm(-1) for 3 (S = 15). An attempt to rationalize the magnetostructural correlation among 1-4, the structurally and magnetically modified D(3d)-symmetric M (=Cu(II) and Mn(II))(6) hexagons sandwiched by two diamagnetic α-B-[XW(9)O(33)](9-) (X = Sb(III) and As(III)) ligands through M-(μ(3)-O)-W linkages, is made. The strongest ferromagnetic coupling for the Cu(6) hexagon of 2, the structure of which approximately provides the Cu(6)(μ(3)-O)(12

  6. Differential effects of central injections of D1 and D2 receptor agonists and antagonists on male sexual behavior in Japanese quail. (United States)

    Kleitz-Nelson, H K; Cornil, C A; Balthazart, J; Ball, G F


    A key brain site in the control of male sexual behavior is the medial pre-optic area (mPOA) where dopamine stimulates both D1 and D2 receptor subtypes. Research completed to date in Japanese quail has only utilized systemic injections and therefore much is unknown about the specific role played by dopamine in the brain and mPOA in particular. The present study investigated the role of D1 and D2 receptors on male sexual behavior by examining how intracerebroventricular injections and microinjections into the mPOA of D1 and D2 agonists and antagonists influenced appetitive and consummatory aspects of sexual behavior in male quail. Experiments 1 and 2 investigated the effects of intracerebroventricular injections at three doses of D1 or D2 agonists and antagonists. The results indicated that D1 receptors facilitated consummatory male sexual behavior, whereas D2 receptors inhibited both appetitive and consummatory behaviors. Experiment 3 examined the effects of the same compounds specifically injected in the mPOA and showed that, in this region, both receptors stimulated male sexual behaviors. Together, these data indicated that the stimulatory action of dopamine in the mPOA may require a combined activation of D1 and D2 receptors. Finally, the regulation of male sexual behavior by centrally infused dopaminergic compounds in a species lacking an intromittent organ suggested that dopamine action on male sexual behavior does not simply reflect the modulation of genital reflexes due to general arousal, but relates to the central control of sexual motivation. Together, these data support the claim that dopamine specifically regulates male sexual behavior.

  7. Analytical and clinical evaluation of the new Fujirebio Lumipulse®G non-competitive assay for 25(OH)-vitamin D and three immunoassays for 25(OH)D in healthy subjects, osteoporotic patients, third trimester pregnant women, healthy African subjects, hemodialyzed and intensive care patients. (United States)

    Cavalier, Etienne; Lukas, Pierre; Bekaert, Anne-Catherine; Peeters, Stéphanie; Le Goff, Caroline; Yayo, Eric; Delanaye, Pierre; Souberbielle, Jean-Claude


    In this study, we provide a short analytical evaluation of the new Fujirebio Lumipulse®G non-competitive immunoassay for 25(OH)D. Clinical performance was compared with three commercial competitive automated immunoassays against a Vitamin D Standardization Program (VDSP)-traceable liquid chromatography-tandem mass spectrometry (LC-MS/MS) in six different clinically relevant populations. Lumipulse®G 25(OH)D precision, measurement uncertainty, recovery, limit of quantification were assessed, as well as 25(OH)D2 and C3-epimer recovery. For method comparison, 250 serum samples obtained in healthy Caucasians and Africans, osteoporotic, hemodialyzed and intensive care patients and 3rd trimester pregnant women were analyzed by all methods. Correlation was studied using Passing-Bablok and Bland-Altman analysis. Concordance correlation coefficient (CCC) was calculated to evaluate agreement between immunoassays and the LC-MS/MS. The Lumipulse®G 25(OH)D assay presented interesting analytical features and showed excellent correlation to the LC-MS/MS results (y=1.00×-1.35 ng/mL), as obtained in healthy Caucasian individuals. In the other special populations, Lumipulse®G presented a concordance with LC-MS/MS which was generally higher than competitors, even if all methods significantly under-recovered 25(OH)D in hemodialyzed patients. Intra-assay CV ranged from 12.1% at 9.6 ng/mL to 2.1% at 103.7 ng/mL and inter-assay CV ranged from 16.2 to 3.7% at the same concentrations, respectively. Measurement uncertainty, with a probability of 95%, were respectively 33.1 and 7.6% at these concentrations. LOQ was found to be at 4.6 ng/mL. Mean (95% CI) 25(OH)D2 revovery was 77% (74-81) and no cross-reactivity was observed with C3-epimer. Fujirebio Lumipulse®G 25-OH Vitamin D Total assay is therefore considered suitable for assessment of vitamin D status in clinical routine.

  8. [H2en]2{La2M(SO4)6(H2O)2} (M=Co, Ni): First organically templated 3d-4f mixed metal sulfates

    International Nuclear Information System (INIS)

    Yuan Yanping; Wang Ruiyao; Kong Deyuan; Mao Jianggao; Clearfield, Abraham


    The first organically templated 3d-4f mixed metal sulfates, [H 2 en] 2 {La 2 M(SO 4 ) 6 (H 2 O) 2 } (M=Co 1, Ni 2) have been synthesized and structurally determined from non-merohedrally twinned crystals. The two compounds are isostructural and their structures feature a three-dimensional anionic network formed by the lanthanum(III) and nickel(II) ions bridged by sulfate anions. The La(III) ions in both compounds are 10-coordinated by four sulfate anions in bidentate chelating fashion, and two sulfate anions in a unidentate fashion. The transition metal(II) ion is octahedrally coordinated by six oxygens from four sulfate anions and two aqua ligands. The doubly protonated enthylenediamine cations are located at the tunnels formed by 8-membered rings (four La and four sulfate anions)

  9. Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages. (United States)

    Soldano, Stefano; Pizzorni, Carmen; Paolino, Sabrina; Trombetta, Amelia Chiara; Montagna, Paola; Brizzolara, Renata; Ruaro, Barbara; Sulli, Alberto; Cutolo, Maurizio


    Alternatively activated (M2) macrophages are phenotypically characterized by the expression of specific markers, mainly macrophage scavenger receptors (CD204 and CD163) and mannose receptor-1 (CD206), and participate in the fibrotic process by over-producing pro-fibrotic molecules, such as transforming growth factor-beta1 (TGFbeta1) and metalloproteinase (MMP)-9. Endothelin-1 (ET-1) is implicated in the fibrotic process, exerting its pro-fibrotic effects through the interaction with its receptors (ETA and ETB). The study investigated the possible role of ET-1 in inducing the transition from cultured human macrophages into M2 cells. Cultured human monocytes (THP-1 cell line) were activated into macrophages (M0 macrophages) with phorbol myristate acetate and subsequently maintained in growth medium (M0-controls) or treated with either ET-1 (100nM) or interleukin-4 (IL-4, 10ng/mL, M2 inducer) for 72 hours. Similarly, primary cultures of human peripheral blood monocyte (PBM)-derived macrophages obtained from healthy subjects, were maintained in growth medium (untreated cells) or treated with ET-1 or IL-4 for 6 days. Both M0 and PBM-derived macrophages were pre-treated with ET receptor antagonist (ETA/BRA, bosentan 10-5M) for 1 hour before ET-1 stimulation. Protein and gene expression of CD204, CD206, CD163, TGFbeta1 were analysed by immunocytochemistry, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Gene expression of interleukin(IL)-10 and macrophage derived chemokine (CCL-22) was evaluated by qRT-PCR. MMP-9 production was investigated by gel zymography. ET-1 significantly increased the expression of M2 phenotype markers CD204, CD206, CD163, IL-10 and CCL-22, and the production of MMP-9 in both cultures of M0 and PBM-derived macrophages compared to M0-controls and untreated cells. In cultured PBM-derived macrophages, ET-1 increased TGFbeta1 protein and gene expression compared to untreated cells. The ET-1-mediated effects were

  10. Development of 99mTc-labelled the d,1-diasteroisomer of HM-PAO for cerebral blood flow imaging

    International Nuclear Information System (INIS)

    Lun Xiao.


    The d,1-diastereoisomer of hexamethyl propyleneamine oxime (HM-PAO) was selected as the preferred ligand for Tc-99m as a radiotracer for cerebral perfusion imaging. Further improvement of the synthesis and isolation method of HM-PAO resulted in pure d,1-HM-PAO and pure meso-HM-PAO. The neutral, lipophilic Tc-99m complexes of d,1-HM-PAO and meso-HM-PAO were formed in high yield by stannous reduction of Mo-99/Tc-99m generator eluate, respectively. Two minutes following i.v. administration of Tc-99m-d,1-HM-PAO in mice, 2.24% of the injected dose appears in the brain. Little washout of the tracer is observed up to 24-hour post injection. Two minutes following i.v. administration of Tc-99m-meso-HM-PAO in mice, 1.9% of the injected dose appears in the brain. The radioactivity of Tc-99m-meso-HM-PAO declined faster than that of Tc-99m-d,1-HM-PAO did in the brain up to 24-hour post injection. 12 refs, 5 figs, 5 tabs

  11. Exploring the Nature of Silicon-Noble Gas Bonds in H3SiNgNSi and HSiNgNSi Compounds (Ng = Xe, Rn

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    Sudip Pan


    Full Text Available Ab initio and density functional theory-based computations are performed to investigate the structure and stability of H3SiNgNSi and HSiNgNSi compounds (Ng = Xe, Rn. They are thermochemically unstable with respect to the dissociation channel producing Ng and H3SiNSi or HSiNSi. However, they are kinetically stable with respect to this dissociation channel having activation free energy barriers of 19.3 and 23.3 kcal/mol for H3SiXeNSi and H3SiRnNSi, respectively, and 9.2 and 12.8 kcal/mol for HSiXeNSi and HSiRnNSi, respectively. The rest of the possible dissociation channels are endergonic in nature at room temperature for Rn analogues. However, one three-body dissociation channel for H3SiXeNSi and one two-body and one three-body dissociation channels for HSiXeNSi are slightly exergonic in nature at room temperature. They become endergonic at slightly lower temperature. The nature of bonding between Ng and Si/N is analyzed by natural bond order, electron density and energy decomposition analyses. Natural population analysis indicates that they could be best represented as (H3SiNg+(NSi− and (HSiNg+(NSi−. Energy decomposition analysis further reveals that the contribution from the orbital term (ΔEorb is dominant (ca. 67%–75% towards the total attraction energy associated with the Si-Ng bond, whereas the electrostatic term (ΔEelstat contributes the maximum (ca. 66%–68% for the same in the Ng–N bond, implying the covalent nature of the former bond and the ionic nature of the latter.

  12. Localisation of NG2 immunoreactive neuroglia cells in the rat locus coeruleus and their plasticity in response to stress

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    Mohsen eSeifi


    Full Text Available The locus coeruleus (LC nucleus modulates adaptive behavioural responses to stress and dysregulation of LC neuronal activity is implicated in stress-induced mental illnesses. The LC is composed primarily of noradrenergic neurons together with various glial populations. A neuroglia cell-type largely unexplored within the LC is the NG2 cell. NG2 cells serve primarily as oligodendrocyte precursor cells throughout the brain. However, some NG2 cells are in synaptic contact with neurons suggesting a role in information processing. The aim of this study was to neurochemically and anatomically characterise NG2 cells within the rat LC. Furthermore, since NG2 cells have been shown to proliferate in response to traumatic brain injury, we investigated whether such NG2 cells plasticity also occurs in response to emotive insults such as stress. Immunohistochemistry and confocal microscopy revealed that NG2 cells were enriched within the pontine region occupied by the LC. Close inspection revealed that a sub-population of NG2 cells were located within unique indentations of LC noradrenergic somata and were immunoreactive for the neuronal marker NeuN whilst NG2 cell processes formed close appositions with clusters immunoreactive for the inhibitory synaptic marker proteins gephyrin and the GABA-A receptor alpha3-subunit, on noradrenergic dendrites. In addition, LC NG2 cell processes were decorated with vesicular glutamate transporter 2 immunoreactive puncta. Finally, ten days of repeated restraint stress significantly increased the density of NG2 cells within the LC. The study demonstrates that NG2 IR cells are integral components of the LC cellular network and they exhibit plasticity as a result of emotive challenges.

  13. Association of Vitamin D Deficiency and Thyroid Function in Postmenopausal Women

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    Mitra Niafar


    Full Text Available Pupose: Although there are reports of vitamin D (VitD insufficiency in immune-mediated hypothyroidism, an association between VitD and thyroid-stimulating hormone (TSH levels has yet to be shown. We aim to examine VitD and TSH levels among postmenopausal women, as both conditions are more prevalent in elderly women. Methods: The clinic records of postmenopausal women during their routine maintenance visits were reviewed. All patients were examined for the symptoms related to thyroid function and osteoporosis. Participants were divided into three subgroups according to their TSH levels (below 4.0 mIU/L. Patient characteristics and VitD levels were compared between these subgroups. Multivariate linear regression model was constructed using serum VitD and serum TSH as the dependent variables to identify factors independently associated with these laboratory values. Results: Two-hundred and nighty nine postmenopausal women were included. Average age was 62.2±7.5 years old. VitD was insufficient (10-30 ng/mL in 12.0% and deficient (<10 ng/mL in 60.9% of the participants. In 11.3%, TSH was low and in 7.6% of women, TSH was high, while the remaining 80.1%, had normal TSH levels. Subjects with low TSH had significantly higher VitD concentrations (34.2±29.1 ng/mL compared to the other two groups (P-value: 0.039. In multivariate regression analysis, TSH was not a contributing factor, as age was the only significant predictor of VitD levels. Meanwhile, no predictor (including age and VitD was identified for TSH levels in linear regression analysis. Conclusion: Age was the only independent predictor of serum VitD in this study population. Though suppressed TSH was associated with higher VitD levels, the association was not linear between TSH and VitD in postmenopausal women.

  14. Inhibitory effects of aspirin-triggered resolvin D1 on spinal nociceptive processing in rat pain models. (United States)

    Meesawatsom, Pongsatorn; Burston, James; Hathway, Gareth; Bennett, Andrew; Chapman, Victoria


    Harnessing the actions of the resolvin pathways has the potential for the treatment of a wide range of conditions associated with overt inflammatory signalling. Aspirin-triggered resolvin D1 (AT-RvD1) has robust analgesic effects in behavioural models of pain; however, the potential underlying spinal neurophysiological mechanisms contributing to these inhibitory effects in vivo are yet to be determined. This study investigated the acute effects of spinal AT-RvD1 on evoked responses of spinal neurones in vivo in a model of acute inflammatory pain and chronic osteoarthritic (OA) pain and the relevance of alterations in spinal gene expression to these neurophysiological effects. Pain behaviour was assessed in rats with established carrageenan-induced inflammatory or monosodium iodoacetate (MIA)-induced OA pain, and changes in spinal gene expression of resolvin receptors and relevant enzymatic pathways were examined. At timepoints of established pain behaviour, responses of deep dorsal horn wide dynamic range (WDR) neurones to transcutaneous electrical stimulation of the hind paw were recorded pre- and post direct spinal administration of AT-RvD1 (15 and 150 ng/50 μl). AT-RvD1 (15 ng/50 μl) significantly inhibited WDR neurone responses to electrical stimuli at C- (29 % inhibition) and Aδ-fibre (27 % inhibition) intensities. Both wind-up (53 %) and post-discharge (46 %) responses of WDR neurones in carrageenan-treated animals were significantly inhibited by AT-RvD1, compared to pre-drug response (p < 0.05). These effects were abolished by spinal pre-administration of a formyl peptide receptor 2 (FPR2/ALX) antagonist, butoxy carbonyl-Phe-Leu-Phe-Leu-Phe (BOC-2) (50 μg/50 μl). AT-RvD1 did not alter evoked WDR neurone responses in non-inflamed or MIA-treated rats. Electrophysiological effects in carrageenan-inflamed rats were accompanied by a significant increase in messenger RNA (mRNA) for chemerin (ChemR23) receptor and 5-lipoxygenase

  15. Impact of Three Doses of Vitamin D3 on Serum 25(OH)D Deficiency and Insufficiency in At-Risk Schoolchildren. (United States)

    Sacheck, Jennifer M; Van Rompay, Maria I; Chomitz, Virginia R; Economos, Christina D; Eliasziw, Misha; Goodman, Elizabeth; Gordon, Catherine M; Holick, Michael F


    We investigated the daily dose of vitamin D needed to achieve serum 25-hydroxyvitamin D [25(OH)D] sufficiency among schoolchildren at risk for deficiency. The Daily D Health Study was a randomized double-blind vitamin D supplementation trial among racially/ethnically diverse schoolchildren (n = 685) in the northeastern United States. Children were supplemented with vitamin D3 at 600, 1000, or 2000 IU/d for 6 months. Measurements included serum 25(OH)D at baseline (October to December), 3 months (January to March), 6 months (April to June), and 12 months (6 months after supplementation). At baseline, mean ± standard deviation serum 25(OH)D level was 22.0 ± 6.8 ng/mL, with 5.5% severely vitamin D deficient (D were found among black (17.9 ± 6.7 ng/mL) and Asian children (18.9 ± 4.8 ng/mL), with no baseline differences by weight status. Serum 25(OH)D increased over 6 months in all three dose groups. The 2000 IU/d group achieved a higher mean serum 25(OH)D level than the other two dose groups (33.1 vs 26.3 and 27.5 ng/mL; P D at 12 months. Children at risk for vitamin D deficiency benefited from daily sustained supplementation of 2000 IU/d compared with lower doses closer to the current recommended daily allowance for vitamin D intake. This benefit occurred over the winter months, when serum 25(OH)D level tend to fall. Copyright © 2017 Endocrine Society

  16. Protein phosphatase magnesium-dependent 1δ (PPM1D mRNA expression is a prognosis marker for hepatocellular carcinoma.

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    Guang-Bing Li

    Full Text Available Protein phosphatase magnesium-dependent 1δ (PPM1D is an oncogene, overexpressed in many solid tumors, including ovarian cancer and breast cancer. The current study examined the expression and the prognostic value of PPM1D mRNA in human hepatocellular carcinoma (HCC.Total RNA was extracted from 86 HCC and paired non-cancerous liver tissues. PPM1D mRNA expression was determined by real-time quantitative reverse transcriptase-polymerase chain reaction (qPCR. Immunohistochemistry assay was used to verify the expression of ppm1d protein in the HCC and non-cancerous liver tissues. HCC patients were grouped according to PPM1D mRNA expression with the average PPM1D mRNA level in non-cancerous liver tissue samples as the cut-off. Correlations between clinicopathologic variables, overall survival and PPM1D mRNA expression were analyzed.PPM1D mRNA was significantly higher in HCC than in the paired non-cancerous tissue (p<0.01. This was confirmed by ppm1d staining. 56 patients were classified as high expression group and the other 30 patients were categorized as low expression group. There were significant differences between the two groups in term of alpha-fetoprotein (α-FP level (p<0.01, tumor size (p<0.01, TNM stage (p<0.01, recurrence incidence (p<0.01 and family history of liver cancer (p<0.01. The current study failed to find significant differences between the two groups in the following clinical characteristics: age, gender, portal vein invasion, lymphnode metastasis, hepatitis B virus (HBV infection and alcohol intake. Survival time of high expression group was significantly shorter than that of low expression group (median survival, 13 months and 32 months, respectively, p<0.01.Up-regulation of PPM1D mRNA was associated with progressive pathological feature and poor prognosis in HCC patients. PPM1D mRNA may serve as a prognostic marker in HCC.

  17. Correction of vitamin D deficiency using sublingually administered vitamin D2 in a Crohn's disease patient with mal-absorption and a new ileostomy. (United States)

    McCullough, Patrick; Heaney, Robert


    Vitamin D deficiency has been shown to be associated with many adverse health problems. Studies have shown that patients with Crohn's disease who have low vitamin D levels have a poorer quality of life than those with more adequate levels. It has also been shown that patients with mal-absorption problems have a difficult time achieving normal vitamin D levels in spite of aggressive supplementation, and that exposure to UVB radiation may be the most effective treatment option for these patients. We present a case in which 25-hydroxyvitamin D levels were normalized within 2 weeks in a severely vitamin D deficient patient with Crohn's disease with mal-absorption and a new ileostomy, utilizing sublingually administered vitamin D2. A 58 year-old white female was admitted with a new ileostomy following partial bowel resection due to complications from Crohn's disease. She was found to be severely vitamin D deficient at the time of admission, with a level of 6.1ng/ml on hospital day 3. Her treatment with vitamin D was delayed for a few days. She was initially treated with 5000 units of vitamin D3 orally twice a day for 3days (days 7-10). After discussion with the patient and obtaining her consent, vitamin D3 was stopped, and she was then treated with a total of 8 doses of 50,000 units of vitamin D2 administered sublingually. She was given the first 3 doses on alternating days (days 11, 13, 15), and then 5 more doses on consecutive days (days 17-21). The rise in her 25-hydroxyvitamin D level in response to treatment with sublingual vitamin D2 was significant. On day 10, after receiving 3days of orally administered vitamin D3, her level was 9.8ng/ml. One week later, after receiving 3 sublingual doses of vitamin D2, it rose to 20.3ng/ml. It was then measured on alternating days twice over the next 4days, and it rose to 45.5ng/ml, and then to 47.4ng/ml on the day of discharge to home. The major finding of this study is that sublingual administration of vitamin D2 appears to

  18. 25-Hydroxyvitamin D Status of Healthy, Low-Income, Minority Children in Atlanta, Georgia (United States)

    Cole, Conrad R.; Grant, Frederick K.; Tangpricha, Vin; Swaby-Ellis, E. Dawn; Smith, Joy L.; Jacques, Anne; Chen, Huiping; Schleicher, Rosemary L.; Ziegler, Thomas R.


    OBJECTIVES The goals were to determine the prevalence of vitamin D deficiency among minority children in a southern US city, to examine differences in serum 25-hydroxyvitamin D levels between non-Hispanic black and Hispanic children, and to determine dietary sources of vitamin D. METHODS Low-income, minority children (N = 290; mean age: 2.5 ± 1.2 years) were recruited during well-child clinic visits. Serum 25-hydroxyvitamin D and calcium levels were measured and dietary information was assessed. RESULTS The mean 25-hydroxyvitamin D3 level was 26.2 ± 7.6 ng/mL, whereas 25-hydroxyvitamin D2 was not detected. Overall, 22.3% of children had deficient serum 25-hydroxyvitamin D3 levels (≤20 ng/mL), 73.6% had less-than-optimal serum 25-hydroxyvitamin D levels (≤30 ng/mL), and 1.4% had low serum calcium levels (≤9 mg/dL). A significantly larger proportion of non-Hispanic black children, compared with Hispanic children, had vitamin D deficiency (26% vs 18%; P<.05). Age and season of recruitment were significantly associated with vitamin D deficiency and low serum calcium levels. Older children (≥3 years) were less likely to have vitamin D deficiency (odds ratio [OR]: 0.89 [95% confidence interval [CI]: 0.81– 0.96]; P < .001). Study enrollment during spring and summer reduced the likelihood of vitamin D deficiency by ~20% (spring, OR: 0.85 [95% CI: 0.73– 0.98]; P = .03; summer, OR: 0.82 [95% CI: 0.73– 0.92]; P < .01). Fortified milk provided most dietary vitamin D (62%), with Hispanic children reporting greater intake. CONCLUSIONS Suboptimal vitamin D status was common among apparently healthy, low-income, minority children. Age and season were significant predictors of vitamin D deficiency. PMID:20351012

  19. Intrastriatal administration of botulinum neurotoxin A normalizes striatal D2 R binding and reduces striatal D1 R binding in male hemiparkinsonian rats. (United States)

    Wedekind, Franziska; Oskamp, Angela; Lang, Markus; Hawlitschka, Alexander; Zilles, Karl; Wree, Andreas; Bauer, Andreas


    Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1ng BoNT-A, while the others received vehicle (n = 7). All animals were tested for asymmetric motor behavior (apomorphine-induced rotations and forelimb usage) and for striatal expression of dopamine receptors and transporters (D 1 R, D 2 R, and DAT). The striatal D 2 R availability was also quantified longitudinally (1.5, 3, and 5 months after intervention) in 5 animals per treatment group. The 6-OHDA lesion alone induced a unilateral PD-like phenotype and a 13% increase of striatal D 2 R. BoNT-A treatment reduced the asymmetry in both apomorphine-induced rotational behavior and D 2 R expression, with the latter returning to normal values 5 months after intervention. D 1 R expression was significantly reduced, while DAT concentrations showed no alteration. Independent of the treatment, higher interhemispheric symmetry in raclopride binding to D 2 R was generally associated with reduced forelimb akinesia. Our findings indicate that striatal BoNT-A treatment diminishes motor impairment and induces changes in D 1 and D 2 binding site density in the 6-OHDA rat model of PD. © 2017 Wiley Periodicals, Inc.

  20. Group I mGluR antagonist rescues the deficit of D1-induced LTP in a mouse model of fragile X syndrome

    Directory of Open Access Journals (Sweden)

    Xu Zhao-Hui


    Full Text Available Abstract Background Fragile X syndrome (FXS is caused by the absence of the mRNA-binding protein Fragile X mental retardation protein (FMRP, encoded by the Fmr1 gene. Overactive signaling by group 1 metabotropic glutamate receptor (Grp1 mGluR could contribute to slowed synaptic development and other symptoms of FXS. Our previous study has identified that facilitation of synaptic long-term potentiation (LTP by D1 receptor is impaired in Fmr1 knockout (KO mice. However, the contribution of Grp1 mGluR to the facilitation of synaptic plasticity by D1 receptor stimulation in the prefrontal cortex has been less extensively studied. Results Here we demonstrated that DL-AP3, a Grp1 mGluR antagonist, rescued LTP facilitation by D1 receptor agonist SKF81297 in Fmr1KO mice. Grp1 mGluR inhibition restored the GluR1-subtype AMPA receptors surface insertion by D1 activation in the cultured Fmr1KO neurons. Simultaneous treatment of Grp1 mGluR antagonist with D1 agonist recovered the D1 receptor signaling by reversing the subcellular redistribution of G protein-coupled receptor kinase 2 (GRK2 in the Fmr1KO neurons. Treatment of SKF81297 alone failed to increase the phosphorylation of NR2B-containing N-methyl D-aspartate receptors (NMDARs at Tyr-1472 (p-NR2B-Tyr1472 in the cultures from KO mice. However, simultaneous treatment of DL-AP3 could rescue the level of p-NR2B-Tyr1472 by SKF81297 in the cultures from KO mice. Furthermore, behavioral tests indicated that simultaneous treatment of Grp1 mGluR antagonist with D1 agonist inhibited hyperactivity and improved the learning ability in the Fmr1KO mice. Conclusion The findings demonstrate that mGluR1 inhibition is a useful strategy to recover D1 receptor signaling in the Fmr1KO mice, and combination of Grp1 mGluR antagonist and D1 agonist is a potential drug therapy for the FXS.

  1. Cocaine Inhibits Dopamine D2 Receptor Signaling via Sigma-1-D2 Receptor Heteromers (United States)

    Navarro, Gemma; Moreno, Estefania; Bonaventura, Jordi; Brugarolas, Marc; Farré, Daniel; Aguinaga, David; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carmen; Ferre, Sergi


    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

  2. Sex differences, learning flexibility, and striatal dopamine D1 and D2 following adolescent drug exposure in rats (United States)

    Izquierdo, Alicia; Pozos, Hilda; De La Torre, Adrianna; DeShields, Simone; Cevallos, James; Rodriguez, Jonathan; Stolyarova, Alexandra


    Corticostriatal circuitry supports flexible reward learning and emotional behavior from the critical neurodevelopmental stage of adolescence through adulthood. It is still poorly understood how prescription drug exposure in adolescence may impact these outcomes in the long-term. We studied adolescent methylphenidate (MPH) and fluoxetine (FLX) exposure in rats and their impact on learning and emotion in adulthood. In Experiment 1, male and female rats were administered MPH, FLX, or saline (SAL), and compared with methamphetamine (mAMPH) treatment beginning in postnatal day (PND) 37. The rats were then tested on discrimination and reversal learning in adulthood. In Experiment 2, animals were administered MPH or SAL also beginning in PND 37 and later tested in adulthood for anxiety levels. In Experiment 3, we analyzed striatal dopamine D1 and D2 receptor expression in adulthood following either extensive learning (after Experiment 1) or more brief emotional measures (after Experiment 2). We found sex differences in discrimination learning and attenuated reversal learning after MPH and only sex differences in adulthood anxiety. In learners, there was enhanced striatal D1, but not D2, after either adolescent MPH or mAMPH. Lastly, also in learners, there was a sex x treatment group interaction for D2, but not D1, driven by the MPH-pretreated females, who expressed significantly higher D2 levels compared to SAL. These results show enduring effects of adolescent MPH on reversal learning in rats. Developmental psychostimulant exposure may interact with learning to enhance D1 expression in adulthood, and affect D2 expression in a sex-dependent manner. PMID:27091300

  3. Reaction of Br/sub 3/. /sup 2 -/ with 2-deoxy-D-ribose. A preferred attack at C-1

    Energy Technology Data Exchange (ETDEWEB)

    Parsons, B J; Schulte-Frohlinde, D; von Sonntag, C [Max-Planck-Institut fuer Kohlenforschung, Muelheim an der Ruhr (Germany, F.R.). Inst. fuer Strahlenchemie


    In the photolysis of 5-bromouracil containing DNA Br atoms are expected intermediates. In order to evaluate the possible site of attack of the Br atom at the sugar moiety of DNA the reaction of 2-deoxy-D-Ribose with the Br atom (complexed with two bromide ions) was investigated. Hydroxyl radicals generated by the radiolysis of N/sub 2/O saturated aqueous solutions were converted into Br/sub 3/./sup 2 -/-radicals by 1 M bromide ions. Br/sub 3/./sup 2 -/-reacts with 2-deoxy-D-ribose (k = 3.7 x 10/sup 4/M/sup -1/s/sup -1/, pulse radiolysis). The major product is 2-deoxy-D-erythro-pentonic acid (G = 2.4, ..gamma..-radiolysis). It is formed by hydrogen abstraction from C-1 and oxidation of this radical by other radicals. An alternative route via the radical at C-2 is neglible. It follows that Br/sub 3/./sup 2 -/ reacts preferentially at C-1 of 2-deoxy-D-ribose.

  4. Pulsed laser deposition of {CeO_2} and {Ce_{1-x}M_xO_2} (M = La, Zr): Application to insulating barrier in cuprate heterostructures (United States)

    Berger, S.; Contour, J.-P.; Drouet, M.; Durand, O.; Khodan, A.; Michel, D.; Régi, F.-X.


    SrTiO_3 had been often tentatively used as an insulating barrier for HT superconductor/insulator heterostructures. Unfortunately, the deposition of SrTiO_3 on the YBa_2Cu_3O_7 inverse interface results in a poor epitaxial regrowth producing a high roughness dislocated titanate layer. Taking into account the good matching with YBa_2Cu_3O_7 and LaAlO_3, CeO_2 and Ce_{1-x}M_xO_2 (M = La, Zr), epitaxial layers were grown by pulsed laser deposition on LaAlO_3 substrates and introduced into YBa_2Cu_3O_7 based heterostructures as insulating barrier. After adjusting the growth parameters from RHEED oscillations, epitaxial growth is achieved, the oxide crystal axes being rotated by 45^circ from those of the substrate. The surface roughness of 250 nm thick films is very low with a rms value lower than 0.5 nm over 1m^2. The YBa_2Cu_3O_7 layers of a YBa_2Cu_3O_7/CeO_2 /YBa_2Cu_3O_7 heterostructures grown using these optimized parameters show an independent resistive transition, when the thickness is larger than 25 nm, respectively at T_c_1 = 89.6;K and T_c_2 = 91.4;{K}. SrTiO3 est souvent utilisé comme barrière isolante dans des hétérostructures SIS de cuprates supraconducteurs, cependant les défauts générés lors de la croissance de ce titanate sur l'interface inverse de YBa2Cu3O7 conduisent à un matériau dont la qualité cristalline et les propriétés physiques sont médiocres. L'oxyde de cérium CeO2 est également une barrière isolante potentielle intéressante pour ces structures SIS basées sur YBa2Cu3O7 car cet oxyde cubique (a = 0,5411 nm, asqrt{2}/2 = 0,3825 nm) qui est peu désaccordé par rapport au plan ab du cuprate (Δ a/a = - 0,18 %, Δ b/a = 1,6 %) présente de plus un coefficient de dilatation thermique (10,6 × 10^{-6 circ}C^{-1}) très voisin de celui de YBa2Cu3O7 (13 × 10^{-6 circ}C^{-1}). Nous avons donc étudié l'épitaxie de CeO2 et des oxydes de type Ce{1-x}MxO2 (M = La, Zr) en ablation laser pulsée afin de définir des conditions de

  5. Main: 1M2Q [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1M2Q トウモロコシ Corn Zea mays L. Casein Kinase Ii, Alpha Chain Name=Ack2; Zea Mays Mole...cule: Casein Kinase Ii, Alpha Chain; Chain: A; Fragment: Catlytic Subunit; Synonym: Ckii; Engineered: Yes Tr...ansferase (Casein Kinase Ii, Alpha Chain) E.De Moliner, S.Sarno, S.Moro, G.Zagotto, G.Zanotti, L.A....=2-326.|PDB; 1M2Q; X-ray; A=2-328.|PDB; 1M2R; X-ray; A=2-328.|PDB; 1OM1; X-ray; A=1-332.|Mai

  6. Temperature-dependent Raman and ultraviolet photoelectron spectroscopy studies on phase transition behavior of VO{sub 2} films with M1 and M2 phases

    Energy Technology Data Exchange (ETDEWEB)

    Okimura, Kunio, E-mail:; Hanis Azhan, Nurul [Graduate School of Engineering, Tokai University, Hiratsuka 259-1292 (Japan); Hajiri, Tetsuya [UVSOR Facility, Institute for Molecular Science, Okazaki 444-8585 (Japan); Graduate School of Engineering, Nagoya University, Nagoya 464-8603 (Japan); Kimura, Shin-ichi [UVSOR Facility, Institute for Molecular Science, Okazaki 444-8585 (Japan); Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871 (Japan); Zaghrioui, Mustapha; Sakai, Joe [GREMAN, UMR 7347 CNRS, Université François Rabelais de Tours, Parc de Grandmont, 37200 Tours (France)


    Structural and electronic phase transitions behavior of two polycrystalline VO{sub 2} films, one with pure M1 phase and the other with pure M2 phase at room temperature, were investigated by temperature-controlled Raman spectroscopy and ultraviolet photoelectron spectroscopy (UPS). We observed characteristic transient dynamics in which the Raman modes at 195 cm{sup −1} (V-V vibration) and 616 cm{sup −1} (V-O vibration) showed remarkable hardening along the temperature in M1 phase film, indicating the rearrangements of V-V pairs and VO{sub 6} octahedra. It was also shown that the M1 Raman mode frequency approached those of invariant M2 peaks before entering rutile phase. In UPS spectra with high energy resolution of 0.03 eV for the M2 phase film, narrower V{sub 3d} band was observed together with smaller gap compared to those of M1 phase film, supporting the nature of Mott insulator of M2 phase even in the polycrystalline film. Cooperative behavior of lattice rearrangements and electronic phase transition was suggested for M1 phase film.

  7. 3D T2-weighted imaging to shorten multiparametric prostate MRI protocols. (United States)

    Polanec, Stephan H; Lazar, Mathias; Wengert, Georg J; Bickel, Hubert; Spick, Claudio; Susani, Martin; Shariat, Shahrokh; Clauser, Paola; Baltzer, Pascal A T


    To determine whether 3D acquisitions provide equivalent image quality, lesion delineation quality and PI-RADS v2 performance compared to 2D acquisitions in T2-weighted imaging of the prostate at 3 T. This IRB-approved, prospective study included 150 consecutive patients (mean age 63.7 years, 35-84 years; mean PSA 7.2 ng/ml, 0.4-31.1 ng/ml). Two uroradiologists (R1, R2) independently rated image quality and lesion delineation quality using a five-point ordinal scale and assigned a PI-RADS score for 2D and 3D T2-weighted image data sets. Data were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/area under the curve (AUC) analysis. Image quality was similarly good to excellent for 2D T2w (mean score R1, 4.3 ± 0.81; R2, 4.7 ± 0.83) and 3D T2w (mean score R1, 4.3 ± 0.82; R2, 4.7 ± 0.69), p = 0.269. Lesion delineation was rated good to excellent for 2D (mean score R1, 4.16 ± 0.81; R2, 4.19 ± 0.92) and 3D T2w (R1, 4.19 ± 0.94; R2, 4.27 ± 0.94) without significant differences (p = 0.785). ROC analysis showed an equivalent performance for 2D (AUC 0.580-0.623) and 3D (AUC 0.576-0.629) T2w (p > 0.05, respectively). Three-dimensional acquisitions demonstrated equivalent image and lesion delineation quality, and PI-RADS v2 performance, compared to 2D in T2-weighted imaging of the prostate. Three-dimensional T2-weighted imaging could be used to considerably shorten prostate MRI protocols in clinical practice. • 3D shows equivalent image quality and lesion delineation compared to 2D T2w. • 3D T2w and 2D T2w image acquisition demonstrated comparable diagnostic performance. • Using a single 3D T2w acquisition may shorten the protocol by 40%. • Combined with short DCE, multiparametric protocols of 10 min are feasible.

  8. Anti-NKG2D mAb

    DEFF Research Database (Denmark)

    Vadstrup, Kasper; Bendtsen, Flemming


    with a wide range of cell types and proteins involved. Natural Killer Group 2D (NKG2D) is an activating receptor constitutively expressed on human Natural Killer (NK), γδ T, mucosal-associated invariant T (MAIT), CD56⁺ T, and CD8⁺ T cells. Activation of NKG2D triggers cellular proliferation, cytokine...... production, and target cell killing. Research into the NKG2D mechanism of action has primarily been focused on cancer and viral infections where cytotoxicity evasion is a concern. In human inflammatory bowel disease (IBD) this system is less characterized, but the ligands have been shown to be highly...... expressed during intestinal inflammation and the following receptor activation may contribute to tissue degeneration. A recent phase II clinical trial showed that an antibody against NKG2D induced clinical remission of CD in some patients, suggesting NKG2D and its ligands to be of importance...

  9. Fibroblast Growth Factor-23 and Vitamin D Metabolism in Subjects with eGFR ≥60 ml/min/1.73 m². (United States)

    Nakatani, Shinya; Nakatani, Ayumi; Tsugawa, Naoko; Yamada, Shinsuke; Mori, Katsuhito; Imanishi, Yasuo; Ishimura, Eiji; Okano, Toshio; Inaba, Masaaki


    Fibroblast growth factor (FGF)-23 and parathyroid hormone (PTH) are both potent phosphaturic hormones. Since they exert opposite effects on vitamin D metabolism, the measurement of 3 vitamin D metabolites; 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and 24,25-dihydroxyvitamin D (24,25(OH)2D), allows the distinction of the effects of FGF-23 from those of PTH. The aim of this study was to elucidate which factor, FGF-23 or PTH, plays a more important role in the regulation of vitamin D metabolites in subjects with estimated glomerular filtration (eGFR) ≥60 ml/min/1.73 m(2). Subjects with eGFR ≥60 ml/min/1.73 m(2) (n = 20) were enrolled and their serum levels of FGF-23, intact PTH, and vitamin D metabolites were determined. Serum FGF-23 correlated inversely with 1,25(OH)2D (r = -0.717, p = 0.0004) and the 1,25(OH)2D/25-OH-D ratio (r = -0.518, p = 0.019), compared with a significant positive correlation between serum intact PTH and the 1,25(OH)2D/25-OH-D ratio (r = 0.562, p = 0.010). Multiple regression analyses revealed serum FGF-23 as a significant factor that was associated with serum 1,25(OH)2D (β = -0.593, p = 0.018), 1,25(OH)2D/25-OH-D ratio (β = -0.521, p = 0.025), and the 24,25(OH)2D/1,25(OH)2D ratio (β = 0.632, p = 0.008), and intact PTH as a significant factor associated with the 1,25(OH)2D/25-OH-D ratio (β = 0.445, p = 0.028). This study demonstrated that, even in subjects with eGFR ≥60 ml/min/1.73 m(2), FGF-23 might play an important role in the regulation of vitamin D metabolism. In addition to the established role of PTH, the association between FGF-23 and indices of vitamin D metabolism suggested the potential role of FGF-23 on phosphate metabolism in such patients. © 2015 S. Karger AG, Basel.

  10. Determination of eight nitrosamines in water at the ng L-1 levels by liquid chromatography coupled to atmospheric pressure chemical ionization tandem mass spectrometry

    International Nuclear Information System (INIS)

    Ripolles, Cristina; Pitarch, Elena; Sancho, Juan V.; Lopez, Francisco J.; Hernandez, Felix


    Highlights: · Eight N-nitrosamines in water by LC(APCI)MS/MS QqQ analysis. · Validation at two levels: 10 ng L -1 (LOQ) and 100 ng L -1 in drinking water. · Developed method applied to different types of water samples. · NDMA was the analyte more frequently detected and at the highest concentration levels. - Abstract: In this work, we have developed a sensitive method for detection and quantification of eight N-nitrosamines, N-nitrosodimethylamine (NDMA), N-nitrosomorpholine (NMor), N-nitrosomethylethylamine (NMEA), N-nitrosopirrolidine (NPyr), N-nitrosodiethylamine (NDEA), N-nitrosopiperidine (NPip), N-nitroso-n-dipropylamine (NDPA) and N-nitrosodi-n-butylamine (NDBA) in drinking water. The method is based on liquid chromatography coupled to tandem mass spectrometry, using atmospheric pressure chemical ionization (APCI) in positive mode with a triple quadrupole analyzer (QqQ). The simultaneous acquisition of two MS/MS transitions in selected reaction monitoring mode (SRM) for each compound, together with the evaluation of their relative intensity, allowed the simultaneous quantification and reliable identification in water at ppt levels. Empirical formula of the product ions selected was confirmed by UHPLC-(Q)TOF MS accurate mass measurements from reference standards. Prior to LC-MS/MS QqQ analysis, a preconcentration step by off-line SPE using coconut charcoal EPA 521 cartridges (by passing 500 mL of water sample) was necessary to improve the sensitivity and to meet regulation requirements. For accurate quantification, two isotope labelled nitrosamines (NDMA-d 6 and NDPA-d 14 ) were added as surrogate internal standards to the samples. The optimized method was validated at two concentration levels (10 and 100 ng L -1 ) in drinking water samples, obtaining satisfactory recoveries (between 90 and 120%) and precision (RSD -1 . The described methodology has been applied to different types of water samples: chlorinated from drinking water and wastewater treatment

  11. /sup 1/H NMR study of 2-deoxy-D-arabino-hexopyranose (2-deoxy-glucopyranose), 2-deoxy-D-lyxo-hexopyranose (2-deoxy-galactopyranose) and 2'-deoxy lactose. Shift increment studies in 2-deoxy carbohydrates

    Energy Technology Data Exchange (ETDEWEB)

    de Bruyn, A; Anteunis, M [Ghent Rijksuniversiteit (Belgium)


    Complete analyses are given of the /sup 1/H n.m.r. spectra at 300 MHz of D/sub 2/O solutions of 2-deoxy-D-arabino-hexopyranose, 2-deoxy-D-lyxo-hexopyranose and 2'-deoxy lactose. Chemical shifts in the deoxy monosaccharides and in 2'-deoxy lactose are compared with those previously obtained in the parent aldeohexopyranoses, glucobioses and D-galactopyranosol-D-glucoses. Increment values are suggested in order to predict chemical shifts in 2-deoxy derivatives from the well known rules for aldohexopyranoses.

  12. Free 25(OH)D concentrations are associated with atopy and lung function in children with asthma. (United States)

    Pollard, Suzanne L; Lima, John J; Mougey, Edward; Romero, Karina; Tarazona-Meza, Carla; Tomaino, Katherine; Guzmán, Gary Malpartida; Hansel, Nadia N; Checkley, William


    Evidence suggests free mono-hydroxyvitamin D (25[OH]D) concentrations are more strongly linked to certain outcomes than total concentrations; however, no studies have examined the relation between free 25(OH)D and respiratory or allergic disease. To examine associations between total and free 25(OH)D concentrations and asthma outcomes. We quantified total and free 25(OH)D concentrations in 137 Peruvian children with asthma and 152 children without asthma and examined associations with asthma outcomes. Mean age ± SD was 13 ± 2.5 years, and 50.2% were boys. Mean total and measured free 25(OH)D concentrations were 29 ± 9.5 ng/mL and 5.0 ± 1.3 pg/mL, respectively. Lower free but not total 25(OH)D concentrations were significantly associated with atopy in all children (total, odds ratio [OR] 1.3 per 10-ng/mL decrease, 95% confidence interval [CI] 0.95-1.7, P = .12; vs free, OR 1.3 per 1-pg/mL decrease, 95% CI 1.0-1.6, P = .02) and children with asthma (total, OR 1.1 per 10-ng/mL decrease, 95% CI 0.75-1.7, P = .57; vs free, OR 1.6 per 1-pg/mL decrease, 95% CI 1.0-2.5, P = .04). Free but not total 25(OH)D levels were significantly associated with pre-bronchodilator forced expiratory volume in 1 second (total, 0.11 L, -0.12 to 0.34, P = .34; vs free, 0.20 L, 0.021-0.39, P = .03) and forced vital capacity (total, 0.13 L, -0.12 to 0.37, P = .31; vs free, 0.22 L, 0.026-0.42, P = .03) Z-scores in children with asthma. Atopy, forced expiratory volume in 1 second, and forced vital capacity were more strongly linked to free than to total 25(OH)D concentrations, suggesting the free form might be more relevant in modulating allergic disease risk and pulmonary function in children with asthma. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  13. Efficiency of delivery observed treatment in hemodialysis patients: the example of the native vitamin D therapy. (United States)

    Delanaye, Pierre; Cavalier, Etienne; Fafin, Coraline; Dubois, Bernard E; Krzesinski, Jean-Marie; Moranne, Olivier


    Adherence to therapy is a relevant challenge in chronic hemodialysis patients. The directly observed therapy (DOT) could be an effective method to increase adherence for specific therapies. We aimed to study the performance of DOT versus home medication. We follow the impact of providing native vitamin D directly by the nurse after a dialysis session on the 25-hydroxyvitamin [25(OH)D] concentrations. In this observational study, we included 38 dialysis patients treated by stable dosage of cholecalciferol. DOT was implemented in December 2010. We considered the concentrations of 25-OH vitamin D three times before (T1 = June 2010, T2 = July 2010 and T3 = September 2010) and three times after the modification of prescription (T4 = February 2011, T5 = March 2011 and T6 = April 2011). Median age was 72 [62; 79] years and 48 % were diabetics. Mean body mass index was 26 ± 5 kg/m(2) and median dialysis vintage was 20 [8; 46] months. The patients were compared to themselves. Before DOT, median concentrations of 25(OH)D were 27 (14-36), 23 (17-31), 31 (22-38) ng/mL at T1, T2 and T3, respectively. When DOT was effective, the concentrations significantly increased to 34 (28-44), 35 (29-41), 39 (32-47) ng/mL at T4, T5 and T6, respectively. Before DOT, 19 patients (50 %) reached the target of 30 ng/mL. After DOT, 29 patients (76 %) reached the target concentration of 30 ng/mL. In hemodialysis patients, DOT is both simple and effective to increase the therapeutic impact to native vitamin D.

  14. Should vitamin D deficiency be corrected before parathyroidectomy? (United States)

    Randle, Reese W; Balentine, Courtney J; Wendt, Elizabeth; Schneider, David F; Chen, Herbert; Sippel, Rebecca S


    Vitamin D deficiency is common in patients with hyperparathyroidism, but the importance of replacement before surgery is controversial. We aimed to evaluate the impact of vitamin D deficiency on the extent of resection and risk of postoperative hypocalcemia for patients undergoing parathyroidectomy for primary hyperparathyroidism. We identified patients with primary hyperparathyroidism undergoing parathyroid surgery between 2000 and 2015 using a prospectively maintained database. Patients with normal (≥30 ng/mL) vitamin D were compared to those with levels less than 30 ng/mL. There were 1015 (54%) patients with normal vitamin D and 872 (46%) patients with vitamin D deficiency undergoing parathyroidectomy for primary hyperparathyroidism. Vitamin D deficiency was associated with higher preoperative parathyroid hormone (median 90 versus 77 pg/mL, P vitamin D. To achieve similar cure rates, patients with vitamin D deficiency were less likely to require removal of more than one gland (20% versus 30%, P vitamin D. Patients with vitamin D deficiency had similar rates of persistent (1.5% versus 2.0%, P = 0.43) and recurrent (1.7% versus 2.6%, P = 0.21) hyperparathyroidism. Postoperatively, both groups had equivalent rates of transient (2.3% versus 2.3%, P = 0.97) and permanent (0.2% versus 0.4%, P = 0.52) hypocalcemia. Restoring vitamin D in deficient patients should not delay the appropriate surgical treatment of primary hyperparathyroidism. Deficient patients are more likely to be cured with the excision of a single adenoma and no more likely to suffer persistence, recurrence, or hypocalcemia than patients with normal vitamin D. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. On QCD Q2-evolution of deuteron structure function F2D(xD, Q2) for xD>1

    International Nuclear Information System (INIS)

    Sidorov, A.V.; Tokarev, M.V.


    The deep-inelastic deuteron structure function (SF) F 2 D (x D ,Q 2 ) in the covariant approach in light-cone variables is considered. The x D and Q 2 -dependences of SF are calculated. The QCD analysis of generated data both for non-cumulative x D D >1 ranges was performed. It was shown that Q 2 -evolution of SF is valid for ranges 0.275 D D D -dependence of SF for the ranges is essentially different. 23 refs., 2 figs., 1 tab

  16. Rac2 controls tumor growth, metastasis and M1-M2 macrophage differentiation in vivo.

    Directory of Open Access Journals (Sweden)

    Shweta Joshi

    Full Text Available Although it is well-established that the macrophage M1 to M2 transition plays a role in tumor progression, the molecular basis for this process remains incompletely understood. Herein, we demonstrate that the small GTPase, Rac2 controls macrophage M1 to M2 differentiation and the metastatic phenotype in vivo. Using a genetic approach, combined with syngeneic and orthotopic tumor models we demonstrate that Rac2-/- mice display a marked defect in tumor growth, angiogenesis and metastasis. Microarray, RT-PCR and metabolomic analysis on bone marrow derived macrophages isolated from the Rac2-/- mice identify an important role for Rac2 in M2 macrophage differentiation. Furthermore, we define a novel molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin and MCSF receptor lead to the activation of Rac2 and potentially regulate macrophage M2 differentiation. Collectively, our findings demonstrate a macrophage autonomous process by which the Rac2 GTPase is activated downstream of the α4β1 integrin and the MCSF receptor to control tumor growth, metastasis and macrophage differentiation into the M2 phenotype. Finally, using gene expression and metabolomic data from our Rac2-/- model, and information related to M1-M2 macrophage differentiation curated from the literature we executed a systems biologic analysis of hierarchical protein-protein interaction networks in an effort to develop an iterative interactome map which will predict additional mechanisms by which Rac2 may coordinately control macrophage M1 to M2 differentiation and metastasis.

  17. Dicty_cDB: Contig-U13860-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available yp_01d11_M13Reverse Blue crab hypodermis, nor... 42 2e-04 2 ( ET898754 ) CHO_OF145xg03f1.ab1 CHO_OF Nicotian...NG DRAF... 38 7e-04 2 ( CV303138 ) CS_hyp_27d12_M13Reverse Blue crab hypodermis, nor... 42 0.001 2 ( CV46305...2 ) CS_hyp_52b08_M13Reverse Blue crab hypodermis, nor... 40 0.001 2 ( CU468915 ) Zebrafish DNA sequence from

  18. Field measurements of the atmospheric dry deposition fluxes and velocities of polycyclic aromatic hydrocarbons to the global oceans. (United States)

    González-Gaya, Belén; Zúñiga-Rival, Javier; Ojeda, María-José; Jiménez, Begoña; Dachs, Jordi


    The atmospheric dry deposition fluxes of 16 polycyclic aromatic hydrocarbons (PAHs) have been measured, for the first time, in the tropical and subtropical Atlantic, Pacific, and Indian Oceans. Depositional fluxes for fine (0.7-2.7 μm) and coarse (>2.7 μm) aerosol fractions were simultaneously determined with the suspended aerosol phase concentrations, allowing the determination of PAH deposition velocities (vD). PAH dry deposition fluxes (FDD) bound to coarse aerosols were higher than those of fine aerosols for 83% of the measurements. Average FDD for total (fine + coarse) Σ16PAHs (sum of 16 individual PAHs) ranged from 8.33 ng m(-2)d(-1) to 52.38 ng m(-2)d(-1). Mean FDD for coarse aerosol's individual PAHs ranged between 0.13 ng m(-2)d(-1) (Perylene) and 1.96 ng m(-2)d(-1) (Methyl Pyrene), and for the fine aerosol fraction these ranged between 0.06 ng m(-2)d(-1) (Dimethyl Pyrene) and 1.25 ng m(-2)d(-1) (Methyl Chrysene). The estimated deposition velocities went from the highest mean vD for Methyl Chrysene (0.17-13.30 cm s(-1)), followed by Dibenzo(ah)Anthracene (0.29-1.38 cm s(-1)), and other high MW PAHs to minimum values of vD for Dimethyl Pyrene (oceans.

  19. Monitoring of aflatoxin M1 in raw cow milk in Croatia during winter 2015

    Directory of Open Access Journals (Sweden)

    Nina Bilandžić


    Full Text Available A total of 548 raw milk samples were collected in the western, central and eastern regions of Croatia during February and March 2015. Aflatoxin M1 (AFM1 concentrations were quantified by the enzyme immunoassay method. The method limits of detection (LOD and quantification (LOQ were 22.2 and 34.2 ng/kg, respectively. The mean AFM1 levels measured in the three regions were (ng/kg as follows: western 3.69, central 3.11 and eastern 4.14. In total, the 548 samples analysed concentrations were below the LOD value and accordingly below the European Union maximum residue level (EU MRL of 50 ng/kg. The results suggest an absence of use of contaminated with aflatoxin B1 supplementary feedstuff for lactating cows in winter 2015. Such results might be related to the improved storage conditions for feed as well as to the enhanced and more stringent feed control system for mycotoxins in Croatia.

  20. Identity of M2A (D2-40) antigen and gp36 (Aggrus, T1A-2, podoplanin) in human developing testis, testicular carcinoma in situ and germ-cell tumours

    DEFF Research Database (Denmark)

    Sonne, Si Brask; Herlihy, Amy S; Hoei-Hansen, Christina E


    Testicular germ-cell tumours of young adults are derived from a pre-invasive intratubular lesion, carcinoma in situ (CIS). In a recent genome-wide gene expression screening using cDNA microarrays, we found PDPN over-expressed in CIS compared to normal adult testis. PDPN encodes podoplanin (Aggrus...... gonocytes and immature Sertoli cells, similar to the expression pattern of M2A antigen, a previously identified marker for CIS and seminoma. This reinforced our previous proposal that M2A (D2-40) antigen was identical to gp36 (podoplanin, Aggrus, T1A-2). Our findings also suggest that podoplanin has...

  1. Ceramics and M.H.D

    International Nuclear Information System (INIS)

    Yvars, M.


    The materials considered for the insulating walls of a M.H.D. converter are Al 2 O 3 , and the calcium or strontium zirconates. For the conducting walls electricity conducting oxides are being considered such as ZrO 2 or CrO 3 La essentially. The principle of M.H.D. systems is recalled, the materials considered are described as is their behaviour in the corrosive atmospheres of M.H.D. streams [fr

  2. Theoretical descriptions of novel triplet germylenes M1-Ge-M2-M3 (M1 = H, Li, Na, K; M2 = Be, Mg, Ca; M3 = H, F, Cl, Br). (United States)

    Kassaee, Mohamad Zaman; Ashenagar, Samaneh


    In a quest to identify new ground-state triplet germylenes, the stabilities (singlet-triplet energy differences, ΔE S-T ) of 96 singlet (s) and triplet (t) M 1 -Ge-M 2 -M 3 species were compared and contrasted at the B3LYP/6-311++G**, QCISD(T)/6-311++G**, and CCSD(T)/6-311++G** levels of theory (M 1  = H, Li, Na, K; M 2  = Be, Mg, Ca; M 3  = H, F, Cl, Br). Interestingly, F-substituent triplet germylenes (M 3  = F) appear to be more stable and linear than the corresponding Cl- or Br-substituent triplet germylenes (M 3  = Cl or Br). Triplets with M 1  = K (i.e., the K-Ge-M 2 -M 3 series) seem to be more stable than the corresponding triplets with M 1  = H, Li, or Na. This can be attributed to the higher electropositivity of potassium. Triplet species with M 3  = Cl behave similarly to those with M 3  = Br. Conversely, triplets with M 3  = H show similar stabilities and linearities to those with M 3  = F. Singlet species of formulae K-Ge-Ca-Cl and K-Ge-Ca-Br form unexpected cyclic structures. Finally, the triplet germylenes M 1 -Ge-M 2 -M 3 become more stable as the electropositivities of the α-substituents (M 1 and M 2 ) and the electronegativity of the β-substituent (M 3 ) increase.

  3. Insuficiência e deficiência de vitamina D em pacientes portadores de doença renal crônica

    Directory of Open Access Journals (Sweden)

    Herculano Ferreira Diniz


    Full Text Available INTRODUÇÃO: Hipovitaminose D é bem documentada em pacientes portadores de doença renal crônica (DRC. Espera-se níveis inferiores em habitantes de regiões não tropicais em relação aos habitantes de regiões tropicais, pela inferição de uma maior exposição solar e maior produção de vitamina D. OBJETIVO: Analisar os níveis séricos de vitamina D, como 25-hidroxivitamina D - 25(OHD, de 125 pacientes brasileiros portadores de DRC em fase pré-dialítica. MÉTODOS: Foram estudados 125 pacientes (57,4 ± 16,2 anos, 78 brancos e 55,2% homens, com creatinina de 2,67 ± 1,73 mg/dL e o clearance estimado 43,7 ± 34,5 mL/min. O índice de massa corporal era de 27,4 ± 4,7 kg/m² e a circunferência abdominal de 95,0 ± 14,0 cm. O cálcio era de 9,3 ± 0,6 mg/dL, o paratormônio intacto (PTHi 212,6 ± 221,2 pg/mL e a albumina sérica 4,2 ± 0,6 g/dL. A média de 25(OHD era de 23,9 ± 10,7 ng/mL. RESULTADOS: Dos 125 pacientes, 92 (72,6% apresentavam níveis de 25(OHD < 30 ng/mL, sendo que 65 (52% apresentavam insuficiência (15-29 ng/mL; 27 (21,5% apresentavam deficiência (5-14 ng/mL e apenas um paciente apresentava deficiência severa < 5 ng/mL. Não foram observadas diferenças entre os níveis de 25(OHD nos pacientes estratificados quanto ao estágio de DRC. Os níveis de 25(OHD foram maiores nos homens (38,1 ± 20,6 versus 22,4 ± 9,7 ng/ml; p < 0,0001, havendo também uma correlação inversa entre os níveis de 25(OHD e de PTHi, proteinúria e circunferência abdominal, e uma correlação positiva entre 25(OHD e cálcio total e albumina sérica. Na análise multivariada, encontrou-se apenas correlação inversa entre 25(OHD e circunferência abdominal e PTHi. CONCLUSÃO: A despeito de a população do Brasil estar em um clima tropical, a maioria dos pacientes analisados apresentou níveis séricos subótimos de vitamina D, podendo este achado estar relacionado ao desenvolvimento de hiperparatireoidismo.

  4. Severe vitamin D deficiency in Arab-American women living in Dearborn, Michigan. (United States)

    Hobbs, Raymond D; Habib, Zeina; Alromaihi, Dalal; Idi, Leila; Parikh, Nayana; Blocki, Frank; Rao, D Sudhaker


    To determine the prevalence and degree of 25-hydroxyvitamin D deficiency in a group of Arab-American women in the largest, most-concentrated Arab-American settlement in the United States and to search for correlations with dress, diet, and use of vitamin D-fortified foods and vitamin supplements. In this cross-sectional study, Arab-American women, 18 years and older, who attended an ethnic market on April 7 or 14, 2007, were recruited. Participants were interviewed by bilingual English- and Arabic-speaking investigators using a semi-structured interview to assess dress; demographic variables; medical history; medication use; clinical symptoms associated with vitamin D deficiency (eg, joint or bone pain, muscle weakness); and dietary intake of vitamin D from fortified orange juice, milk, and vitamin supplementation. Blood samples were drawn to measure concentrations of serum calcium, creatinine, phosphorus, alkaline phosphatase, parathyroid hormone, and 25-hydroxyvitamin D. Participants were initially divided into 2 groups based on whether the woman was veiled and further subdivided into 3 groups on the basis of vitamin D intake from supplemented food sources (milk or vitamin D-fortified orange juice) and vitamin pills: unveiled, veiled and taking supplements, and veiled and taking no supplements. Eighty-seven women participated. Serum 25-hydroxyvitamin D levels were uniformly low, with the highest levels in the unveiled group (median [interquartile range]) (8.5 ng/mL [5.75-13.5 ng/mL]) followed by the veiled, supplemented group (7 ng/mL [4-11.5 ng/mL]) and the veiled, unsupplemented group (4 ng/mL [2-6.8 ng/mL]). 25-Hydroxyvitamin D levels were lower in women with less experience in the United States and in those with less education. Vitamin D-fortified orange juice consumption had a greater positive predictive effect on serum 25-hydroxyvitamin D levels than either milk or vitamin pills and may possibly serve as a surrogate marker for vitamin D awareness. Vitamin D

  5. Stimuli that induce a cholinergic neuronal phenotype of NG108-15 cells upregulate ChAT and VAChT mRNAs but fail to increase VAChT protein

    Czech Academy of Sciences Publication Activity Database

    Doležal, Vladimír; Castell, X.; Tomasi, M.; Diebler, M. F.


    Roč. 54, č. 4 (2001), s. 363-373 ISSN 0361-9230 R&D Projects: GA ČR GA305/98/0469 Institutional research plan: CEZ:AV0Z5011922 Keywords : choline acetyltransferase * vesicular acetylcholine transporter * NG108-15 Subject RIV: FH - Neurology Impact factor: 1.783, year: 2001

  6. Flood hazard assessment using 1D and 2D approaches (United States)

    Petaccia, Gabriella; Costabile, Pierfranco; Macchione, Francesco; Natale, Luigi


    The EU flood risk Directive (Directive 2007/60/EC) prescribes risk assessment and mapping to develop flood risk management plans. Flood hazard mapping may be carried out with mathematical models able to determine flood-prone areas once realistic conditions (in terms of discharge or water levels) are imposed at the boundaries of the case study. The deterministic models are mainly based on shallow water equations expressed in their 1D or 2D formulation. The 1D approach is widely used, especially in technical studies, due to its relative simplicity, its computational efficiency and also because it requires topographical data not as expensive as the ones needed by 2D models. Even if in a great number of practical situations, such as modeling in-channel flows and not too wide floodplains, the 1D approach may provide results close to the prediction of a more sophisticated 2D model, it must be pointed out that the correct use of a 1D model in practical situations is more complex than it may seem. The main issues to be correctly modeled in a 1D approach are the definition of hydraulic structures such as bridges and buildings interacting with the flow and the treatment of the tributaries. Clearly all these aspects have to be taken into account also in the 2D modeling, but with fewer difficulties. The purpose of this paper is to show how the above cited issues can be described using a 1D or 2D unsteady flow modeling. In particular the Authors will show the devices that have to be implemented in 1D modeling to get reliable predictions of water levels and discharges comparable to the ones obtained using a 2D model. Attention will be focused on an actual river (Crati river) located in the South of Italy. This case study is quite complicated since it deals with the simulation of channeled flows, overbank flows, interactions with buildings, bridges and tributaries. Accurate techniques, intentionally developed by the Authors to take into account all these peculiarities in 1D and 2

  7. Pentacyclic ingamine-type alkaloids, a new antiplasmodial pharmacophore from the marine sponge petrosid Ng5 Sp5 (United States)

    Two new pentacyclic ingamine- type alkaloids, namely 22(S)-hydroxyingamine A (2) and dihydroingenamine D (3), together with the known ingamine A (1) have been isolated from marine sponge Petrosid Ng5 Sp5 (Family: Petrosiidae) obtained from the open repository of National Cancer Institute, USA. The s...

  8. Elevation in D-dimer concentrations is positively correlated with gestation in normal uncomplicated pregnancy

    Directory of Open Access Journals (Sweden)

    Jeremiah ZA


    Full Text Available Zaccheaus A Jeremiah,1 Teddy C Adias,2 Margaret Opiah,3 Siyeoforiye P George,4 Osaro Mgbere,5 Ekere J Essien61Department of Medical Laboratory Sciences, Niger Delta University, Wilberforce Island, Nigeria; 2Bayelsa State College of Health Technology, Ogbia-Town, Nigeria; 3Department of Maternal and Child Health, Faculty of Nursing, Niger Delta University, Wilberforce Island, Nigeria; 4Postgraduate Hematology Unit, Rivers State University of Science and Technology, Port Harcourt, Nigeria; 5Houston Department of Health and Human Services, Houston, TX, USA; 6Institute of Community Health, University of Houston, Houston, TX, USABackground: D-dimer levels have been reported to increase progressively during pregnancy, but how this affects Nigerian women is not well known.Objective: This study aims to determine the D-dimer concentration and its relationship to other coagulation parameters among pregnant women in Port Harcourt, Nigeria.Method: In a cross-sectional observational study conducted in Port Harcourt, Nigeria, 120 pregnant women and 60 nonpregnant controls, drawn from a tertiary health institution in the Niger Delta, Nigeria, were assessed, using the standard procedures, for the following parameters: D-dimer concentration, prothrombin time, activated partial thromboplastin time, platelet count, hemoglobin, and packed cell volume.Results: The median D-dimer concentration of 153.1 ng/mL in the pregnant group was found to be significantly elevated when compared with the control value of 118.5 ng/mL (t = 2.348, P = 0.021. Conversely, there was a marked depression in the platelet count among pregnant women (193.5 × 109/L when compared with 229.0 × 109/L in the control group (t = 3.424; P = 0.001. There was no statistically significant difference in the values for the prothrombin time and the activated partial thromboplastin time between pregnant and nonpregnant women. D-dimer values correlated positively and significantly with gestation (r = 0

  9. Correlation of Serum Androgens and Pituitary Hormone Levels with Serum PSA Less Than 2.5 NG/ML

    Directory of Open Access Journals (Sweden)

    Mustafa Sofikerim


    Full Text Available The aim of this clinical study was to determine whether there is a relationship between total serum testosterone, free testosterone, FSH (Follicle-Stimulating Hormone, LH (Luteinizing Hormone and serum prostate specific antigen (PSA levels. We postulated that such a correlation existed then the use of hormone specific reference ranges might enhance the usefullness of PSA concentrations <2.5 ng/mL as a marker for prostate cancer.

  10. The structural, electronic, magnetic, and mechanical properties of perovskite oxides PbM1/2Nb1/2O3 (M = Fe, Co and Ni) (United States)

    Erkisi, A.; Surucu, G.; Deligoz, E.


    In this study, the structural, electronic, magnetic, and mechanical properties of perovskite oxides PbM1/2Nb1/2O3 (M = Fe, Co and Ni) are investigated. The systems are treated in ferromagnetic order. The calculations are carried out in the framework of density functional theory (DFT) within the plane-wave pseudopotential method. The exchange-correlation potential is approximated by generalized-gradient spin approach (GGA). The intra-atomic Coulomb repulsion is also taken into account in calculations (GGA + U). We have considered two generalized-gradient spin approximation functionals, which are Perdew-Burke-Ernzerhof (PBE) and PBE for solids (PBEsol) for structural parameter calculations when it included Hubbard potential. Although the spin-polarized electronic band structures of PbCo1/2Nb1/2O3 and PbNi1/2Nb1/2O3 systems exhibit metallic property in ferromagnetic phase, a bandgap is observed in spin-down states of PbFe1/2Nb1/2O3 resulting in half-metallic behavior. The main reason for this behavior is attributed to the hybridization between d-states of transition metal atoms and p-states of oxygen atoms. The stability mechanically and the calculated mechanical properties by using elastic constants show that these compounds are mechanically stable in tetragonal phase and have anisotropic character mechanically.

  11. Photonic integrated transmitter and receiver for NG-PON2 (United States)

    Tavares, Ana; Lopes, Ana; Rodrigues, Cláudio; Mãocheia, Paulo; Mendes, Tiago; Brandão, Simão.; Rodrigues, Francisco; Ferreira, Ricardo; Teixeira, António


    In this paper the authors present a monolithic Photonic Integrated Circuit which includes a transmitter and a receiver for NG-PON2. With this layout it is possible to build an OLT and, by redesigning some filters, also an ONU. This technology allows reducing the losses in the transmitter and in the receiver, increasing power budget, and also reducing the OEO conversions, which has been a major problem that operators want to surpass.

  12. Fen Eğitiminde Öğrenme Döngüsü Modelleri

    Directory of Open Access Journals (Sweden)

    Yüksel Keleş


    Full Text Available Öğrenme döngüleri yapılandırıcı yaklaşımla fen eğitimi için geliştirilmiş modellerdir. Öğrenme döngüsü modelleri birbirini izleyen 3, 5 veya 7 evreden oluşmaktadır, bu evreler birbirinden ayrı ya da doğrusal değildir. Öğrenme döngüsü uygulamalarının yaratıcı ve eleştirel düşünme için öğrencileri teşvik etmesi ve bilime karşı olumlu tutum geliştirilmesi beklenmektedir. Kavramların daha iyi anlaşılmasına ve öğrencilerde ileri düşünme yeteneklerinin gelişmesine yardımcı olacağı düşünülmektedir. Bu makalede 5E ve 7E modellerinin her bir evresindeki öğrenci ve öğretmen rolleri üzerinde durulmaktadır. Model üzerinde gerçekleştirilen çalışmaların sonuçlarına dayanılarak modelin sağlayacağı olası faydalar tartışılmaktadır. Fen eğitiminde öğrenme döngüsü uygulamalarının yaygınlaştırılması amacıyla, öğretmen yetiştirme süreçlerinde öğrenme döngüsü modellerine yer verilmesi önerilmektedir.

  13. Optimization of a two-dimensional liquid chromatography-supercritical fluid chromatography-mass spectrometry (2D-LC-SFS-MS) system to assess "in-vivo" inter-conversion of chiral drug molecules. (United States)

    Goel, Meenakshi; Larson, Eli; Venkatramani, C J; Al-Sayah, Mohammad A


    Enantioselective analysis is an essential requirement during the pharmaceutical development of chiral drug molecules. In pre-clinical and clinical studies, the Food and Drug Administration (FDA) mandates the assessment of "in vivo" inter-conversion of chiral drugs to determine their physiological effects. In-vivo analysis of the active pharmaceutical ingredient (API) and its potential metabolites could be quite challenging due to their low abundance (ng/mL levels) and matrix interferences. Therefore, highly selective and sensitive analytical techniques are required to separate the API and its metabolites from the matrix components and one another. Additionally, for chiral APIs, further analytical separation is required to resolve the API and its potential metabolites from their corresponding enantiomers. In this work, we demonstrate the optimization of our previously designed two-dimensional liquid chromatography-supercritical fluid chromatography-mass spectrometry (2D-LC-SFC -MS) system to achieve 10 ng/mL detection limit [1]. The first LC dimension, used as a desalting step, could efficiently separate the API from its potential metabolites and matrix components. The API and its metabolites were then trapped/focused on small trapping columns and transferred onto the second SFC dimension for chiral separation. Detection can be achieved by ultra-violet (UV) or MS detection. Different system parameters such as column dimensions, transfer volumes, trapping column stationary phase, system tubing internal diameter (i.d.), and detection techniques, were optimized to enhance the sensitivity of the 2D-LC-SFC-MS system. The limit of detection was determined to be 10 ng/mL. An application is described where a mouse hepatocyte treated sample was analyzed using the optimized 2D-LC-SFC-MS system with successful assessment of the ratio of API to its metabolite (1D-LC), as well as the corresponding enantiomeric excess values (% e.e.) of each (2D-SFC). Copyright © 2018

  14. Regulation of mouse hepatic CYP2D9 mRNA expression by growth and adrenal hormones. (United States)

    Jarukamjorn, Kanokwan; Sakuma, Tsutomu; Jaruchotikamol, Atika; Oguro, Miki; Nemoto, Nobuo


    The constitutive expression of CYP2D9 is sexually dimorphic, namely, strong in males, but diminutive in females. Repetition of mimic growth hormone (GH) secretion pattern impressively returned the mRNA expression level to that in intact mice: the GH secretion pattern's regulation of CYP2D9 mRNA expression has been predominantly disrupted by exogenous GH-administration. The extensive decline of CYP2D9 mRNA expression becoming a sexually non-specific P450 in 9-week-old male mice exposed as neonates to monosodium L-glutamate (MSG) suggested that the male GH secretion pattern is a key to the regulation of male-specific CYP2D9 mRNA expression in adult mice. Dexamethasone (Dex) showed possibility to induce CYP2D9 mRNA expression in adult MSG-neonatally treated mice of either sex. However, the antagonism was observed by co-administration of Dex and GH in the males. Dex-administration in adrenalectomized mice significantly elevated CYP2D9 mRNA expression levels. These findings suggest that an adrenal hormone participates in the regulatory mechanism of CYP2D9 mRNA expression in association with GH.

  15. Aflatoxin M1 levels in raw milk, pasteurised milk and infant formula

    Directory of Open Access Journals (Sweden)

    Sharaf S. Omar


    Full Text Available The incidence of contamination of aflatoxin M1 (AFM1 in milk samples collected from the Jordanian market was investigated by using the competitive enzyme linked immunosorbent assay (ELISA technique. A total of 175 samples were collected during 2014-2015. All tested samples were contaminated with various levels of AFM1 ranging from 9.71 to 288.68 ng/kg. The concentration of AFM1 in 66% of fresh milk samples was higher than the maximum tolerance limit accepted by the European Union (50 ng/kg and 23% higher than the maximum tolerance limit accepted by the US (500 ng/kg. Percentages of contaminated raw cow, sheep, goat and camel milk exceeding the European tolerance limit were 60, 85, 75 and 0%, respectively. Of AFM1 contaminated pasteurised cow milk samples, 12% exceeded the European tolerance limit with a range of contamination between 14.60 and 216.78 ng/kg. For infant formula samples, the average concentration of AFM1 was 120.26 ng/kg (range from 16.55 to 288.68 ng/kg, the concentration of AFM1 in 85% of infant formula samples was higher than the maximum tolerance limit accepted by the European Union and the US (25 ng/kg.

  16. Diversification of the vacAs1m1 and vacAs2m2 strains of Helicobacter pylori in Meriones unguiculatus

    Directory of Open Access Journals (Sweden)

    Sandra Mendoza Elizalde


    Full Text Available The bacterium Helicobacter pylori exhibits great genetic diversity, and the pathogenic roles of its virulence factors have been widely studied. However, the evolutionary dynamics of H. pylori strains during stomach colonization are not well characterized. Here, we analyzed the microevolutionary dynamics of the toxigenic strain vacAs1m1, the non-toxigenic strain vacAs2m2, and a combination of both strains in an animal model over time. Meriones unguiculatus were inoculated with the following bacteria: group 1–toxigenic strain vacAs1m1/cagA+/cagE+/babA2+; ST181, group 2–non-toxigenic strain vacAs2m2/ cagA+/ cagE+/ babA2+; ST2901, and group 3–both strains. The gerbils were euthanized at different time points (3, 6, 12 and 18 months. In group 1, genetic alterations were observed at 6 and 12 months. With the combination of both strains, group 3 also exhibited genetic alterations at 3 and 18 months; moreover, a chimera, vacA m1-m2, was detected. Additionally, four new sequence types (STs were reported in the PubMLST database for H. pylori. Synonymous and non-synonymous mutations were analyzed and associated with alterations in amino acids. Microevolutionary analysis of the STs (PHYLOViZ identified in each group revealed many mutational changes in the toxigenic (vacAs1m1 and non-toxigenic (vacAs2m2 strains. Phylogenetic assessments (eBURST did not reveal clonal complexes. Our findings indicate that the toxigenic strain, vacAs1m1, and a combination of toxigenic and non-toxigenic strains acquired genetic material by recombination. The allelic combination, vacAs2m1, displayed the best adaptation in the animal model over time, and a chimera, m1-m2, was also identified, which confirmed previous reports.

  17. Calciotrophic hormones and hyperglycemia modulate vitamin D receptor and 25 hydroxyy vitamin D 1-α hydroxylase mRNA expression in human vascular smooth muscle cells. (United States)

    Somjen, D; Knoll, E; Sharon, O; Many, A; Stern, N


    Estrogen receptors (ERα and ERβ), the vitamin D receptor (VDR) and 25 hydroxyy vitamin D 1-α hydroxylase (1OHase) mRNA are expressed in vascular smooth muscle cells (VSMC). In these cells estrogenic hormones modulate cell proliferation as measured by DNA synthesis (DNA). In the present study we determined whether or not the calciotrophic hormones PTH 1-34 (PTH) and less- calcemic vitamin D analog QW as well as hyperglycemia can regulate DNA synthesis and CK. E2 had a bimodal effect on VSMC DNA synthesis, such that proliferation was inhibited at 30nM but stimulated at 0.3nM. PTH at 50nM increased, whereas QW at 10nM inhibited DNA synthesis. Hyperglycemia inhibited the effects on high E2, QW and PTH on DNA only. Both QW and PTH increased ERα mRNA expression, but only PTH increased ERβ expression. Likewise, both PTH and QW stimulated VDR and 1OHase expression and activity. ERβ, VDR and 1OHase expression and activity were inhibited by hyperglycemia, but ERα expression was unaffected by hyperglycemia. In conclusion, calcitrophic hormones modify VSMC growth and concomitantly affect ER expression in these cells as well as the endogenous VSMC vitamin D system elements, including VDR and 1OHase. Some of the later changes may likely participate in growth effects. Of importance in the observation is that several regulatory effects are deranged in the presence of hyperglycemia, particularly the PTH- and vitamin D-dependent up regulation of VDR and 1OHase in these cells. The implications of these effects require further studies. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Total scattering cross-sections for the systems nH2 + nH2, pH2 + pH2, nD2 + nD2, oD2 + oD2 and HD + HD for relative energies below ten milli-electron volts

    International Nuclear Information System (INIS)

    Johnson, D.L.


    Relative total scattering cross sections for nH 2 + nH 2 , pH 2 + pH 2 , nD 2 + nD 2 , oD 2 + oD 2 , and HD + HD were measured with inclined nozzle beams derived from nozzle sources and intersecting at 21 0 . Both nozzles could be varied in temperature from 4.2K to 300K to provide the velocity range for the cross sections. The use of a parahydrogen converter allowed the measurement of the pH 2 + pH 2 and oD 2 + oD 2 cross sections. Cross sections for the H 2 + H 2 were measured over a relative velocity range of 200 m/s to 1450 m/s. The nH 2 + nH 2 results show an undulation in the velocity range between 350 m/s and 400 m/s that corresponds to a l = 3 orbiting resonance. Analysis of the pH 2 + pH 2 cross section indicates a l = 4 orbiting resonance near 586 m/s. This resonance has a peak energy of 1.79 meV and a measured energy width of 1.05 meV, both which agree well with theoretical predictions. The D 2 + D 2 cross sections have been measured in the velocity range between 190 m/s and 1000 m/s. No orbiting resonances have been observed, but in the oD 2 + oD 2 cross section a deep minimum between the l = 4 and the l = 5 resonances at low velocities is clearly suggested. Initial measurements of the HD + HD cross section suggests the presence of the l = 4 orbiting resonance near a relative velocity of 300 m/s. The experimental results for each system were normalized to the total cross sections, which were convoluted to account for experimental velocity and angular dispersions. Three different potentials were considered, but a chi-square fit of the data indicates that the Schaefer and Meyer potential, which has been theoretically obtained from first principles, provides the best overall description of the hydrogen systems in the low collisional energy range

  19. Immunoassays for riboflavin and flavin mononucleotide using antibodies specific to d-ribitol and d-ribitol-5-phosphate. (United States)

    Ravi, G; Venkatesh, Yeldur P


    Riboflavin (vitamin B 2 ), a water-soluble vitamin, plays a key role in maintaining human health. Though, numerous methods have been reported for the determination of total riboflavin (TRF) content in foods and biological samples, very few methods are reported for quantifying riboflavin and its coenzymes [flavin mononucleotide (FMN); flavin adenine dinucleotide (FAD)] individually. Recently, we have demonstrated that antibodies specific to d-ribitol and d-ribitol-5-phosphate also recognize riboflavin and FMN, respectively, and not vice-versa. In this study, we have evaluated these two antibodies for the analysis of riboflavin and FMN by indirect competitive ELISA (icELISA) in selected foods and pharmaceuticals. Under the optimal assay conditions, 50% inhibition concentration (IC 50 ) and limit of detection (LOD, IC 10 ) were 3.41ng/mL and 0.02ng/mL for riboflavin, and 7.84ng/mL and 0.24ng/mL for FMN, respectively, with detectable concentration range between 0.1 and 100ng of analytes and riboflavin and FMN) from the same food samples showed variation in their values compared to TRF, and were in good agreement with values obtained from HPLC and AOAC methods. Further, spiking and recovery analysis of food samples and pharmaceuticals showed no significant matrix effects. The immunoassays were validated in terms of accuracy and precision using inter- and intra-assays. The immunoassays developed in this study are sensitive and appears feasible for screening a large number of samples in the quantification of riboflavin and FMN in various biological samples, pharmaceuticals and natural/processed foods. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Expression of NgBR Is Highly Associated with Estrogen Receptor Alpha and Survivin in Breast Cancer (United States)

    North, Paula; Kong, Amanda; Huang, Jian; Miao, Qing Robert


    NgBR is a type I receptor with a single transmembrane domain and was identified as a specific receptor for Nogo-B. Our recent findings demonstrated that NgBR binds farnesylated Ras and recruits Ras to the plasma membrane, which is a critical step required for the activation of Ras signaling in human breast cancer cells and tumorigenesis. Here, we first use immunohistochemistry and real-time PCR approaches to examine the expression patterns of Nogo-B and NgBR in both normal and breast tumor tissues. Then, we examine the relationship between NgBR expression and molecular subtypes of breast cancer, and the roles of NgBR in estrogen-dependent survivin signaling pathway. Results showed that NgBR and Nogo-B protein were detected in both normal and breast tumor tissues. However, the expression of Nogo-B and NgBR in breast tumor tissue was much stronger than in normal breast tissue. The statistical analysis demonstrated that NgBR is highly associated with ER-positive/HER2-negative breast cancer. We also found that the expression of NgBR has a strong correlation with the expression of survivin, which is a well-known apoptosis inhibitor. The correlation between NgBR and survivin gene expression was further confirmed by real-time PCR. In vitro results also demonstrated that estradiol induces the expression of survivin in ER-positive T47D breast tumor cells but not in ER-negative MDA-MB-468 breast tumor cells. NgBR knockdown with siRNA abolishes estradiol-induced survivin expression in ER-positive T47D cells but not in ER-negative MDA-MB-468 cells. In addition, estradiol increases the expression of survivin and cell growth in ER-positive MCF-7 and T47D cells whereas knockdown of NgBR with siRNA reduces estradiol-induced survivin expression and cell growth. In summary, these results indicate that NgBR is a new molecular marker for breast cancer. The data suggest that the expression of NgBR may be essential in promoting ER-positive tumor cell proliferation via survivin induction

  1. Evaluation of PCA3 and multiparametric MRI’s: collective benefits before deciding initial prostate biopsy for patients with PSA level between 3-10ng/mL

    Directory of Open Access Journals (Sweden)

    Sezgin Okcelik


    Full Text Available ABSTRACT Objective To analyze the contribution of multiparametric MRI and PCA3 assay, pre- decision of initial biopsy in PSA level between 3-10 ng/mL patients with normal digital rectal examination(DRE. Materials and Methods PSA level 3-10 ng/mL ,patients, with normal DRE results and no previous prostate biopsy history, were included in this study. Each patient underwent multiparametric MRI one week before biopsy. Urine sample taking for PCA3 examination preceded the biopsy. Systematic and targeted biopsies were conducted. Patients with high PSA levels were seperated into two groups as: high PCA3 scored and low PCA3 scored. Then each group was divided into two sub-groups as: MRI lesion positive and negative. Tumor incidence, positive predictive values(PPV and negative predictive values(NPV were calculated. Results 53 patients were included between February 2013 and March 2014.Mean age 61.22 ± 1.06. Mean PSA value 5.13 ± 0.19 ng / mL. Mean PCA3 score 98.01 ± 23.13 and mean prostate size was 48.96 ± 2.67 grams. Fourty nine patients had both PCA3 score and multiparametric MRI. The PCA3’s PPV value was 58.33%. If multiparametric MRI lesions are added to high PCA3 scores , the PPV appears to elevate to 91.66%. NPV of PCA3 was 96%. NPV was 95% when there was no lesion in the multiparametric MRI with low PCA3 scores. Sensitivity was 91.66% , specificity was 95% respectively. Conclusion Adding multimetric MRI can also support biopsy decision for patients with high PCA3 value. When PCA3 value is low, patients can be survailled without any need to take a MRI.

  2. Rac1 Regulates the Activity of mTORC1 and mTORC2 and Controls Cellular Size (United States)

    Saci, Abdelhafid; Cantley, Lewis C.; Carpenter, Christopher L.


    SUMMARY Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that exists in two separate complexes, mTORC1 and mTORC2, that function to control cell size and growth in response to growth factors, nutrients, and cellular energy levels. Low molecular weight GTP-binding proteins of the Rheb and Rag families are key regulators of the mTORC1 complex, but regulation of mTORC2 is poorly understood. Here, we report that Rac1, a member of the Rho family of GTPases, is a critical regulator of both mTORC1 and mTORC2 in response to growth-factor stimulation. Deletion of Rac1 in primary cells using an inducible-Cre/Lox approach inhibits basal and growth-factor activation of both mTORC1 and mTORC2. Rac1 appears to bind directly to mTOR and to mediate mTORC1 and mTORC2 localization at specific membranes. Binding of Rac1 to mTOR does not depend on the GTP-bound state of Rac1, but on the integrity of its C-terminal domain. This function of Rac1 provides a means to regulate mTORC1 and mTORC2 simultaneously. PMID:21474067

  3. Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development. (United States)

    Morales, Eva; Guxens, Mònica; Llop, Sabrina; Rodríguez-Bernal, Clara L; Tardón, Adonina; Riaño, Isolina; Ibarluzea, Jesús; Lertxundi, Nerea; Espada, Mercedes; Rodriguez, Agueda; Sunyer, Jordi


    To investigate whether circulating 25-hydroxyvitamin D(3) [25(OH)D(3)] concentration in pregnancy is associated with neuropsychological development in infants. The Spanish population-based cohort study INfancia y Medio Ambiente Project recruited pregnant women during the first trimester of pregnancy between November 2003 and February 2008. Completed data on 1820 mother-infant pairs were used. Maternal plasma 25(OH)D(3) concentration was measured by high-performance liquid chromatography in pregnancy (mean 13.5 ± 2.1 weeks of gestation). Offspring mental and psychomotor scores were assessed by trained psychologists at age 14 months (range, 11-23) by using the Bayley Scales of Infant Development. β-Coefficients with 95% confidence intervals (CIs) of mental and psychomotor scores associated with continuous or categorical concentrations of maternal plasma 25(OH)D(3) were calculated by using linear regression analysis. The median plasma value of 25(OH)D(3) in pregnancy was 29.6 ng/mL (interquartile range, 21.8-37.3). A positive linear relationship was found between circulating concentrations of maternal 25(OH)D(3) concentrations in pregnancy and mental and psychomotor scores in the offspring. After adjustment for potential confounders, infants of mothers with 25(OH)D(3) concentrations in pregnancy >30 ng/mL showed higher mental score (β = 2.60; 95% CI 0.63-4.56) and higher psychomotor score (β = 2.32; 95% CI 0.36-4.28) in comparison with those of mothers with 25(OH)D(3) concentrations <20 ng/mL. Higher circulating concentration of maternal 25(OH)D(3) in pregnancy was associated with improved mental and psychomotor development in infants.

  4. Radioimmunoassays for lg classes G, A, M, D, and E in spinal fluids: normal values of different age groups

    International Nuclear Information System (INIS)

    Nerenberg, S.T.; Prasad, R.


    Radioimmunoassay procedures of sufficient sensitivity (lgG, 0.5 μg per 100 μl; lgA, 25.0 ng. per 100 μl; lgM, 10.0 ng. per 100 μl; lgD, 0.5 U.* per 100 μl; and lgE, 1.0 U.* per 100 μl) were developed to detect and quantitate all 5 immunoglobulin classes in the cerebrospinal fluid on small aliquots (1 ml.) of unconcentrated cerebrospinal fluid. All 5 immunoglobulin classes were routinely detected in normal individuals for the first time, the levels varying with different age groups for lgG and A but not for the remaining immunoglobulin classes. Race and sex had no effect. Standardization of techniques and establishment of normal values for different age groups sets the stage for determination of immunoglobulin changes related to central nervous system disease

  5. Kruuda kurb mäng

    Index Scriptorium Estoniae


    Oliver Kruuda müüs oma võlakoorma vähendamiseks Kalevi Norra toiduainekontsernile Orkla. Kalevi ja Tere müümine oli tal plaanis ka 2007. aastal, kui Indrek Rohumaa juhitud investeerimisfirma Alta Capital pidi need ära ostma

  6. Spectrophotometric Determination of Iron(II after Solid Phase Extraction of Its 2,2′ Bipyridine Complex on Silica Gel-Polyethylene Glycol

    Directory of Open Access Journals (Sweden)

    Nahid Pourreza


    Full Text Available A new solid phase extraction procedure was developed for preconcentration of iron(II using silica gel-polyethylene glycol (silica-PEG as an adsorbent. The method is based on retention of iron(II as 2,2′ bipyridine complex on silica-PEG. The retained complex is eluted by 1.0 mol L−1 of sulfuric acid-acetone mixture (1:2 and its absorbance is measured at 518 nm, spectrophotometrically. The effects of different parameters such as pH, concentration of the reagent, eluting reagent, sample volume, amount of adsorbent, and interfering ions were investigated. The calibration graph was linear in the range of 1–60 ng mL−1 of iron(II. The limit of detection based on 3Sb was 0.57 ng mL−1 and relative standard deviations (R.S.D for ten replicate measurements of 12 and 42 ng mL−1 of iron(II were 2.4 and 1.7%, respectively. The method was applied to the determination of of iron(II in water, multivitamin tablet, and spinach samples.

  7. 1D Piezoelectric Material Based Nanogenerators: Methods, Materials and Property Optimization. (United States)

    Li, Xing; Sun, Mei; Wei, Xianlong; Shan, Chongxin; Chen, Qing


    Due to the enhanced piezoelectric properties, excellent mechanical properties and tunable electric properties, one-dimensional (1D) piezoelectric materials have shown their promising applications in nanogenerators (NG), sensors, actuators, electronic devices etc. To present a clear view about 1D piezoelectric materials, this review mainly focuses on the characterization and optimization of the piezoelectric properties of 1D nanomaterials, including semiconducting nanowires (NWs) with wurtzite and/or zinc blend phases, perovskite NWs and 1D polymers. Specifically, the piezoelectric coefficients, performance of single NW-based NG and structure-dependent electromechanical properties of 1D nanostructured materials can be respectively investigated through piezoresponse force microscopy, atomic force microscopy and the in-situ scanning/transmission electron microcopy. Along with the introduction of the mechanism and piezoelectric properties of 1D semiconductor, perovskite materials and polymers, their performance improvement strategies are summarized from the view of microstructures, including size-effect, crystal structure, orientation and defects. Finally, the extension of 1D piezoelectric materials in field effect transistors and optoelectronic devices are simply introduced.

  8. Hypovitaminosis D increases TB co-infection risk on HIV patients (United States)

    Gayatri, Y. A. A. A.; Sukmawati, D. D.; Utama, S. M.; Somia, I. K. A.; Merati, T. P.


    Tuberculosis is causes of mortality and morbidity in patients with HIV. Hypovitaminosis D, a defective cell-mediated immune response to Mycobacterium tuberculosis infection has been extensively described in HIV patients, but studies assessing the role of vitamin D in TB-HIV co-infection are lacking. We, therefore, conducted a 1:1 pair- matched case-control study to verify hypovitaminosis D possible risk factor of TB- HIV co- infection. Consecutive HIV patients starting ARV and sex, age and CD4 cell count matched were by recruiting. Tuberculosis has confirmed by thepresence of acid-fast bacilli in sputum or mycobacterium detected in specimens culture/Gene Xpert/PCR. Vitamin D levels were by measuring direct chemiluminescent immunoassay on a LIAISON®25OH analyzer. The study comprised 25 cases and 25 controls, median (interquartile range) 25(OH)D3 serum concentration were 19.80 (12.15-27.45) ng/mL in cases and 33.30 (27.2-39.4) ng/mL in controls (PHIV patients.(OR 26.154 (90% CI: 4.371-156.541); p HIV co-infection.

  9. Realization of 7-cell hollow-core photonic crystal fibers with low loss in the region between 1.4 μm and 2.3 μm

    DEFF Research Database (Denmark)

    Lyngsøe, Jens Kristian; Mangan, Brian Joseph; Jakobsen, C.


    Five 7-cell core hollow-core fibers with photonic bandgap spectral positions between 1.4 μm and 2.3 μm were fabricated. The loss follows the ≈ λ-3 dependency previously reported [1] with a minimum measured loss of 9.5 dB/km at 1992 nm.......Five 7-cell core hollow-core fibers with photonic bandgap spectral positions between 1.4 μm and 2.3 μm were fabricated. The loss follows the ≈ λ-3 dependency previously reported [1] with a minimum measured loss of 9.5 dB/km at 1992 nm....

  10. Supplemental vitamin D and physical performance in COPD: a pilot randomized trial

    Directory of Open Access Journals (Sweden)

    Bjerk SM


    Full Text Available Sonja M Bjerk,1 Bradley D Edgington,1 Thomas S Rector,1,2 Ken M Kunisaki1,21University of Minnesota, 2Minneapolis VA Health Care System, Minneapolis, MN, USABackground: Low 25-hydroxyvitamin D (25[OH]D levels, commonly observed in chronic obstructive pulmonary disease (COPD, are associated with muscle weakness in elderly populations, and vitamin D supplementation appears to improve muscle strength and decrease falls in older individuals. We tested the effect of vitamin D supplementation on physical performance in patients with COPD.Methods: Patients were randomized to daily cholecalciferol (2000 IU or placebo for 6 weeks. The primary outcome was the 6-week change in Short Physical Performance Battery (SPPB score. Secondary outcomes included changes in the St George’s Respiratory Questionnaire (SGRQ score, and serum 25(OHD.Results: Thirty-six participants (mean age 68 years, all Caucasian males, mean forced expiratory volume in one second 33% of predicted completed the study. Despite an increase in 25(OHD levels in the intervention arm to a mean of 32.6 ng/mL (versus 22.1 ng/mL in the placebo arm, there was no difference in improvements in either SPPB scores (0.3 point difference; 95% confidence interval -0.8 to 1.5; P = 0.56 or SGRQ scores (2.3 point difference; 95% confidence interval -2.3 to 6.9; P = 0.32.Conclusion: Among patients with severe COPD, 2000 IU of daily vitamin D for 6 weeks increased 25(OHD to a level widely considered as normal. However, compared with placebo, short-term vitamin D supplementation had no discernible effect on a simple measure of physical performance.Keywords: chronic obstructive pulmonary disease, randomized controlled trial, vitamin D, skeletal muscle strength

  11. Assessment of airborne soy-hull allergen (Gly m 1) in the Port of Ancona, Italy. (United States)

    Antonicelli, L; Ruello, M L; Monsalve, R I; González, R; Fava, G; Bonifazi, F


    Epidemic asthma outbreaks are potentially a very high-risk medical situation in seaport towns where large volumes of soybean are loaded and unloaded Airborne allergen assessment plays a pivotal role in evaluating the resulting environmental pollution. The aim of this study was to measure the airborne Gly m 1 allergen level in the seaport of Ancona in order assess the soybean-specific allergenic risk for the city. Allergen and PM10 were evaluated at progressive distances from the port area. Allergen analysis was performed by monoclonal antibody-based immunoassay on the sampled filters. Daily meteorological data were obtained from the local meteorological station. For estimating the assimilative capacity of the atmosphere, an approach based on dispersive ventilation coefficient was tried. The allergen concentrations detected were low (range = 0.4-171 ng/m3). A decreasing gradient of the airborne allergen from the unloading area (22.1 +/- 41.2 ng/m3) to the control area (0.6 +/- 0.7 ng/m3) was detected. The concentration of the airborne Gly m 1 was not coupled with the presence of the soy-carrying ships in the port. A statistically significant relationship between airborne allergen, PM10 and local meteorological parameters quantifies the association with the atmospheric condition. Airborne Gly m 1 is part of the atmospheric dust of Ancona. The low level of this allergen seems consistent with the absence of asthma epidemic outbreak.

  12. A pooled analysis of CYP2D6 genotype in breast cancer prevention trials of low-dose tamoxifen. (United States)

    Johansson, Harriet; Gandini, Sara; Serrano, Davide; Gjerde, Jennifer; Lattanzi, Monia; Macis, Debora; Guerrieri-Gonzaga, Aliana; Aristarco, Valentina; Mellgren, Gunnar; Lien, Ernst; DeCensi, Andrea; Bonanni, Bernardo


    Decreased CYP2D6 activity is associated with lower levels of active tamoxifen metabolites. We examined the impact of CYP2D6 genotype on tamoxifen pharmacokinetics, biomarker activity, and efficacy in a pooled analysis of low-dose tamoxifen. Four randomized breast cancer prevention trials of very-low-dose (1 mg/day, n = 52 or 10 mg/week, n = 152) or low-dose tamoxifen (5 mg/day, n = 171) were pooled. DNA from 367 subjects was genotyped for CYP2D6 alleles associated with absent (PM allele: *3, *4, *5, *6, *7, *8, *12, and *14), reduced (IM allele: *9, *10, *17, *29, *41), normal (EM allele), or increased (UM: *XN) enzyme activity. Associations of tamoxifen, metabolites, activity biomarkers, and event-free survival with rapid (UM/EM, UM/IM, EM/EM, EM/IM, or EM/PM alleles) versus slow metabolizers (PM/IM or PM/PM) were investigated through random effects models, with 'study' as the random factor, and Cox regression models, adjusting for confounders. Rapid metabolizers had higher endoxifen levels than slow metabolizers: 15.3 versus 12.2 ng/mL (P = 0.018) with 5 mg/day, and 3.8 versus 2.8 ng/mL (P = 0.004) with 1 mg/day or 10 mg/week tamoxifen. The IGF-I decrease correlated with endoxifen (P = 0.002) and 4-hydroxytamoxifen levels, demonstrating steeper decreases at higher metabolite levels (P = 0.001). After a median follow-up of 12 years, rapid metabolizers with prior history of breast neoplasms allocated to tamoxifen 5 mg/day had a 60 % reduction of risk of recurrences (HR = 0.40, 95 % CI: 0.16-0.99) compared to slow metabolizers. CYP2D6 genotype may have an impact on tamoxifen efficacy at low doses. Trials investigating tamoxifen dose adjustments based on the woman's hormonal context and CYP2D6 genotype are warranted.

  13. Cocaine modulates allosteric D21 receptor-receptor interactions on dopamine and glutamate nerve terminals from rat striatum. (United States)

    Beggiato, Sarah; Borelli, Andrea Celeste; Borroto-Escuela, Dasiel; Corbucci, Ilaria; Tomasini, Maria Cristina; Marti, Matteo; Antonelli, Tiziana; Tanganelli, Sergio; Fuxe, Kjell; Ferraro, Luca


    The effects of nanomolar cocaine concentrations, possibly not blocking the dopamine transporter activity, on striatal D 21 heteroreceptor complexes and their inhibitory signaling over Gi/o, have been tested in rat striatal synaptosomes and HEK293T cells. Furthermore, the possible role of σ 1 receptors (σ 1 Rs) in the cocaine-provoked amplification of D 2 receptor (D 2 R)-induced reduction of K + -evoked [ 3 H]-DA and glutamate release from rat striatal synaptosomes, has also been investigated. The dopamine D 2 -likeR agonist quinpirole (10nM-1μM), concentration-dependently reduced K + -evoked [ 3 H]-DA and glutamate release from rat striatal synaptosomes. The σ 1 R antagonist BD1063 (100nM), amplified the effects of quinpirole (10 and 100nM) on K + -evoked [ 3 H]-DA, but not glutamate, release. Nanomolar cocaine concentrations significantly enhanced the quinpirole (100nM)-induced decrease of K + -evoked [ 3 H]-DA and glutamate release from rat striatal synaptosomes. In the presence of BD1063 (10nM), cocaine failed to amplify the quinpirole (100nM)-induced effects. In cotransfected σ 1 R and D 2L R HEK293T cells, quinpirole had a reduced potency to inhibit the CREB signal versus D 2L R singly transfected cells. In the presence of cocaine (100nM), the potency of quinpirole to inhibit the CREB signal was restored. In D 2L singly transfected cells cocaine (100nM and 10μM) exerted no modulatory effects on the inhibitory potency of quinpirole to bring down the CREB signal. These results led us to hypothesize the existence of functional D 21 R complexes on the rat striatal DA and glutamate nerve terminals and functional D 21 R-DA transporter complexes on the striatal DA terminals. Nanomolar cocaine concentrations appear to alter the allosteric receptor-receptor interactions in such complexes leading to enhancement of Gi/o mediated D 2 R signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. 1-[3-(4-Butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1) as a Model for the Rational Design of a Novel Class of Brain Penetrant Ligands with High Affinity and Selectivity for Dopamine D4 Receptor. (United States)

    Del Bello, Fabio; Bonifazi, Alessandro; Giorgioni, Gianfabio; Cifani, Carlo; Micioni Di Bonaventura, Maria Vittoria; Petrelli, Riccardo; Piergentili, Alessandro; Fontana, Stefano; Mammoli, Valerio; Yano, Hideaki; Matucci, Rosanna; Vistoli, Giulio; Quaglia, Wilma


    In the present article, the M 1 mAChR bitopic agonist 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1, 1) has been demonstrated to show unexpected D 4 R selectivity over D 2 R and D 3 R and to behave as a D 4 R antagonist. To better understand the structural features required for the selective interaction with the D 4 R and to obtain compounds unable to activate mAChRs, the aliphatic butyl chain and the piperidine nucleus of 1 were modified, affording compounds 2-14. The 4-benzylpiperidine 9 and the 4-phenylpiperazine 12 showed high D 4 R affinity and selectivity not only over the other D 2 -like subtypes, but also over M 1 -M 5 mAChRs. Derivative 12 was also highly selective over some selected off-targets. This compound showed biased behavior, potently and partially activating G i protein and inhibiting β-arrestin2 recruitment in functional studies. Pharmacokinetic studies demonstrated that it was characterized by a relevant brain penetration. Therefore, 12 might be a useful tool to better clarify the role played by D 4 R in disorders in which this subtype is involved.

  15. The Escape of Sisyphus or What “Post NG-PON2” Should Do Apart from Neverending Capacity Upgrades

    Directory of Open Access Journals (Sweden)

    Martin Maier


    Full Text Available The primary design goal of (revolutionary NG-PON1&2 was the provisioning of an ever increasing capacity to cope with video-dominated traffic and handle the explosion of mobile data traffic by means of offloading. Recently, however, questions on the future of “post NG-PON2” have surfaced whether to shift its research focus to business and operation related aspects and move access technology into a substantially different direction than continued capacity upgrades. In fact, recent studies indicate that ultimately the major factor limiting the performance of 4G mobile networks is latency rather than capacity of the backhaul. In this paper, we review recently proposed low-latency techniques for NG-PONs that require architectural modifications at the remote node or distribution fiber level and highlight advanced network coding and real-time polling based low-latency techniques that can be implemented in software, enable NG-PONs to carry higher traffic loads and thereby extend their lifetime, and maintain the passive nature of existent optical distribution networks. Furthermore, we elaborate on emerging trends and open challenges for future post NG-PON2 research. To better understand their true potential, we put them into a wider non-technical and historical perspective leading up to a sustainable Third Industrial Revolution (TIR economy and its underlying Energy Internet.

  16. 4d N=1 from 6d (1,0)

    Energy Technology Data Exchange (ETDEWEB)

    Razamat, Shlomo S. [Physics Department, Technion,Haifa, 32000 (Israel); Vafa, Cumrun [Jefferson Physical Laboratory, Harvard University,Cambridge, MA 02138 (United States); Zafrir, Gabi [Physics Department, Technion,Haifa, 32000 (Israel); Kavli IPMU (WPI), UTIAS, the University of Tokyo,Kashiwa, Chiba 277-8583 (Japan)


    We study the geometry of 4d N=1 SCFT’s arising from compactification of 6d (1,0) SCFT’s on a Riemann surface. We show that the conformal manifold of the resulting theory is characterized, in addition to moduli of complex structure of the Riemann surface, by the choice of a connection for a vector bundle on the surface arising from flavor symmetries in 6d. We exemplify this by considering the case of 4d N=1 SCFT’s arising from M5 branes probing ℤ{sub k} singularity compactified on a Riemann surface. In particular, we study in detail the four dimensional theories arising in the case of two M5 branes on ℤ{sub 2} singularity. We compute the conformal anomalies and indices of such theories in 4d and find that they are consistent with expectations based on anomaly and the moduli structure derived from the 6 dimensional perspective.

  17. Syntheses, crystal structures and luminescent properties of two new 1D d 1 coordination polymers constructed from 2,2'-bibenzimidazole and 1,4-benzenedicarboxylate

    International Nuclear Information System (INIS)

    Wen Lili; Li Yizhi; Dang Dongbin; Tian Zhengfang; Ni Zhaoping; Meng Qingjin


    Two novel interesting d 1 metal coordination polymers, [Zn(H 2 bibzim)(BDC)] n (1) and [Cd(H 2 bibzim)(BDC)] n (2) [H 2 bibzim=2,2'-bibenzimidazole, BDC=1,4-benzenedicarboxylate] have been synthesized under solvothermal conditions and structurally characterized. Both 1 and 2 are constructed from infinite neutral zigzag-like one-dimensional (1D) chains. The π-π interactions and interchain hydrogen-bonding interactions further extend the 1D arrangement to generate a 3D supramolecular architecture for 1 and 2. Both complexes have high thermal stability and display strong blue fluorescent emissions in the solid state upon photo-excitation at 365 nm at room temperature. They are the first two examples that 2,2'-bibenzimidazole has been introduced into the d 1 coordination polymeric framework

  18. Characterization and therapeutic evaluation of a Nestin⁺ CNP⁺ NG2⁺ cell population on mouse spinal cord injury. (United States)

    Liu, Rui; Zhang, Si; Yang, Haijie; Ju, Peijun; Xia, Yinyan; Shi, Yu; Lim, Tse Hui; Lim, Alvin St; Liang, Fengyi; Feng, Zhiwei


    The NG2 chondroitin sulfate proteoglycan-expressing neural cells (NG2 cells) have originally been considered as oligodendrocyte progenitor cells (OPCs). However, recent findings on their diverse functions and lineage heterogeneity demonstrated that the NG2 cells contain various sub-populations whose concrete features and therapeutic potential yet remained elucidated. In the present study, we characterized a Nestin(+) 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP)(+) NG2(+) subpopulation from embryonic rat cerebral cortex. The Nestin(+) CNP(+) NG2(+) cells exhibited remarkable progenitor characteristics. Having been immortalized by human telomerase reverse transcriptase (hTERT), the life span of Nestin(+) CNP(+) NG2(+) cells was extended to 230 population doublings (PDs). With immortalized NG2 cells, we demonstrated their differentiation capacities to oligodendrocytes, astrocytes and neurons. Furthermore, transplanted into injured spinal cord of a mouse model, they were able to promote remyelination and neuronal regeneration, thereby enhancing the functional recovery. Our findings suggest that the Nestin(+) CNP(+) NG2(+) progenitor cells could be a good alternative cell source of cell therapy for neurological disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Attributing Methane and Carbon Dioxide Emissions from Anthropogenic and Natural Sources Using AVIRIS-NG (United States)

    Thorpe, A. K.; Frankenberg, C.; Thompson, D. R.; Duren, R. M.; Aubrey, A. D.; Bue, B. D.; Green, R. O.; Gerilowski, K.; Krings, T.; Borchardt, J.; Kort, E. A.; Sweeney, C.; Conley, S. A.; Roberts, D. A.; Dennison, P. E.; Ayasse, A.


    Imaging spectrometers like the next generation Airborne Visible/Infrared Imaging Spectrometer (AVIRIS-NG) can map large regions with the high spatial resolution necessary to resolve methane (CH4) and carbon dioxide (CO2) emissions. This capability is aided by real time detection and geolocation of gas plumes, permitting unambiguous identification of individual emission source locations and communication to ground teams for rapid follow up. We present results from AVIRIS-NG flight campaigns in the Four Corners region (Colorado and New Mexico) and the San Joaquin Valley (California). Over three hundred plumes were observed, reflecting emissions from anthropogenic and natural sources. Examples of plumes will be shown for a number of sources, including CH4 from well completions, gas processing plants, tanks, pipeline leaks, natural seeps, and CO2 from power plants. Despite these promising results, an imaging spectrometer built exclusively for quantitative mapping of gas plumes would have improved sensitivity compared to AVIRIS-NG. For example, an instrument providing a 1 nm spectral sampling (2,000-2,400 micron) would permit mapping CH4, CO2, H2O, CO, and N2O from more diffuse sources using both airborne and orbital platforms. The ability to identify emission sources offers the potential to constrain regional greenhouse gas budgets and improve partitioning between anthropogenic and natural emission sources. Because the CH4 lifetime is only about 9 years and CH4 has a Global Warming Potential 86 times that of CO2 for a 20 year time interval, mitigating these emissions is a particularly cost-effective approach to reduce overall atmospheric radiative forcing. Fig. 1. True color image subset with superimposed gas plumes showing concentrations in ppmm. Left: AVIRIS-NG observed CH4 plumes from natural gas processing plant extending over 500 m downwind of multiple emissions sources. Right: Multiple CO2 plumes observed from coal-fired power plant.

  20. 1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane and tris(methylphenyl) phosphate cause significant effects on development, mRNA expression, and circulating bile acid concentrations in chicken embryos

    Energy Technology Data Exchange (ETDEWEB)

    Crump, Doug, E-mail: [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Porter, Emily; Egloff, Caroline; Williams, Kim L.; Letcher, Robert J.; Gauthier, Lewis T. [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Kennedy, Sean W. [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5 (Canada)


    1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane (DBE-DBCH; formerly abbreviated as TBECH) and tris(methylphenyl) phosphate (TMPP; formerly abbreviated as TCP) are additive flame retardants that are detected in the environment and biota. A recent avian in vitro screening study of 16 flame retardants identified DBE-DBCH and TMPP as important chemicals for follow-up in ovo evaluation based on their effects on cytotoxicity and mRNA expression in avian hepatocytes. In this study, technical mixtures of DBE-DBCH and TMPP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 54,900 ng/g and from 0 to 261,400 ng/g, respectively, to determine effects on pipping success, development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations. Both compounds were detectable in embryos at pipping and the β-DBE-DBCH isomer was depleted more rapidly than the α-isomer in tissue samples. DBE-DBCH had limited effects on the endpoints measured, with the exception of the up-regulation of two phase I metabolizing enzymes, CYP3A37 and CYP2H1. TMPP exposure caused embryonic deformities, altered growth, increased liver somatic index (LSI) and plasma bile acid concentrations, and altered mRNA expression levels of genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Overall, TMPP elicited more adverse molecular and phenotypic effects than DBE-DBCH albeit at concentrations several orders of magnitude greater than those detected in the environment. The increase in plasma bile acid concentrations was a useful phenotypic anchor as it was associated with a concomitant increase in LSI, discoloration of the liver tissue, and modulation of hepatic genes involved with xenobiotic and lipid metabolism. - Highlights: • DBE-DBCH and TMPP are not embryolethal to chicken embryos. • TMPP caused deformities, morphometric alterations, and increased plasma bile acids. • DBE-DBCH and TMPP altered mRNA levels

  1. Vitamin D metabolites in human milk

    International Nuclear Information System (INIS)

    Weisman, Y.; Bawnik, J.C.; Eisenberg, Z.; Spirer, Z.


    The concentrations of unconjugated 25-OHD, 24, 25(OH)2D, and 1,25(OH)2D were measured in human milk by competitive protein-binding radioassays following successive preparative Sephadex LH-20 chromatography and HPLC. The mean (+/- SE) concentration of 25-OHD was 0.37 +/- 0.03 ng/ml, of 24,25(OH)2D was 24.8 +/- 1.9 pg/ml, and of 1,25(OH)2D was 2.2 +/-0.1 pg/ml. The concentration of 25-OHD3 in milk as determined by HPLC and UV detection at 254 nm was 0.27 +/- 0.08 ng/ml. The milk concentrations of vitamin D metabolites did not correlate with the maternal serum 25-OHD levels. The total amounts of unconjugated vitamin D metabolites correspond to the known low bioassayable vitamin D antirachitic activity in human milk

  2. Vitamin D in health and disease. (United States)

    Heaney, Robert P


    Vitamin D functions in the body through both an endocrine mechanism (regulation of calcium absorption) and an autocrine mechanism (facilitation of gene expression). The former acts through circulating calcitriol, whereas the latter, which accounts for more than 80% of the metabolic utilization of the vitamin each day, produces, uses, and degrades calcitriol exclusively intracellularly. In patients with end-stage kidney disease, the endocrine mechanism is effectively disabled; however, the autocrine mechanism is able to function normally so long as the patient has adequate serum levels of 25(OH)D, on which its function is absolutely dependent. For this reason, calcitriol and its analogs do not constitute adequate replacement in managing vitamin D needs of such patients. Optimal serum 25(OH)D levels are greater than 32 ng/mL (80 nmol/L). The consequences of low 25(OH)D status include increased risk of various chronic diseases, ranging from hypertension to diabetes to cancer. The safest and most economical way to ensure adequate vitamin D status is to use oral dosing of native vitamin D. (Both daily and intermittent regimens work well.) Serum 25(OH)D can be expected to rise by about 1 ng/mL (2.5 nmol/L) for every 100 IU of additional vitamin D each day. Recent data indicate that cholecalciferol (vitamin D(3)) is substantially more potent than ergocalciferol (vitamin D(2)) and that the safe upper intake level for vitamin D(3) is 10,000 IU/d.

  3. Quantitative studies of the brain specific antigens GFA, 14-3-2, synaptin C1, D1, D2, D3 and D5 in jimpy mouse

    DEFF Research Database (Denmark)

    Jacque, C M; Baumann, N A; Bock, E


    Seven antigens specific to the nervous tissue were measured in both Jimpy and control mice. The D5 and the GFA protein, both components of the glia, are strongly increased in the mutant while the neuronal components 14-3-2, synaptin C1, D1, D2 and D3 are unchanged....

  4. Vitamin D deficiency in Korean children: prevalence, risk factors, and the relationship with parathyroid hormone levels

    Directory of Open Access Journals (Sweden)

    In Hyuk Chung


    Full Text Available PurposeThis study was performed to investigate the relationship between serum vitamin D and parathyroid hormone (PTH levels as well as to describe the prevalence and the risk factors of vitamin D deficiency (VDD in Korean children.MethodsParticipants were 1,212 children aged 4 to 15 years, who visited Bundang CHA Medical Center (located at 37°N between March 2012 and February 2013. Overweight was defined as body mass index≥85th percentile. Participants were divided into 4 age groups and 2 seasonal groups. VDD was defined by serum 25-hydroxyvitamin D (25OHD <20 ng/mL.ResultsThe level of 25OHD was significantly lower in overweight group than in normal weight group (17.1±5.1 ng/mL vs. 19.1±6.1 ng/mL, P<0.001. Winter-spring season (odds ratio [OR], 4.46; 95% confidence interval [CI], 3.45-5.77, older age group (OR, 1.60; 95% CI, 1.36-1.88, and overweight (OR, 2.21; 95% CI, 1.62-3.01 were independently related with VDD. The PTH levels were significantly higher in VDD group compared to vitamin D insufficiency and sufficiency group (P<0.001. In normal weight children, 25OHD (β=-0.007, P<0.001 and ionized calcium (β=-0.594, P=0.007 were independently related with PTH, however, these associations were not significant in overweight children.ConclusionVDD is very common in Korean children and its prevalence increases in winter-spring season, in overweight children and in older age groups. Further investigation on the vitamin D and PTH metabolism according to adiposity is required.

  5. Mechanical Stimulation and IGF-1 Enhance mRNA Translation Rate in Osteoblasts Via Activation of the AKT-mTOR Pathway. (United States)

    Bakker, Astrid D; Gakes, Tom; Hogervorst, Jolanda M A; de Wit, Gerard M J; Klein-Nulend, Jenneke; Jaspers, Richard T


    Insulin-like growth factor-1 (IGF-1) is anabolic for muscle by enhancing the rate of mRNA translation via activation of AKT and subsequent activation of the mammalian target of rapamycin complex 1 (mTOR), thereby increasing cellular protein production. IGF-1 is also anabolic for bone, but whether the mTOR pathway plays a role in the rate of bone matrix protein production by osteoblasts is unknown. We hypothesized that anabolic stimuli such as mechanical loading and IGF-1 stimulate protein synthesis in osteoblasts via activation of the AKT-mTOR pathway. MC3T3-E1 osteoblasts were either or not subjected for 1 h to mechanical loading by pulsating fluid flow (PFF) or treated with or without human recombinant IGF-1 (1-100 ng/ml) for 0.5-6 h, to determine phosphorylation of AKT and p70S6K (downstream of mTOR) by Western blot. After 4 days of culture with or without the mTOR inhibitor rapamycin, total protein, DNA, and gene expression were quantified. IGF-1 (100 ng/ml) reduced IGF-1 gene expression, although PFF enhanced IGF-1 expression. IGF-1 did not affect collagen-I gene expression. IGF-1 dose-dependently enhanced AKT and p70S6K phosphorylation at 2 and 6 h. PFF enhanced phosphorylation of AKT and p70S6K already within 1 h. Both IGF-1 and PFF enhanced total protein per cell by ∼30%, but not in the presence of rapamycin. Our results show that IGF-1 and PFF activate mTOR, thereby stimulating the rate of mRNA translation in osteoblasts. The known anabolic effect of mechanical loading and IGF-1 on bone may thus be partly explained by mTOR-mediated enhanced protein synthesis in osteoblasts. © 2015 Wiley Periodicals, Inc.

  6. A proposal for M2-brane-anti-M2-brane action

    International Nuclear Information System (INIS)

    Garousi, Mohammad R.


    We propose a manifestly SO(8) invariant BF type Lagrangian for describing the dynamics of M2-brane-anti-M2-brane system in flat spacetime. When one of the scalars which satisfies a free-scalar equation takes a large expectation value, the M2-brane-anti-M2-brane action reduces to the tachyon DBI action of D2-brane-anti-D2-brane system in flat spacetime.


    Directory of Open Access Journals (Sweden)

    Mintareja Teguh


    Full Text Available Objective: To determine the role of protein-with-molecular-weight-53 (p53, burkit cell lymphoma 2 (Bcl2, Fas ligand (FasL mRNA, and vascular cell adhesion molecule 1 (VCAM-1, known as the apoptosis-related molecular pathway, in preeclamptic patients. Methods: Observation on the correlation between the mRNA levels of p53, Bcl2 and FasL and VCAM-1 in 31 subjects at 28-42 weeks gestational age was performed in this study using the real time reverse transcriptase-polymerase chain reaction (RT-PCR. Results: The results showed that p53 mRNA increased (>1.2350 ng/μL in the preeclampsia group compared to the normal pregnancy group (p=0.010, Bcl2 mRNA was lower (≤0.9271 ng/μL in the preeclampsia group than the control group (p=0.041. There was also a tendency of increased FasL mRNA expression (>0.5509 ng/μL in the preeclampsia group compared to the normal pregnancy group (p=0.300. The level of VCAM-1 elevated (>890.08 ng/mL in the preeclampsia group compared to the normal pregnancy group (p=0.001. In preeclampsia, the correlation between the Bcl2/p53 ratio and VCAM-1 was r=0.541 (p=0.002, whereas the correlation in normal pregnancy was r=0.099 (p=0.595. Conclusions: There are correlations between the mRNA expression levels of p53 and Bcl2 as an intrinsic pathway of apoptosis along with the VCAM-1 levels in the incidence of preeclampsia. However, no correlation is found between FasL mRNA expression and the incidence of preeclampsia.

  8. Vitamin D levels and microvascular complications in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Sarita Bajaj


    Full Text Available Background: Vitamin D has important actions on glucose metabolism. These include improved insulin exocytosis, direct stimulation of insulin receptor, improved uptake of glucose by peripheral tissues, improving insulin resistance. It has got various pleiotropic effects like suppression of cell mediated immunity, regulation of cell proliferation, stimulation of neurotropic factors such as nerve growth factor, Glial cell line-derived neurotrophic factor, neurotropin, suppression of RAAS, reduction of albuminuria, immunomodulatory effects, and anti-inflammatory effects. Thus, vitamin D is implicated in many ways in the pathogenesis of retinopathy, neuropathy and nephropathy. Objectives: To study the correlation of vitamin D levels with microvascular complications in type 2 diabetes. Materials and Methods: Cross-sectional case-control study of 18 patients (18-70 years, who met the American Diabetes Association 2011 criteria for type 2 diabetes, was conducted. Age and sex matched healthy controls were taken. Subjects were evaluated for the presence of microvascular complications by clinical evaluation, urine examination, fundus examination, nerve conduction studies, and various biochemical tests. 25-OH cholecalciferol levels were done for each. Cut off level for vitamin D deficiency was 20 ng/ml. Results: Mean vitamin D was lower in type 2 diabetics than healthy subjects (19.046 vs. 27.186 ng/ml. Prevalence of vitamin D deficiency and insufficiency was found to significantly higher in diabetics when compared to healthy subjects (P = 0.0001. Vitamin D deficiency was found to be significantly associated with neuropathy (χ2 = 5.39, df = 1, P = 0.020, retinopathy, (χ2 = 6.6, df = 1, P = 0.010 and nephropathy (χ2 = 10. 52, df = 1, P = 0.001. Lower levels of vitamin D were found to be associated with increasing prevalence of combinations of microvascular complications namely neuropathy with retinopathy (P = 0.036, neuropathy with nephropathy (P = 0

  9. Assay of 25-OH vitamin D3

    International Nuclear Information System (INIS)

    Nayer, P. de; Thalasso, M.; Beckers, C.


    A simplified version of the competitive protein binding assay for 25-OH vit D3 derived from the method of Belsey et al. is presented. The procedure does not include a chromatography step, and is performed on an alcoolic extract of 0.1 ml plasma or serum. Normal rat serum (1:20,000) was used as binding protein. No β-lipoproteins were added to the assay buffer. A 10% displacement of the tracer was observed at 0.04 ng/tube, and 50% at 0.15 ng/tube, allowing for the measurement of 25-OH vit D3 concentrations between 2 ng/ml and 200 ng/ml. Mean values in a normal group was 23.1 +- 6.5 ng/ml (range 16-37 ng/ml, n = 11). (orig.) [de

  10. 26 CFR 1.401(m)-2 - ACP test. (United States)


    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false ACP test. 1.401(m)-2 Section 1.401(m)-2 Internal... TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(m)-2 ACP test. (a) Actual contribution percentage (ACP) test—(1) In general—(i) ACP test formula. A plan satisfies the ACP test for a plan year only...

  11. Atmospheric partitioning and the air-water exchange of polycyclic aromatic hydrocarbons in a large shallow Chinese lake (Lake Chaohu). (United States)

    Qin, Ning; He, Wei; Kong, Xiang-Zhen; Liu, Wen-Xiu; He, Qi-Shuang; Yang, Bin; Ouyang, Hui-Ling; Wang, Qing-Mei; Xu, Fu-Liu


    The residual levels of polycyclic aromatic hydrocarbons (PAHs) in the atmosphere and in dissolved phase from Lake Chaohu were measured by (GC-MS). The composition and seasonal variation were investigated. The diffusive air-water exchange flux was estimated by a two-film model, and the uncertainty in the flux calculations and the sensitivity of the parameters were evaluated. The following results were obtained: (1) the average residual levels of all PAHs (PAH16) in the atmosphere from Lake Chaohu were 60.85±46.17 ng m(-3) in the gaseous phase and 14.32±23.82 ng m(-3) in the particulate phase. The dissolved PAH16 level was 173.46±132.89 ng L(-1). (2) The seasonal variation of average PAH16 contents ranged from 43.09±33.20 ng m(-3) (summer) to 137.47±41.69 ng m(-3) (winter) in gaseous phase, from 6.62±2.72 ng m(-3) (summer) to 56.13±22.99 ng m(-3) (winter) in particulate phase, and 142.68±74.68 ng L(-1) (winter) to 360.00±176.60 ng L(-1) (summer) in water samples. Obvious seasonal trends of PAH16 concentrations were found in the atmosphere and water. The values of PAH16 for both the atmosphere and the water were significantly correlated with temperature. (3) The monthly diffusive air-water exchange flux of total PAH16 ranged from -1.77×10(4) ng m(-2) d(-1) to 1.11×10(5) ng m(-2) d(-1), with an average value of 3.45×10(4) ng m(-2) d(-1). (4) The results of a Monte Carlo simulation showed that the monthly average PAH fluxes ranged from -3.4×10(3) ng m(-2) d(-1) to 1.6×10(4) ng m(-2) d(-1) throughout the year, and the uncertainties for individual PAHs were compared. (5) According to the sensitivity analysis, the concentrations of dissolved and gaseous phase PAHs were the two most important factors affecting the results of the flux calculations. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Vitamin D Status in Patients With Stage IV Colorectal Cancer: Findings From Intergroup Trial N9741 (United States)

    Ng, Kimmie; Sargent, Daniel J.; Goldberg, Richard M.; Meyerhardt, Jeffrey A.; Green, Erin M.; Pitot, Henry C.; Hollis, Bruce W.; Pollak, Michael N.; Fuchs, Charles S.


    Purpose Previous studies have suggested that higher plasma 25-hydroxyvitamin D3 [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival, but the prevalence of vitamin D deficiency in advanced colorectal cancer and its influence on outcomes are unknown. Patients and Methods We prospectively measured plasma 25(OH)D levels in 515 patients with stage IV colorectal cancer participating in a randomized trial of chemotherapy. Vitamin D deficiency was defined as 25(OH)D lower than 20 ng/mL, insufficiency as 20 to 29 ng/mL, and sufficiency as ≥ 30 ng/mL. We examined the association between baseline 25(OH)D level and selected patient characteristics. Cox proportional hazards models were used to calculate hazard ratios (HR) for death, disease progression, and tumor response, adjusted for prognostic factors. Results Among 515 eligible patients, 50% of the study population was vitamin D deficient, and 82% were vitamin D insufficient. Plasma 25(OH)D levels were lower in black patients compared to white patients and patients of other race (median, 10.7 v 21.1 v 19.3 ng/mL, respectively; P < .001), and females compared to males (median, 18.3 v 21.7 ng/mL, respectively; P = .0005). Baseline plasma 25(OH)D levels were not associated with patient outcome, although given the distribution of plasma levels in this cohort, statistical power for survival analyses were limited. Conclusion Vitamin D deficiency is highly prevalent among patients with stage IV colorectal cancer receiving first-line chemotherapy, particularly in black and female patients. PMID:21422438

  13. Regulation of dopamine D2 receptors in a novel cell line (SUP1)

    International Nuclear Information System (INIS)

    Ivins, K.J.; Luedtke, R.R.; Artymyshyn, R.P.; Molinoff, P.B.


    A prolactin-secreting cell line, SUP1, has been established from rat pituitary tumor 7315a. In radioligand binding experiments, the D2 receptor antagonist (S)-(-)-3- 125 I iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2- pyrrolidinyl)methyl]benzamide ( 125 I IBZM) labeled a single class of sites in homogenates of SUP1 cells (Kd = 0.6 nM; Bmax = 45 fmol/mg of protein). The sites displayed a pharmacological profile consistent with that of D2 receptors. Inhibition of the binding of 125 I IBZM by dopamine was sensitive to GTP, suggesting that D2 receptors in SUP1 cells are coupled to guanine nucleotide-binding protein(s). In the presence of isobutylmethylxanthine, dopamine decreased the level of cAMP accumulation in SUP1 cells. Dopamine also inhibited prolactin secretion from SUP1 cells. Both the inhibition of cAMP accumulation and the inhibition of prolactin secretion were blocked by D2 receptor antagonists, suggesting that these effects of dopamine were mediated by an interaction with D2 receptors. The regulation of D2 receptors in SUP1 cells by D2 receptor agonists was investigated. Exposure of SUP1 cells to dopamine or to the D2 receptor agonist N-propylnorapomorphine led to increased expression of D2 receptors, with no change in the affinity of the receptors for 125 I IBZM. An increase in the density of D2 receptors in SUP1 cells was evident within 7 hr of exposure to dopamine. Spiroperidol, a D2 receptor antagonist, blocked the effect of dopamine on receptor density. These results suggest that exposure of D2 receptors in SUP1 cells to agonists leads to an up-regulation of D2 receptors. Dopamine retained the ability to inhibit cAMP accumulation in SUP1 cells exposed to dopamine for 24 hr, suggesting that D2 receptors in SUP1 cells are not desensitized by prolonged exposure to agonist

  14. ngVLA Cryogenic Subsystem Concept (United States)

    Wootten, Al; Urbain, Denis; Grammer, Wes; Durand, S.


    The VLA’s success over 35 years of operations stems in part from dramatically upgraded components over the years. The time has come to build a new array to lead the radio astronomical science into its next 40 years. To accomplish that, a next generation VLA (ngVLA) is envisioned to have 214 antennas with diameters of 18m. The core of the array will be centered at the current VLA location, but the arms will extend out to 1000km.The VLA cryogenic subsystem equipment and technology have remained virtually unchanged since the early 1980s. While adequate for a 27-antenna array, scaling the current system for an array of 214 antennas would be prohibitively expensive in terms of operating cost and maintenance. The overall goal is to limit operating cost to within three times the current level, despite having 8 times the number of antennas. To help realize this goal, broadband receivers and compact feeds will be utilized to reduce both the size and number of cryostats required. The current baseline front end concept calls for just two moderately-sized cryostats for the entire 1.2-116 GHz frequency range, as opposed to 8 in the VLA.For the ngVLA cryogenics, our objective is a well-optimized and efficient system that uses state-of-the-art technology to minimize per-antenna power consumption and maximize reliability. Application of modern technologies, such as variable-speed operation for the scroll compressors and cryocooler motor drives, allow the cooling capacity of the system to be dynamically matched to thermal loading in each cryostat. Significantly, power savings may be realized while the maintenance interval of the cryocoolers is also extended.Finally, a receiver designed to minimize thermal loading can produce savings directly translating to lower operating cost when variable-speed drives are used. Multi-layer insulation (MLI) on radiation shields and improved IR filters on feed windows can significantly reduce heat loading.Measurements done on existing cryogenic

  15. Aflatoxin M1 contamination of raw and pasteurized milk produced in Sanandaj, Iran

    Directory of Open Access Journals (Sweden)

    Mafakheri, Sh.


    Full Text Available This study was conducted to evaluate and compare the levels of aflatoxin M1 in raw and pasteurized milk samples during different seasons by Enzyme- Linked Immuno Sorbent Assay in Sanandaj, Iran. In 257 (94.49% out of 272 milk samples the presence of aflatoxin M1 was detected in concentrations ranging between 0.007 and 115.930 ng/l. AFM1 level in 12 (4.4% of positive samples were higher than the maximum tolerance limit (50 ng/l accepted by Iran and European Union countries. Statistical evaluations showed that the differences between raw and pasteurized samples were not significant (p<0.05. There was no significant difference between spring and summer but the differences between other seasons were statistically significant. Winter samples with 22.35 ng/l and summer samples with 5.14 ng/l had the highest and lowest concentration, respectively (p<0.05. Since contamination of milk with aflatoxin is a potential risk for human health, milk and milk products should be controlled periodically for Aflatoxin contamination.

  16. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Mário Henrique M Barros

    Full Text Available Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a

  17. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages. (United States)

    Barros, Mário Henrique M; Hauck, Franziska; Dreyer, Johannes H; Kempkes, Bettina; Niedobitek, Gerald


    Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool for

  18. The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum. (United States)

    Centonze, Diego; Rossi, Silvia; Napoli, Ilaria; Mercaldo, Valentina; Lacoux, Caroline; Ferrari, Francesca; Ciotti, Maria Teresa; De Chiara, Valentina; Prosperetti, Chiara; Maccarrone, Mauro; Fezza, Filomena; Calabresi, Paolo; Bernardi, Giorgio; Bagni, Claudia


    Dopamine D(2) receptor (D(2)DR)-mediated transmission in the striatum is remarkably flexible, and changes in its efficacy have been heavily implicated in a variety of physiological and pathological conditions. Although receptor-associated proteins are clearly involved in specific forms of synaptic plasticity, the molecular mechanisms regulating the sensitivity of D(2) receptors in this brain area are essentially obscure. We have studied the physiological responses of the D(2)DR stimulations in mice lacking the brain cytoplasmic RNA BC1, a small noncoding dendritically localized RNA that is supposed to play a role in mRNA translation. We show that the efficiency of D(2)-mediated transmission regulating striatal GABA synapses is under the control of BC1 RNA, through a negative influence on D(2) receptor protein level affecting the functional pool of receptors. Ablation of the BC1 gene did not result in widespread dysregulation of synaptic transmission, because the sensitivity of cannabinoid CB(1) receptors was intact in the striatum of BC1 knock-out (KO) mice despite D(2) and CB(1) receptors mediated similar electrophysiological actions. Interestingly, the fragile X mental retardation protein FMRP, one of the multiple BC1 partners, is not involved in the BC1 effects on the D(2)-mediated transmission. Because D(2)DR mRNA is apparently equally translated in the BC1-KO and wild-type mice, whereas the protein level is higher in BC1-KO mice, we suggest that BC1 RNA controls D(2)DR indirectly, probably regulating translation of molecules involved in D(2)DR turnover and/or stability.

  19. Breast Radiation Dose With CESM Compared With 2D FFDM and 3D Tomosynthesis Mammography. (United States)

    James, Judy R; Pavlicek, William; Hanson, James A; Boltz, Thomas F; Patel, Bhavika K


    We aimed to compare radiation dose received during contrast-enhanced spectral mammography (CESM) using high- and low-energy projections with radiation dose received during 2D full field digital mammography (FFDM) and 3D tomosynthesis on phantoms and patients with varying breast thickness and density. A single left craniocaudal projection was chosen to determine the doses for 6214 patients who underwent 2D FFDM, 3662 patients who underwent 3D tomosynthesis, and 173 patients who underwent CESM in this retrospective study. Dose measurements were also collected in phantoms with composition mimicking nondense and dense breast tissue. Average glandular dose (AGD) ± SD was 3.0 ± 1.1 mGy for CESM exposures at a mean breast thickness of 63 mm. At this thickness, the dose was 2.1 mGy from 2D FFDM and 2.5 mGy from 3D tomosynthesis. The nondense phantom had a mean AGD of 1.0 mGy with 2D FFDM, 1.3 mGy with 3D tomosynthesis, and 1.6 mGy with CESM. The dense breast phantom had a mean AGD of 1.3 mGy with 2D FFDM, 1.4 mGy with 3D tomosynthesis, and 2.1 mGy with CESM. At a compressed thickness of 4.5 cm, radiation exposure from CESM was approximately 25% higher in dense breast phantoms than in nondense breast phantoms. The dose in the dense phantom at a compressed thickness of 6 cm was approximately 42% higher than the dose in the nondense phantom at a compressed thickness of 4.5 cm. CESM was found to increase AGD at a mean breast thickness of 63 mm by approximately 0.9 mGy and 0.5 mGy compared with 2D FFDM and 3D tomosynthesis, respectively. Of note, CESM provides a standard image (similar to 2D FFDM) that is obtained using the low-energy projection. Overall, the AGD from CESM falls below the dose limit of 3 mGy set by Mammography Quality Standards Act regulations.

  20. IGF-1R mRNA expression is increased in obese children. (United States)

    Ricco, Rafaela Cristina; Ricco, Rubens Garcia; Queluz, Mariangela Carletti; de Paula, Mariana Teresa Sarti; Atique, Patricia Volpon; Custódio, Rodrigo José; Tourinho Filho, Hugo; Del Roio Liberatori, Raphael; Martinelli, Carlos Eduardo


    Obese children are often taller than age-matched subjects. Reports on GH and IGF-I levels in obese individuals are controversial, with normal and reduced GH-IGF-I levels having been reported in this group of patients. Thus, the aim of this study was to analyse insulin-like growth factor type 1 receptor (IGF-IR) mRNA expression in obese children. Forty-seven pre-pubertal children were included in this study: 29 were obese and taller than their target height, and 18 were normal eutrophic controls. Fasting blood samples were collected for IGF-IR mRNA expression in isolated lymphocytes and serum IGF-I, ALS, IGFBP-3, and IGFBP-1 concentration analysis. Relative IGF-IR gene expression (2 -ΔΔCT ) was significantly (P=0.025) higher in obese children (median 1.87) than in controls (1.15). Fourteen of the 29 obese subjects showed 2 -ΔΔCT values greater than or equal to 2, while only 2 individuals in the control group showed values above 2 (P=0.01). Obese children showed significantly (P=0.01) higher IGF-I concentrations than the control group (237ng/ml and 144ng/ml, respectively). Among obese patients, 65.5% had IGF-I values above the 75 percentile of the control group (P=0.02). ALS concentration was significantly (P=0.04) higher in the obese group, while IGFBP-3 levels were similar in obese and control children. IGFBP-1 concentration was lower in obese children, while insulin levels and HOMA-IR index were higher than in controls. The higher IGF-IR mRNA expression observed in obese children, associated with the higher IGF-I and ALS and the lower IGFBP-1 levels, suggest that the higher stature observed in these children may be due to increased IGF-I bioactivity. Copyright © 2017 Elsevier Ltd. All rights reserved.


    International Nuclear Information System (INIS)



    A271 COMPLETE SUPPRESSION OF THE M/N = 2/1 NEOCLASSICAL TEARING MODE USING RADIALLY LOCALIZED ELECTRON CYCLOTRON CURRENT DRIVE ON DIII-D AND THE REQUIREMENTS FOR ITER. DIII-D experiments demonstrate the first real-time feedback control of the relative location of a narrow beam of microwaves to completely suppress and eliminate a growing tearing mode at the q = 2 surface. long wavelength tearing modes such as the m/n = 2/1 instability are particularly deleterious to tokamak operation. Confinement is seriously degraded by the island, plasma rotation can cease (mode-lock) and disruption can occur. The neoclassical tearing mode (NTM) becomes unstable due to the presence of a helically-perturbed bootstrap current and can be stabilized by replacing the missing bootstrap current in the island O-point by precisely located co-electron cyclotron current drive (ECCD). The optimum position is found when the DIII-D plasma control system (PCS) is put into a search and suppress mode that makes small radial shifts (in about 1 cm steps) in the ECCD location based on minimizing the Mirnov amplitude. Requirements for ITER are addressed

  2. β-adrenergic-stimulated macrophages: Comprehensive localization in the M1M2 spectrum (United States)

    Lamkin, Donald M.; Ho, Hsin-Yun; Ong, Tiffany H.; Kawanishi, Carly K.; Stoffers, Victoria L.; Ahlawat, Nivedita; Ma, Jeffrey C.Y.; Arevalo, Jesusa M. G.; Cole, Steve W.; Sloan, Erica K.


    β-adrenergic signaling can regulate macrophage involvement in several diseases and often produces anti-inflammatory properties in macrophages, which are similar to M2 properties in a dichotomous M1 vs. M2 macrophage taxonomy. However, it is not clear that β-adrenergic-stimulated macrophages may be classified strictly as M2. In this in vitro study, we utilized recently published criteria and transcriptome-wide bioinformatics methods to map the relative polarity of murine β-adrenergic-stimulated macrophages within a wider M1M2 spectrum. Results show that β-adrenergic-stimulated macrophages did not fit entirely into any one predefined category of the M1M2 spectrum but did express genes that are representative of some M2 side categories. Moreover, transcript origin analysis of genome-wide transcriptional profiles located β-adrenergic-stimulated macrophages firmly on the M2 side of the M1M2 spectrum and found active suppression of M1 side gene transcripts. The signal transduction pathways involved were mapped through blocking experiments and bioinformatics analysis of transcription factor binding motifs. M2-promoting effects were mediated specifically through β2-adrenergic receptors and were associated with CREB, C/EBPβ, and ATF transcription factor pathways but not with established M1M2 STAT pathways. Thus, β-adrenergic-signaling induces a macrophage transcriptome that locates on the M2 side of the M1M2 spectrum but likely accomplishes this effect through a signaling pathway that is atypical for M2-spectrum macrophages. PMID:27485040

  3. Gene targeting by the vitamin D response element binding protein reveals a role for vitamin D in osteoblast mTOR signaling. (United States)

    Lisse, Thomas S; Liu, Ting; Irmler, Martin; Beckers, Johannes; Chen, Hong; Adams, John S; Hewison, Martin


    Transcriptional regulation by hormonal 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] involves occupancy of vitamin D response elements (VDREs) by the VDRE binding protein (VDRE-BP) or 1,25(OH)(2)D(3)-bound vitamin D receptor (VDR). This relationship is disrupted by elevated VDRE-BP, causing a form of hereditary vitamin D-resistant rickets (HVDRR). DNA array analysis showed that of 114 genes regulated by 1,25(OH)(2)D(3) in control cells, almost all (113) were rendered insensitive to the hormone in VDRE-BP-overexpressing HVDRR cells. Among these was the gene for DNA-damage-inducible transcript 4 (DDIT4), an inhibitor of mammalian target of rapamycin (mTOR) signaling. Chromatin immunoprecipitation PCR using 1,25(OH)(2)D(3)-treated osteoblasts confirmed that VDR and VDRE-BP compete for binding to the DDIT4 gene promoter. Expression of DDIT4 mRNA in these cells was induced (1.6-6 fold) by 1,25(OH)(2)D(3) (10-100 nM), and Western blot and flow cytometry analysis showed that this response involved suppression of phosphorylated S6K1(T389) (a downstream target of mTOR) similar to rapamycin treatment. siRNA knockdown of DDIT4 completely abrogated antiproliferative responses to 1,25(OH)(2)D(3), whereas overexpression of VDRE-BP exerted a dominant-negative effect on transcription of 1,25(OH)(2)D(3)-target genes. DDIT4, an inhibitor of mTOR signaling, is a direct target for 1,25(OH)(2)D(3) and VDRE-BP, and functions to suppress cell proliferation in response to vitamin D.

  4. Suppression of iron-regulatory hepcidin by vitamin D. (United States)

    Bacchetta, Justine; Zaritsky, Joshua J; Sea, Jessica L; Chun, Rene F; Lisse, Thomas S; Zavala, Kathryn; Nayak, Anjali; Wesseling-Perry, Katherine; Westerman, Mark; Hollis, Bruce W; Salusky, Isidro B; Hewison, Martin


    The antibacterial protein hepcidin regulates the absorption, tissue distribution, and extracellular concentration of iron by suppressing ferroportin-mediated export of cellular iron. In CKD, elevated hepcidin and vitamin D deficiency are associated with anemia. Therefore, we explored a possible role for vitamin D in iron homeostasis. Treatment of cultured hepatocytes or monocytes with prohormone 25-hydroxyvitamin D or active 1,25-dihydroxyvitamin D decreased expression of hepcidin mRNA by 0.5-fold, contrasting the stimulatory effect of 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D on related antibacterial proteins such as cathelicidin. Promoter-reporter and chromatin immunoprecipitation analyses indicated that direct transcriptional suppression of hepcidin gene (HAMP) expression mediated by 1,25-dihydroxyvitamin D binding to the vitamin D receptor caused the decrease in hepcidin mRNA levels. Suppression of HAMP expression was associated with a concomitant increase in expression of the cellular target for hepcidin, ferroportin protein, and decreased expression of the intracellular iron marker ferritin. In a pilot study with healthy volunteers, supplementation with a single oral dose of vitamin D (100,000 IU vitamin D2) increased serum levels of 25D-hydroxyvitamin D from 27±2 ng/ml before supplementation to 44±3 ng/ml after supplementation (P<0.001). This response was associated with a 34% decrease in circulating levels of hepcidin within 24 hours of vitamin D supplementation (P<0.05). These data show that vitamin D is a potent regulator of the hepcidin-ferroportin axis in humans and highlight a potential new strategy for the management of anemia in patients with low vitamin D and/or CKD.

  5. Unusual electronic features and reactivity of the dipyridylazaallyl ligand: characterizations of (smif)2M [M = Fe, Co, Co+, Ni; smif = {(2-py)CH}2N] and [(TMS)2NFe]2(smif)2. (United States)

    Frazier, Brenda A; Wolczanski, Peter T; Lobkovsky, Emil B; Cundari, Thomas R


    Application of the dipyridylazaallyl ligand (2-py)CHNCH(2-py) (smif) to a series of first-row transition metals afforded (smif)(2)M(n) [n = 0, M = Fe (1), Co (2), Ni (3); n = +1, M = Co (2+)] and {(TMS)(2)NFe}(2)(smif)(2) (4(2)) via metathetical procedures. The Mossbauer spectrum of 1 (S = 0) and TDDFT calculations, including a UV-vis spectral simulation, reveal it to be a covalent, strong-field system with Delta(o) estimated as approximately 18,000 cm(-1) and B approximately 470 cm(-1). (smif)(2)Co (2) has S = 1/2 according to SQUID data at 10 K. DFT calculations suggest that the odd electron is localized in a smif pi* orbital, i.e., smif is redox-active. EPR-silent (smif)(2)Ni (3) has S = 1 (SQUID), and calculations show that the unpaired spins reside in the d(z(2)) and d(x(2))(-y(2)) orbitals. X-ray structural parameters suggest that low-spin d(6) 1 and 2+ are relatively symmetric D(2d) species, but 2 and 3 manifest a distortion in which one smif is canted in the plane perpendicular to the other. (smif)FeN(TMS)(2) (4) is principally monomeric in solution, but reversibly dimerizes (K(eq) approximately 10(-4) M(-1)) via C-C bond formation in the azaallyl backbone to crystallize as {(TMS)(2)NFe}(2)(smif)(2) (4(2)). The azaallyl compounds possess extraordinary UV-vis absorptivities (epsilon approximately 18,000-52,000) at 580 +/- 15 nm and 406(25) nm that have been identified as intraligand bands with C(nb) --> smif pi* character.

  6. Clinical applications of HPLC-competitive protein binding assay for serum 25-hydroxyvitamin D

    Energy Technology Data Exchange (ETDEWEB)

    Shouli, Yang [China-Japan Friendship Hospital, Beijing, BJ (China). Inst. of Clinical Medical Science; and others


    This report describes the clinical applications of HPLC-competitive protein binding assay for serum 25(OH) Vit D in 156 cases. Serum 25(OH) Vit D of normal human was 33.1 +- 14.8 nmol/L (13.2 +- 5.9 ng/ml), while for various diseases are as follows: rickets, 18.0 +- 9.0 nmol/L (7.2 +- 3.6 ng/ml, n = 36, P < 0.005); hypervitaminosis D, 116.8 +- 31.3 nmol/L (46.7 +- 12.3 ng/ml, n = 6, P < 0.001); renal diseases of children, 25.3 +- 7.3 nmol/L (10.1 +- 2.9 ng/ml, n = 9. P > 0.1); pneumonia of children, 33.8 +- 14.8 nmol/L (13.5 +- 5.9 ng/ml, n = 10, P > 0.5); cirrhosis, 13.8 +- 11.3 nmol/L (5.5 +- 4.5 ng/ml, n = 9, P < 0.001); vasculitis, 25.5 +- 15.3 nmol/L (10.2 +- 6.1 ng/ml, n = 5, P > 0.2); administration of anticonvulsant (1 to 15 years), 19.0 +- 6.5 nmol/L (7.6 +- 2.6 ng/ml, n = 19, P < 0.001); administration of glococorticoids (> 6 months), 15.3 +- 5.0 nmol/L (6.1 +- 2.0 ng/ml, n = 6, P < 0.005); hyperthyroidism, 34.0 +- 23.5 nmol/L (13.6 +- 9.4 ng/ml, n = 13, P > 0.5); pregnant women, 39.8 +- 16.5 nmol/L (15.9 +- 6.6 ng/ml, n = 7, P > 0.1). We found it is a useful reference value for most of the above diseased state especially for differentiation between rickets and hypervitaminosis.

  7. Dopamine D2 receptor occupancy in normal humans treated with a novel antipsychotic drug YKP1358 measured by PET and [11c]raclopride

    International Nuclear Information System (INIS)

    Lee, J. S.; Kim, S. J.; Lee, K. J.; Kim, E.; Yu, K. S.; Jang, I. J.; Kwon, J. S.; Kang, W. J.; Jeong, J. M.; Lee, D. S.; Chung, J. K.; Lee, M. C.


    YKP1358 is a novel serotonin (5-HT 2A ) and dopamine (D 2 ) antagonist, and fitted the general profile of an atypical neuroleptic agent in preclinical studies. The time course of D 2 receptor occupancy in the brain of living human after a single oral dose of YKP1358 was measured using PET and related to the plasma drug levels. A single oral dose, dose escalation (100 mg, 200 mg, and 250 mg), open-label study was performed in 9 healthy male volunteers (3 per each dose) using the [ 11 C]raclopried PET. After the baseline scan, each subject was studied at 2, 5, and 10 hours after the single administration of YKP1358. Blood samples for evaluation of plasma concentration of YKP1358 were also taken at various time points (0-32 hours post-dose). Binding potential (BP) of [ 11 C]raclopride in the putamen was estimated with simplified reference tissue model and percent reduction of the BP was calculated to obtain the D 2 receptor occupancy. BP parametric image was generated using a pixel-wise Logan noninvasive plot. T max of plasma concentration-time profiles was 0.67 hours, and elimination half-life was 5.71, 7.46, and 8.58 hours in 100 mg, 200 mg, and 250 mg dosing groups, respectively. D 2 receptor occupancy of YKP1358 was 60 to 80% at 2 hours, 40 to 60% at 5 hours, and 20 to 50% at 10 hours. The relationship of plasma concentration and D 2 receptor occupancy of YKP1358 was well predicted by Emax model, and Emax was 100 %, EC50 was 8.9 (=1.1) ng/mI, and Hills coefficient was 0.525. PK profile of YKP1358 showed individual variation, but the D 2 receptor occupancy was less variable and well predicted by an Emax model. Since D 2 antagonists show therapeutic effects at 50 to 80% D 2 occupancy and the EC50 of YKP1358 is less than 10 ng/ml, doses of YKP1358 which maintain plasma concentrations above 10 ng/ml are expected to show therapeutic effects

  8. Vitamin D deficiency in early pregnancy.

    Directory of Open Access Journals (Sweden)

    Shannon K Flood-Nichols

    Full Text Available Vitamin D deficiency is a common problem in reproductive-aged women in the United States. The effect of vitamin D deficiency in pregnancy is unknown, but has been associated with adverse pregnancy outcomes. The objective of this study was to analyze the relationship between vitamin D deficiency in the first trimester and subsequent clinical outcomes.This is a retrospective cohort study. Plasma was collected in the first trimester from 310 nulliparous women with singleton gestations without significant medical problems. Competitive enzymatic vitamin D assays were performed on banked plasma specimens and pregnancy outcomes were collected after delivery. Logistic regression was performed on patients stratified by plasma vitamin D concentration and the following combined clinical outcomes: preeclampsia, preterm delivery, intrauterine growth restriction, gestational diabetes, and spontaneous abortion.Vitamin D concentrations were obtained from 235 patients (mean age 24.3 years, range 18-40 years. Seventy percent of our study population was vitamin D insufficient with a serum concentration less than 30 ng/mL (mean serum concentration 27.6 ng/mL, range 13-71.6 ng/mL. Logistic regression was performed adjusting for age, race, body mass index, tobacco use, and time of year. Adverse pregnancy outcomes included preeclampsia, growth restriction, preterm delivery, gestational diabetes, and spontaneous abortion. There was no association between vitamin D deficiency and composite adverse pregnancy outcomes with an adjusted odds ratio of 1.01 (p value 0.738, 95% confidence intervals 0.961-1.057.Vitamin D deficiency did not associate with adverse pregnancy outcomes in this study population. However, the high percentage of affected individuals highlights the prevalence of vitamin D deficiency in young, reproductive-aged women.

  9. Elastin-derived peptides promote abdominal aortic aneurysm formation by modulating M1/M2 macrophage polarization1 (United States)

    Dale, Matthew A; Xiong, Wanfen; Carson, Jeffrey S; Suh, Melissa K; Karpisek, Andrew D.; Meisinger, Trevor M.; Casale, George P.; Baxter, B. Timothy


    Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Damage to elastin in the ECM results in release of elastin-derived peptides (EDPs), which are chemotactic for inflammatory cells such as monocytes. Their effect on macrophage polarization is less well known. Pro-inflammatory M1 macrophages initially are recruited to sites of injury but, if their effects are prolonged, they can lead to chronic inflammation that prevents normal tissue repair. Conversely, anti-inflammatory M2 macrophages reduce inflammation and aid in wound healing. Thus, a proper M1/M2 ratio is vital for tissue homeostasis. AAA tissue reveals a high M1/M2 ratio where pro-inflammatory cells and their associated markers dominate. In the present study, in vitro treatment of bone marrow-derived macrophages with EDPs induced M1 macrophage polarization. By using C57Bl/6 mice, antibody-mediated neutralization of EDPs reduced aortic dilation, matrix metalloproteinase activity, and pro-inflammatory cytokine expression at early and late time points after aneurysm induction. Furthermore, direct manipulation of the M1/M2 balance altered aortic dilation. Injection of M2 polarized macrophages reduced aortic dilation after aneurysm induction. EDPs promoted a pro-inflammatory environment in aortic tissue by inducing M1 polarization and neutralization of EDPs attenuated aortic dilation. The M1/M2 imbalance is vital to aneurysm formation. PMID:27183603

  10. New coordination polymers from 1D chain, 2D layer to 3D framework constructed from 1,2-phenylenediacetic acid and 1,3-bis(4-pyridyl)propane flexible ligands

    International Nuclear Information System (INIS)

    Xin Lingyun; Liu Guangzhen; Wang Liya


    The hydrothermal reactions of Cd, Zn, or Cu(II) acetate salts with H 2 PHDA and BPP flexible ligands afford three new coordination polymers, including [Cd(PHDA)(BPP)(H 2 O)] n (1), [Zn(PHDA)(BPP)] n (2), and [Cu 2 (PHDA) 2 (BPP)] n (3) (H 2 PHDA=1,2-phenylenediacetic acid, BPP=1,3-bis(4-pyridyl)propane). The single-crystal X-ray diffractions reveal that all three complexes feature various metal carboxylate subunits extended further by the BPP ligands to form a diverse range of structures, displaying a remarked structural sensitivity to metal(II) cation. Complex 1 containing PHDA-bridged binuclear cadmium generates 1D double-stranded chain, complex 2 results in 2D→2D interpenetrated (4,4) grids, and complex 3 displays a 3D self-penetrated framework with 4 8 6 6 8 rob topology. In addition, fluorescent analyses show that both 1 and 2 exhibit intense blue-violet photoluminescence in the solid state. - Graphical Abstract: We show diverse supramolecular frameworks based on the same ligands (PHDA and BPP) and different metal acetate salts including 1D double-stranded chain, 2D2D twofold interpenetrated layer, and 3D self-penetration networks. Highlights: → Three metal(II = 2 /* ROMAN ) coordination polymers were synthesized using H 2 PHDA and BPP. → The diversity of structures show a remarked sensitivity to metal(II) center. → Complexes show the enhancement of fluorescence compared to that of free ligand.


    Directory of Open Access Journals (Sweden)

    Jesse P. Gates


    Full Text Available Jiāng Lì. 2015. A Grammar of Guìqióng: A Language of Sichuan. Leiden: Brill. xiv + 452 pp. ISBN 9789004292093 (hardback 213USD - E-ISBN 9789004293045 (electronic 217USD. Jiang Li's A Grammar of Guìqióng (henceforth, AGG is a revision of her PhD dissertation at the University of Berne under the supervision of George Van Driem. It is a most welcome contribution to our understanding of this under-described language. The primary dialects of Guiqiong described in AGG are spoken in Changma Village of Maibeng Township and Qianxi Village of Qianxi Township, both in Kangding County, Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China. Some praiseworthy aspects of AGG include a plethora of examples sentences; a total of about 1500 example sentences are in the book. Included in the list of abbreviations are the linguistic forms from Guiqiong. The inclusion of photographs of the Guiqiong people and their geographic setting adds interest and appeal to the book. Appendix 1 (321-347 contains six texts of "sayings, stories, and recollections." This review is divided into sections similar to the divisions that the chapters of AGG provide: Introduction to AGG, Phonology, Morphology, Syntax, Errata, and Conclusion. Comments on AGG's chapter on pragmatics will be incorporated into the section on syntax since AGG's chapter on pragmatics is very short. Back-matter will also be briefly overviewed in the syntax section. ...

  12. Modulation by calcineurin of 5-HT3 receptor function in NG108-15 neuroblastoma x glioma cells

    NARCIS (Netherlands)

    Boddeke, HWGM; Meigel, [No Value; Boeijinga, P; Arbuckle, J; Docherty, RJ

    1 We have investigated the mechanism of regulation of 5-HT3 receptor channel sensitivity in voltage-clamped (-80 mV) NG108-15 neuroblastoma cells. 2 The 5-HT-induced inward current activated rapidly. The fast onset was followed by a biphasic decay which was characterized by two time constants,

  13. Modulation by calcineurin of 5-HT3receptor function in NG108-15 neuroblastoma x glioma cells

    NARCIS (Netherlands)

    Boddeke, H.W.G.M.; Meigel, I.; Boeijinga, P.; Arbuckle, J.; Docherty, R.J.


    1. We have investigated the mechanism of regulation of 5-HT3receptor channel sensitivity in voltage-clamped (-80 mV) NG108-15 neuroblastoma cells. 2. The 5-HT-induced inward current activated rapidly. The fast onset was followed by a biphasic decay which was characterized by two time constants,

  14. Resveratrol regulates microglia M1/M2 polarization via PGC-1α in conditions of neuroinflammatory injury. (United States)

    Yang, Xiaodong; Xu, Shaoqing; Qian, Yiwei; Xiao, Qin


    Microglia are the primary cells that exert immune function in the central nervous system (CNS), and accumulating evidence suggests that microglia act as key players in the initiation of neurodegenerative diseases. It is now well recognized that microglia have functional plasticity and dual phenotypes, proinflammatory M1 and anti-inflammatory M2 phenotypes. Inhibiting the M1 phenotype while stimulating the M2 phenotype has been suggested as a potential therapeutic approach for the treatment of neuroinflammation-related diseases. Resveratrol has been demonstrated to exert anti-inflammatory effects by suppressing M1 microglia activation. However, the role of resveratrol in regulating microglia polarization and the molecular mechanisms involved have not been fully clarified. In this study, we tested whether resveratrol could suppress microglia activation by promoting microglia polarization toward the M2 phenotype via PGC-1α by measuring M1 and M2 markers in vitro and in vivo. Our study demonstrated that resveratrol reduced inflammatory damage and promoted microglia polarization to the M2 phenotype in LPS-induced neuroinflammation. In addition, resveratrol ameliorated LPS-induced sickness behavior in mice. The promoting effects of resveratrol on M2 polarization were attenuated by knocking down PGC-1α. PGC-1α not only suppressed LPS-evoked M1 marker expression by inhibition of NF-κB activity but also increased M2 marker expression by coactivation of the STAT6 and STAT3 pathways. We propose that overexpression PGC-1α by resveratrol could be a potential therapeutic approach to suppress neuroinflammation by regulating microglia polarization. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Supplement to CCM.D-K4 'Hydrometer' report: linkage of EURAMET.M.D-K4 comparison, SIM.M.D-K4 comparison and the supplementary SIM.M.D-S2 to CCM.D-K4 'Hydrometer' (United States)

    Lorefice, S.; Becerra, L. O.


    Evaluation of different types of comparisons to a common set of reference values of a CIPM key comparison is essential to satisfy the concept of the CIPM Mutual Recognition Arrangement (CIPM MRA), where the DoEs of any participant who took part in comparisons should be within the Calibration and Measurement Capability (CMC) section of the CIPM MRA Key Comparison Data Base. The subject of this supplementary report is therefore to present the equivalence of each National Metrological Institute (NMI) participant in the CCM.D-K4 'Hydrometer' key comparison, which was performed in the density range 600 kg/m3 to 2000 kg/m3 at the temperature of 20 °C, and the linkage of the European and Inter-American NMI results performed in the RMO.M.D-K4 comparisons as well as those of the supplementary SIM.M.D-S2 to the common set of KCRVs of the CCM.D-K4 'Hydrometer'. The linking procedure has been obtained by numerical simulation, based on the Monte Carlo method, in which the differences in the results of the different comparison between the intended laboratory and one or more linking laboratory/ies, which took part in both comparisons, are correlated with a continuous function describing the DoEs of the linking laboratory/ies with respect to the common set of KCRVs of the CCM.D-K4. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  16. Vitamin D deficiency and insufficiency among patients with prostate cancer. (United States)

    Trump, Donald L; Chadha, Manpreet K; Sunga, Annette Y; Fakih, Marwan G; Ashraf, Umeer; Silliman, Carrie G; Hollis, Bruce W; Nesline, Mary K; Tian, Lili; Tan, Wei; Johnson, Candace S


    To assess the frequency of vitamin D deficiency among men with prostate cancer, as considerable epidemiological, in vitro, in vivo and clinical data support an association between vitamin D deficiency and prostate cancer outcome. The study included 120 ambulatory men with recurrent prostate cancer and 50 with clinically localized prostate cancer who were evaluated and serum samples assayed for 25-OH vitamin D levels. Then 100 controls (both sexes), matched for age and season of serum sample, were chosen from a prospective serum banking protocol. The relationship between age, body mass index, disease stage, Eastern Cooperative Oncology Group performance status, season and previous therapy on vitamin D status were evaluated using univariate and multivariate analyses. The mean 25-OH vitamin D level was 25.9 ng/mL in those with recurrent disease, 27.5 ng/mL in men with clinically localized prostate cancer and 24.5 ng/mL in controls. The frequency of vitamin D deficiency (<20 ng/mL) and insufficiency (20-31 ng/mL) was 40% and 32% in men with recurrent prostate; 28% had vitamin D levels that were normal (32-100 ng/mL). Among men with localized prostate cancer, 18% were deficient, 50% were insufficient and 32% were normal. Among controls, 31% were deficient, 40% were insufficient and 29% were normal. Metastatic disease (P = 0.005) and season of blood sampling (winter/spring; P = 0.01) were associated with vitamin D deficiency in patients with prostate cancer, while age, race, performance status and body mass index were not. Vitamin D deficiency and insufficiency were common among men with prostate cancer and apparently normal controls in the western New York region.

  17. Effects of Vitamin D Supplementation on Bone Turnover Markers: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Verena Schwetz


    Full Text Available Bone turnover markers (BTMs are used to evaluate bone health together with bone mineral density and fracture assessment. Vitamin D supplementation is widely used to prevent and treat musculoskeletal diseases but existing data on vitamin D effects on markers of bone resorption and formation are inconsistent. We therefore examined the effects of vitamin D supplementation on bone-specific alkaline phosphatase (bALP, osteocalcin (OC, C-terminal telopeptide (CTX, and procollagen type 1 N-terminal propeptide (P1NP. This is a post-hoc analysis of the Styrian Vitamin D Hypertension Trial, a single-center, double-blind, randomized, placebo-controlled trial (RCT performed at the Medical University of Graz, Austria (2011–2014. Two hundred individuals with arterial hypertension and 25-hydroxyvitamin D (25[OH]D levels <75 nmol/L were randomized to 2800 IU of vitamin D daily or placebo for eight weeks. One hundred ninety-seven participants (60.2 ± 11.1 years; 47% women were included in this analysis. Vitamin D had no significant effect on bALP (mean treatment effect (MTE 0.013, 95% CI −0.029 to 0.056 µg/L; p = 0.533, CTX (MTE 0.024, 95% CI −0.163 to 0.210 ng/mL, p = 0.802, OC (MTE 0.020, 95% CI −0.062 to 0.103 ng/mL, p = 0.626, or P1NP (MTE −0.021, 95% CI −0.099 to 0.057 ng/mL, p = 0.597. Analyzing patients with 25(OHD levels <50 nmol/L separately (n = 74 left results largely unchanged. In hypertensive patients with low 25(OHD levels, we observed no significant effect of vitamin D supplementation for eight weeks on BTMs.

  18. Vitamin D nutritional status and antenatal depressive symptoms in African American women. (United States)

    Cassidy-Bushrow, Andrea E; Peters, Rosalind M; Johnson, Dayna A; Li, Jia; Rao, D Sudhaker


    Vitamin D deficiency is associated with depression; however, no studies have examined the relationship of vitamin D and antenatal depression. Antenatal depression increases the risk of adverse birth outcomes and poorer postpartum maternal and infant health. African American women are at increased risk for vitamin D deficiency and antenatal depression. Thus, we examined if early pregnancy vitamin D nutrition (VDN) was associated with antenatal depressive symptoms among African American women in the second trimester of pregnancy. Women (n=178) were recruited from obstetrics clinics of a large health system. VDN was assessed by serum 25-hydroxyvitamin D (25-OHD). Depression symptoms were measured with the Center for Epidemiological Studies Depression (CES-D) scale; CES-D≥16 equates with criteria for clinical depression. Logistic regression was used to examine the association of log-transformed 25-OHD and elevated depression symptoms (CES-D≥16). Mean 25-OHD was 13.4±8.4 ng/mL; most women (82.6%, n=147) were vitamin D inadequate or deficient (25-OHD<20 ng/mL). Mean CES-D was 15.2±10.7, and 74 (41.6%) women had a CES-D≥16, suggestive of clinical depression. A significant inverse relationship was found between log (25-OHD) and CES-D≥16 (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.29-0.99, p=0.046). For every 1-unit increase in log (25-OHD) (corresponding to ~2.72 ng/mL increase in 25-OHD), the odds of CES-D≥16 decreased by 46%. African American women with lower VDN exhibit increased depressive symptoms. Research on vitamin D supplementation for reducing antenatal depressive symptoms is needed.

  19. The organic anion transport polypeptide 1d1 (Oatp1d1) mediates hepatocellular uptake of phalloidin and microcystin into skate liver. (United States)

    Meier-Abt, F; Hammann-Hänni, A; Stieger, B; Ballatori, N; Boyer, J L


    Organic anion transporting polypeptides (rodent Oatp; human OATP) mediate cellular uptake of numerous organic compounds including xenobiotic toxins into mammalian hepatocytes. In the little skate Leucoraja erinacea a liver-specific Oatp (Oatp1d1, also called sOatp) has been identified and suggested to represent an evolutionarily ancient precursor of the mammalian liver OATP1B1 (human), Oatp1b2 (rat), and OATP1B3 (human). The present study tested whether Oatp1d1 shares functional transport activity of the xenobiotic oligopeptide toxins phalloidin and microcystin with the mammalian liver Oatps/OATPs. The phalloidin analogue [(3)H]-demethylphalloin was taken up into skate hepatocytes with high affinity (Km approximately 0.4 microM), and uptake could be inhibited by phalloidin and a variety of typical Oatp/OATP substrates such as bromosulfophthalein, bile salts, estrone-3-sulfate, cyclosporine A and high concentrations of microcystin-LR (Ki approximately 150 microM). When expressed in Xenopus laevis oocytes Oatp1d1 increased uptake of demethylphalloin (Km approximately 2.2 microM) and microcystin-LR (Km approximately 27 microM) 2- to 3-fold over water-injected oocytes, whereas the alternative skate liver organic anion transporter, the dimeric Ostalpha/beta, exhibited no phalloidin and only minor microcystin-LR transport. Also, the closest mammalian Oatp1d1 orthologue, the human brain and testis OATP1C1, did not show any phalloidin transport activity. These results demonstrate that the evolutionarily ancient Oatp1d1 is able to mediate uptake of cyclic oligopeptide toxins into skate liver. The findings support the notion that Oatp1d1 is a precursor of the liver-specific mammalian Oatps/OATPs and that its transport properties are closely associated with certain forms of toxic liver injury such as for example protein phosphatase inhibition by the water-borne toxin microcystin.

  20. The organic anion transport polypeptide 1d1 (Oatp1d1) mediates hepatocellular uptake of phalloidin and microcystin into skate liver

    International Nuclear Information System (INIS)

    Meier-Abt, F.; Hammann-Haenni, A.; Stieger, B.; Ballatori, N.; Boyer, J.L.


    Organic anion transporting polypeptides (rodent Oatp; human OATP) mediate cellular uptake of numerous organic compounds including xenobiotic toxins into mammalian hepatocytes. In the little skate Leucoraja erinacea a liver-specific Oatp (Oatp1d1, also called sOatp) has been identified and suggested to represent an evolutionarily ancient precursor of the mammalian liver OATP1B1 (human), Oatp1b2 (rat), and OATP1B3 (human). The present study tested whether Oatp1d1 shares functional transport activity of the xenobiotic oligopeptide toxins phalloidin and microcystin with the mammalian liver Oatps/OATPs. The phalloidin analogue [ 3 H]-demethylphalloin was taken up into skate hepatocytes with high affinity (Km ∼ 0.4 μM), and uptake could be inhibited by phalloidin and a variety of typical Oatp/OATP substrates such as bromosulfophthalein, bile salts, estrone-3-sulfate, cyclosporine A and high concentrations of microcystin-LR (Ki ∼ 150 μM). When expressed in Xenopus laevis oocytes Oatp1d1 increased uptake of demethylphalloin (Km ∼ 2.2 μM) and microcystin-LR (Km ∼ 27 μM) 2- to 3-fold over water-injected oocytes, whereas the alternative skate liver organic anion transporter, the dimeric Ostα/β, exhibited no phalloidin and only minor microcystin-LR transport. Also, the closest mammalian Oatp1d1 orthologue, the human brain and testis OATP1C1, did not show any phalloidin transport activity. These results demonstrate that the evolutionarily ancient Oatp1d1 is able to mediate uptake of cyclic oligopeptide toxins into skate liver. The findings support the notion that Oatp1d1 is a precursor of the liver-specific mammalian Oatps/OATPs and that its transport properties are closely associated with certain forms of toxic liver injury such as for example protein phosphatase inhibition by the water-borne toxin microcystin

  1. Dopamine D/sub 2/ and D/sub 1/ receptors: biochemical characterization

    Energy Technology Data Exchange (ETDEWEB)

    Niznik, H B


    In order to label dopamine D/sub 2/ receptors reversibly and selectively the potent substituted benzamide neuroleptic, YM-09151-2, was tritium labeled and its binding characteristics to striatal homogenates investigated. (/sup 3/H) YM-09151-2 bound to D/sub 2/ receptors with high affinity in a specific, saturable, reversible and sodium dependent fashion, displaying an appropriate pharmacological D/sub 2/ receptor profile. (/sup 3/H) YM-09151-2 appears to be the ligand of choice for labeling D/sub 2/ receptors since it displays approximately 20-fold lower affinity for serotonergic S/sub 2/ receptors than does (/sup 3/H) spiperone. As an initial step towards the molecular identification of the ligand binding subunit of the striatal D/sub 2/ receptor, photolabile analogues of the substituted benzamide clebopride were synthesized and their reversible and irreversible binding interactions to D/sub 2/ receptors characterized. D/sub 2/ receptor photoinactivation was prevented in a concentration and stereoselective manner by dopaminergic agonists and antagonists. In vivo biodistribution studies with (/sup 125/I) iodoazidoclebopride confirmed the ligand's ability to bind to D/sub 2/ receptor-rich regions and as such, may become a useful tool for the molecular characterization of D/sub 2/ receptor proteins. Digitonin solubilized striatal dopamine D/sub 2/ and D/sub 1/ receptors can be completely separated with full retention of biological activity by steric exclusion High Pressure Liquid Chromatography (HPLC) with corresponding Stokes radii of 7.1 and 5.6 nm.

  2. On D=2 (1/3,1/3) supersymmetric theories 2

    International Nuclear Information System (INIS)

    Saidi, E.H.; Zerouaoui, J.; Sedra, M.B.


    Denoting by D=2 (1/3,1/3) superalgebra; the off critical symmetry of the Φ 5/7,5/7 perturbation of the C=6/7 conformal theory, we build a new superspace solution of the (1/3,1/3) - subalgebra generated by spin ±1/3 charge operators extending the usual (1/2,1/2) supersymmetry generated by spin ±1/2 charges. This solution is based on the use of two Grassmann variables instead of one parafermionic variable θ ±1/3 satisfying the cubic nilpotency condition (θ ±1/3 ) 3 =0. Known results on the C=6/7 tricritical Potts model are recovered as special features. A relation with N=2 Landau-Ginzburg models is also discussed. (author). 17 refs, 1 tab

  3. 1α,25(OH2D3 Induces Actin Depolymerization in Endometrial Carcinoma Cells by Targeting RAC1 and PAK1

    Directory of Open Access Journals (Sweden)

    Ni Zeng


    Full Text Available Background: Cell proliferation and motility require actin reorganization, which is under control of various signalling pathways including ras-related C3 botulinum toxin substrate 1 (RAC1, p21 protein-activated kinase 1 (PAK1 and actin related protein 2 (ARP2. Tumour cell proliferation is modified by 1α,25-Dihydroxy-Vitamin D3 (1α,25(OH2D3, a steroid hormone predominantly known for its role in calcium and phosphorus metabolism. The present study explored whether 1α,25(OH2D3 modifies actin cytoskeleton in Ishikawa cells, a well differentiated endometrial carcinoma cell line. Methods: To this end, actin cytoskeleton was visualized by confocal microscopy. Globular over filamentous actin ratio was determined utilizing Western blotting and flow cytometry, transcript levels by qRT-PCR and protein abundance by immunoblotting. Results: A 24 hour treatment with 1α,25(OH2D3 (100 nM significantly decreased RAC1 and PAK1 transcript levels and activity, decreased ARP2 protein levels and depolymerized actin. The effect of 1α,25(OH2D3 on actin polymerization was mimicked by pharmacological inhibition of RAC1 and PAK1. Conclusions: 1α,25(OH2D3 leads to disruption of RAC1 and PAK1 activity with subsequent actin depolymerization of endometrial carcinoma cells.

  4. Surfactant Protein D Levels in Umbilical Cord Blood and Capillary Blood of Premature Infants

    DEFF Research Database (Denmark)

    Dahl, Marianne; Holmskov, Uffe; Husby, Steffen


    of SP-D in capillary blood day 1 was 1,466 ng/mL (range 410-5,051 ng/mL), with lowest values in infants born with ROM and delivered vaginally. High SP-D levels in umbilical cord blood and capillary blood on day 1 were found to be more likely in infants in need for respiratory support or surfactant...... treatment and susceptibility to infections. We conclude that SP-D concentrations in umbilical cord blood and capillary blood in premature infants are twice as high as in mature infants and depend on several perinatal conditions. High SP-D levels in umbilical cord blood and capillary blood on day 1 were...... found to be related to increased risk of RDS and infections....

  5. Response of Vitamin D Concentration to Vitamin D3 Administration in Older Adults without Sun Exposure: A Randomized Double-Blind Trial. (United States)

    Schwartz, Janice B; Kane, Lynn; Bikle, Daniel


    To determine the dose-response relationship between 25-hydroxyvitamin D (25(OH)D) and supplemental vitamin D3 in elderly nursing home residents. Randomized double-blind investigation. Nursing home. Of 81 women (n=51) and men (n=30) (mean age 87.4±8) enrolled, 72 completed the study. Sixteen weeks of oral vitamin D3 at 800, 2,000, or 4,000 IU/d or 50,000 IU/wk. The main outcome was 25(OH)D concentrations (tandem mass spectrometry) after 16 weeks. Free 25(OH)D and intact parathyroid hormone (iPTH) were also analyzed. Safety monitoring of calcium and estimated glomerular filtration rate was performed, and adherence and clinical status were measured. 25(OH)D concentrations increased with dose (Pd than 800 or 2,000 IU/d, but 800 IU and 2,000 IU/d did not differ. One subject receiving 800 IU/d had concentrations less than 20 ng/mL. All subjects receiving more than 2000 IU/d had concentrations of 20 ng/mL and greater. Free 25(OH)D concentrations rose with total 25(OH) vitamin D. Total and free 25(OH)D were related to calcium concentrations; only free 25(OH)D was related to iPTH. 25(OH)D increased linearly with 800 to 4,000 IU/d and 50,000 IU/wk of vitamin D3, without a ceiling effect. Data suggest that some elderly adults will require more than 800 IU/d of vitamin D3 to ensure adequate vitamin D levels. Changes in 25(OH)D with vitamin D3 were related to starting concentrations (greatest with the lowest concentrations and unchanged with 800 and 2,000 IU/d if 20-40 ng/mL). Relationships between serum calcium and iPTH and free 25(OH)D suggest the potential for free 25(OH)D in defining optimal 25(OH)D concentrations. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  6. Simulated Cholinergic Reinnervation of β (INS-1 Cells: Antidiabetic Utility of Heterotypic Pseudoislets Containing β Cell and Cholinergic Cell

    Directory of Open Access Journals (Sweden)

    Ao Jiao


    Full Text Available Cholinergic neurons can functionally support pancreatic islets in controlling blood sugar levels. However, in islet transplantation, the level of cholinergic reinnervation is significantly lower compared to orthotopic pancreatic islets. This abnormal reinnervation affects the survival and function of islet grafts. In this study, the cholinergic reinnervation of beta cells was simulated by 2D and 3D coculture of INS-1 and NG108-15 cells. In 2D culture conditions, 20 mM glucose induced a 1.24-fold increase (p<0.0001 in insulin secretion from the coculture group, while in the 3D culture condition, a 1.78-fold increase (p<0.0001 in insulin secretion from heterotypic pseudoislet group was observed. Glucose-stimulated insulin secretion (GSIS from 2D INS-1 cells showed minimal changes when compared to 3D structures. E-cadherin expressed in INS-1 and NG108-15 cells was the key adhesion molecule for the formation of heterotypic pseudoislets. NG108-15 cells hardly affected the proliferation of INS-1 cells in vitro. Heterotypic pseudoislet transplantation recipient mice reverted to normoglycemic levels faster and had a greater blood glucose clearance compared to INS-1 pseudoislet recipient mice. In conclusion, cholinergic cells can promote insulin-secreting cells to function better in vitro and in vivo and E-cadherin plays an important role in the formation of heterotypic pseudoislets.

  7. Multiple doses of saw palmetto (Serenoa repens) did not alter cytochrome P450 2D6 and 3A4 activity in normal volunteers. (United States)

    Markowitz, John S; Donovan, Jennifer L; Devane, C Lindsay; Taylor, Robin M; Ruan, Ying; Wang, Jun-Sheng; Chavin, Kenneth D


    Saw palmetto (Serenoa repens) is the most commonly used herbal preparation in the treatment of benign prostatic hyperplasia. The objective of this study was to determine whether a characterized saw palmetto product affects the activity of cytochrome P450 (CYP) 2D6 or 3A4 in healthy volunteers (6 men and 6 women). The probe substrates dextromethorphan (CYP2D6 activity) and alprazolam (CYP3A4 activity) were administered orally at baseline and again after exposure to saw palmetto (320-mg capsule once daily) for 14 days. Dextromethorphan metabolic ratios and alprazolam pharmacokinetics were determined at baseline and after saw palmetto treatment. The mean ratio of dextromethorphan to its metabolite was 0.038 +/- 0.044 at baseline and 0.048 +/- 0.080 after 14 days of saw palmetto administration (P =.704, not significant [NS]), indicating a lack of effect on CYP2D6 activity. The area under the plasma alprazolam concentration versus time curve was 476 +/- 178 h. ng. mL(-1) at baseline and 479 +/- 125 h. ng. mL(-1) after saw palmetto treatment (P =.923, NS), indicating a lack of effect on CYP3A4 activity. The elimination half-life of alprazolam was 11.4 +/- 3.1 hours at baseline and 11.6 +/- 2.7 hours after saw palmetto treatment (P =.770, NS), also indicating a lack of effect on CYP3A4 activity. Our results indicate that extracts of saw palmetto at generally recommended doses are unlikely to alter the disposition of coadministered medications primarily dependent on the CYP2D6 or CYP3A4 pathways for elimination. These conclusions must be weighed in the context of the study's limited assessments and regarded as only the initial investigation into the drug interaction potential of saw palmetto.

  8. Vitamin D and 1,25(OH2D Regulation of T cells

    Directory of Open Access Journals (Sweden)

    Margherita T. Cantorna


    Full Text Available Vitamin D is a direct and indirect regulator of T cells. The mechanisms by which vitamin D directly regulates T cells are reviewed and new primary data on the effects of 1,25 dihydroxyvitamin D (1,25(OH2D on human invariant natural killer (iNKT cells is presented. The in vivo effects of vitamin D on murine T cells include inhibition of T cell proliferation, inhibition of IFN-γ, IL-17 and induction of IL-4. Experiments in mice demonstrate that the effectiveness of 1,25(OH2D requires NKT cells, IL-10, the IL-10R and IL-4. Comparisons of mouse and human T cells show that 1,25(OH2D inhibits IL-17 and IFN-γ, and induces T regulatory cells and IL-4. IL-4 was induced by 1,25(OH2D in mouse and human iNKT cells. Activation for 72h was required for optimal expression of the vitamin D receptor (VDR in human and mouse T and iNKT cells. In addition, T cells are potential autocrine sources of 1,25(OH2D but again only 48–72h after activation. Together the data support the late effects of vitamin D on diseases like inflammatory bowel disease and multiple sclerosis where reducing IL-17 and IFN-γ, while inducing IL-4 and IL-10, would be beneficial.

  9. Comparison of the 1D flux theory with a 2D hydrodynamic secondary settling tank model. (United States)

    Ekama, G A; Marais, P


    The applicability of the 1D idealized flux theory (1DFT) for design of secondary settling tanks (SSTs) is evaluated by comparing its predicted maximum surface overflow (SOR) and solids loading (SLR) rates with that calculated from the 2D hydrodynamic model SettlerCAD using as a basis 35 full scale SST stress tests conducted on different SSTs with diameters from 30 to 45m and 2.25 to 4.1 m side water depth, with and without Stamford baffles. From the simulations, a relatively consistent pattern appeared, i.e. that the 1DFT can be used for design but its predicted maximum SLR needs to be reduced by an appropriate flux rating, the magnitude of which depends mainly on SST depth and hydraulic loading rate (HLR). Simulations of the sloping bottom shallow (1.5-2.5 m SWD) Dutch SSTs tested by STOWa and the Watts et al. SST, all with doubled SWDs, and the Darvill new (4.1 m) and old (2.5 m) SSTs with interchanged depths, were run to confirm the sensitivity of the flux rating to depth and HLR. Simulations with and without a Stamford baffle were also done. While the design of the internal features of the SST, such as baffling, have a marked influence on the effluent SS concentration for underloaded SSTs, these features appeared to have only a small influence on the flux rating, i.e. capacity, of the SST, In the meantime until more information is obtained, it would appear that from the simulations so far that the flux rating of 0.80 of the 1DFT maximum SLR recommended by Ekama and Marais remains a reasonable value to apply in the design of full scale SSTs--for deep SSTs (4 m SWD) the flux rating could be increased to 0.85 and for shallow SSTs (2.5 m SWD) decreased to 0.75. It is recommended that (i) while the apparent interrelationship between SST flux rating and depth suggests some optimization of the volume of the SST, that this be avoided and that (ii) the depth of the SST be designed independently of the surface area as is usually the practice and once selected, the

  10. Frequency measurement of the 2S(1/2)-2D(3/2) electric quadrupole transition in a single 171Yb+ ion. (United States)

    Webster, Stephen; Godun, Rachel; King, Steven; Huang, Guilong; Walton, Barney; Tsatourian, Veronika; Margolis, Helen; Lea, Stephen; Gill, Patrick


    We report on precision laser spectroscopy of the 2S(1/2)(F = 0)-2D(3/2) (F = 2, m(F) = 0) clock transition in a single ion of 171Yb+. The absolute value of the transition frequency, determined using an optical frequency comb referenced to a hydrogen maser, is 688358979309310 +/- 9 Hz. This corresponds to a fractional frequency uncertainty of 1.3 x 10(-14).

  11. Prevalence and correlates of vitamin D status in African American men (United States)

    Tseng, Marilyn; Giri, Veda; Bruner, Deborah W; Giovannucci, Edward


    Background Few studies have examined vitamin D insufficiency in African American men although they are at very high risk. We examined the prevalence and correlates of vitamin D insufficiency among African American men in Philadelphia. Methods Participants in this cross-sectional analysis were 194 African American men in the Philadelphia region who were enrolled in a risk assessment program for prostate cancer from 10/96–10/07. All participants completed diet and health history questionnaires and provided plasma samples, which were assessed for 25-hydroxyvitamin D (25(OH)D) concentrations. We used linear regression models to examine associations with 25(OH)D concentrations and logistic regression to estimate odds ratios (OR) for having 25(OH)D ≥ 15 ng/mL. Results Mean 25(OH)D was 13.7 ng/mL, and 61% of men were classified as having vitamin D insufficiency (25(OH)D 400 vs. 0 IU/day), milk consumption (OR 5.9, 95% CI 2.2, 16.0 for ≥ 3.5 vs. <1 time per week), and blood collection in the summer. Additionally, 25(OH)D concentrations increased with more recreational physical activity (OR 1.3, 95% CI 1.1, 1.6 per hour). A significant inverse association of body mass index with 25(OH)D concentrations in bivariate analyses was attenuated with adjustment for season of blood collection. Conclusion The problem of low vitamin D status in African American men may be more severe than previously reported. Future efforts to increase vitamin D recommendations and intake, such as through supplementation, are warranted to improve vitamin D status in this particularly vulnerable population. PMID:19534831

  12. Potencies of vitamin D analogs, 1α-hydroxyvitamin D3 , 1α-hydroxyvitamin D2 and 25-hydroxyvitamin D3 , in lowering cholesterol in hypercholesterolemic mice in vivo. (United States)

    Quach, Holly P; Dzekic, Tamara; Bukuroshi, Paola; Pang, K Sandy


    Vitamin D 3 and the synthetic vitamin D analogs, 1α-hydroxyvitamin D 3 [1α(OH)D 3 ], 1α-hydroxyvitamin D 2 [1α(OH)D 2 ] and 25-hydroxyvitamin D 3 [25(OH)D 3 ] were appraised for their vitamin D receptor (VDR) associated-potencies as cholesterol lowering agents in mice in vivo. These precursors are activated in vivo: 1α(OH)D 3 and 1α(OH)D 2 are transformed by liver CYP2R1 and CYP27A1 to active VDR ligands, 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] and 1α,25-dihydroxyvitamin D 2 [1,25(OH) 2 D 2 ] , respectively. 1α(OH)D 2 may also be activated by CYP24A1 to 1α,24-dihydroxyvitamin D 2 [1,24(OH) 2 D 2 ], another active VDR ligand. 25(OH)D 3 , the metabolite formed via CYP2R1 and or CYP27A1 in liver from vitamin D 3 , is activated by CYP27B1 in the kidney to 1,25(OH) 2 D 3 . In C57BL/6 mice fed the high fat/high cholesterol Western diet for 3 weeks, vitamin D analogs were administered every other day intraperitoneally during the last week of the diet. The rank order for cholesterol lowering, achieved via mouse liver small heterodimer partner (Shp) inhibition and increased cholesterol 7α-hydroxylase (Cyp7a1) expression, was: 1.75 nmol/kg 1α(OH)D 3  > 1248 nmol/kg 25(OH)D 3 (dose ratio of 0.0014) > > 1625 nmol/kg vitamin D 3 . Except for 1.21 nmol/kg 1α(OH)D 2 that failed to lower liver and plasma cholesterol contents, a significant negative correlation was observed between the liver concentration of 1,25(OH) 2 D 3 formed from the precursors and liver cholesterol levels. The composite results show that vitamin D analogs 1α(OH)D 3 and 25(OH)D 3 exhibit cholesterol lowering properties upon activation to 1,25(OH) 2 D 3 : 1α(OH)D 3 is rapidly activated by liver enzymes and 25(OH)D 3 is slowly activated by renal Cyp27b1 in mouse. Copyright © 2018 John Wiley & Sons, Ltd.

  13. Post treatment PSA nadirs support continuing dose escalation study in patients with pretreatment PSA levels >10 ng/ml, but not in those with PSA <10 NG/ML

    International Nuclear Information System (INIS)

    Herold, D.H.; Hanlon, A.L.; Movsas, B.; Hanks, G.E.


    Purpose: We have recently shown that ICRU reporting point radiation doses above 71 Gy are not associated with improved bNED survival in prostate cancer patients with pretreatment PSA level 20 ng/ml we found a strong correlation between dose and nadir values < 1.0 ng/ml (p=.003) as well as for nadir's < 0.5 ng/ml (p=.04). This dose/nadir effect held at several dose levels, but 74 Gy for nadir values < 1.0 ng/ml and 72 Gy for nadir's < 0.5 ng/ml remained the most significant. 32% of these patients achieved a nadir < 1.0ng/ml and 15% < 0.5ng/ml. Conclusions: This analysis provides strong additional support that patients with pretreatment PSA values of < 10 ng/ml do not benefit from dose escalation beyond an ICRU reporting point dose of 71 Gy. For patients with pretreatment PSA's of 10-19.9 ng/ml there is no dose/nadir response evaluated at a nadir of 1.0 ng/ml; however, there is a borderline effect observed at a nadir of 0.5 ng/ml. Patients with pretreatment PSA's of 20 ng/ml or greater clearly benefit from higher doses as evaluated by PSA nadirs of 1.0 ng/ml, and 0.5 ng/ml. These studies support the continued investigation of dose escalation in treating patients with PSA levels over 10 ng/ml, they do not support continued investigation of dose escalation beyond 71 Gy in patients with pretreatment PSA levels < 10 ng/ml. The failure to demonstrate any dose response for the low PSA group and the finding of only a borderline effect for the intermediate PSA group may be influenced by the relatively small number of patients in our series treated to doses < 70 Gy and the fact that none of our patients were treated to doses below 65.98 Gy. The lower limit of acceptible dose has yet to be defined

  14. M2-F1 in flight over lakebed on tow line (United States)


    the M2-F1 airborne to prove it could fly safely and to train pilots before they were towed behind a C-47 aircraft and released. These initial car-tow tests produced enough flight data about the M2-F1 to proceed with flights behind the C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to l20 mph. A small solid landing rocket, referred to as the 'instant L/D rocket,' was installed in the rear base of the M2-F1. This rocket, which could be ignited by the pilot, provided about 250 pounds of thrust for about 10 seconds. The rocket could be used to extend the flight time near landing if needed. More than 400 ground tows and 77 aircraft tow flights were carried out with the M2-F1. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at NASA's Ames and Langley research centers--the M2-F2 and the HL-10, both built by the Northrop Corporation, and the U.S. Air Force's X-24 program, with an X-24A and -B built by Martin. The Lifting Body program also heavily influenced the Space Shuttle program. The M2-F1 program demonstrated the feasibility of the lifting body concept for horizontal landings of atmospheric entry vehicles. It also demonstrated a procurement and management concept for prototype flight test vehicles that produced rapid results at very low cost (approximately $50,000, excluding salaries of government employees assigned to the project).

  15. Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial. (United States)

    Rahme, Maya; Sharara, Sima Lynn; Baddoura, Rafic; Habib, Robert H; Halaby, Georges; Arabi, Asma; Singh, Ravinder J; Kassem, Moustapha; Mahfoud, Ziyad; Hoteit, Maha; Daher, Rose T; Bassil, Darina; El Ferkh, Karim; El-Hajj Fuleihan, Ghada


    The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double-blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 for 1 year. The subjects' mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m 2 , 55% were women, and 222 completed the 12-month follow-up. Mean serum 25 hydroxyvitamin D (25OHD) was 20 ng/mL, and rose to 26 ng/mL in the low-dose arm, and 36 ng/mL in the high-dose arm, at 1 year (p 76 pg/mL showed a trend for higher BMD increments at all skeletal sites, in the high-dose group, that reached significance at the hip. Adverse events were comparable in the two study arms. This controlled trial shows little additional benefit in vitamin D supplementation at a dose exceeding the IOM recommendation of 600 IU/day on BMD and bone markers, in overweight elderly individuals. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  16. Production of the excited charm mesons D1 and D*2 at HERA

    International Nuclear Information System (INIS)

    Abramowicz, H.; Abt, I.; Adamczyk, L.


    The production of the excited charm mesons D 1 (2420) and D * 2 (2460) in ep collisions has been measured with the ZEUS detector at HERA using an integrated luminosity of 373 pb -1 . The masses of the neutral and charged states, the widths of the neutral states, and the helicity parameter of D 1 (2420) 0 were determined and compared with other measurements and with theoretical expectations. The measured helicity parameter of the D 0 1 allows for some mixing of S- and D-waves in its decay to D *± π -+ . The result is also consistent with a pure D-wave decay. Ratios of branching fractions of the two decay modes of the D * 2 (2460) 0 and D * 2 (2460) ± states were measured and compared with previous measurements. The fractions of charm quarks hadronising into D 1 and D * 2 were measured and are consistent with those obtained in e + e - annihilations.

  17. Aerosolization of fungi, (1→3)-β-D glucan, and endotoxin from flood-affected materials collected in New Orleans homes (United States)

    Adhikari, Atin; Jung, Jaehee; Reponen, Tiina; Lewis, Jocelyn Suzanne; DeGrasse, Enjoli C.; Grimsley, L. Faye; Chew, Ginger L.; Grinshpun, Sergey A.


    Standing water and sediments remaining on flood-affected materials were the breeding ground for many microorganisms in flooded homes following Hurricane Katrina. The purpose of this laboratory study was to examine the aerosolization of culturable and total fungi, (1→3)-β-D glucan, and endotoxin from eight flood-affected floor and bedding materials collected in New Orleans homes, following Hurricane Katrina. Aerosolization was examined using the Fungal Spore Source Strength Tester (FSSST) connected to a BioSampler. Dust samples were collected by vacuuming. A two-stage cyclone sampler was used for size-selective analysis of aerosolized glucan and endotoxin. On average, levels of culturable fungi ranged from undetectable (lower limit = 8.3×104) to 2.6×105 CFU/m2; total fungi ranged from 2.07×105 to 1.6×106 spores/m2; (1→3)-β-D glucan and endotoxin were 2.0×103 – 2.9×104 ng/m2 and 7.0×102 – 9.3×104 EU/m2, respectively. The results showed that 5–15 min sampling is sufficient for detecting aerosolizable biocontaminants with the FSSST. Smaller particle size fractions (1.8 μm) fractions, which raises additional exposure concerns. Vacuuming was found to overestimate inhalation exposure risks by a factor of approximately 102 for (1→3)-β-D glucan and by 103 to 104 for endotoxin as detected by the FSSST. The information generated from this study is important with respect to restoration and rejuvenation of the flood-affected areas in New Orleans. We believe the findings will be significant during similar disasters in other regions of the world including major coastal floods from tsunamis. PMID:19201399

  18. Decreased serum betatrophin levels correlate with improved fasting plasma glucose and insulin secretion capacity after Roux-en-Y gastric bypass in obese Chinese patients with type 2 diabetes: a 1-year follow-up. (United States)

    Guo, Kaifeng; Yu, Haoyong; Lu, Junxi; Bao, Yuqian; Chen, Haibing; Jia, Weiping


    There is increasing evidence that serum betatrophin levels, a hormone derived from adipose tissue and liver, are elevated in type 2 diabetes (T2D). To investigate the relationships among betatrophin and metabolic control, insulin resistance, and pancreatic β-cell function in obese Chinese patients with T2D who underwent Roux-en-Y gastric bypass (RYGB). University hospital, China. This 1-year follow-up study included 34 obese individuals with T2D (18 males, 16 females) who underwent RYGB in our hospital. Anthropometric results, glucose levels, lipid profiles, and serum betatrophin levels were determined before and 1 year after RYGB. The serum betatrophin level decreased significantly after RYGB (72.0 ng/mL [33.4-180.9] versus 35.7 ng/mL [14.8-103.3]); Pfasting plasma glucose and negatively correlated with the changes in the 2-hour C-peptide/fasting C-peptide and homeostasis model of assessment of β-cell function (Pfasting plasma glucose (β = .586, Pfasting C-peptide (β = -.309, P = .021). Circulating betatrophin might be involved in the regulation of glucose control and insulin secretion in obese Chinese with T2D soon after RYGB. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  19. Molecular Mapping of D1, D2 and ms5 Revealed Linkage between the Cotyledon Color Locus D2 and the Male-Sterile Locus ms5 in Soybean

    Directory of Open Access Journals (Sweden)

    Alina Ott


    Full Text Available In soybean, genic male sterility can be utilized as a tool to develop hybrid seed. Several male-sterile, female-fertile mutants have been identified in soybean. The male-sterile, female-fertile ms5 mutant was selected after fast neutron irradiation. Male-sterility due to ms5 was associated with the “stay-green” cotyledon color mutation. The cotyledon color trait in soybean is controlled by two loci, D1 and D2. Association between cotyledon color and male-sterility can be instrumental in early phenotypic selection of sterility for hybrid seed production. The use of such selection methods saves time, money, and space, as fewer seeds need to be planted and screened for sterility. The objectives of this study were to compare anther development between male-fertile and male-sterile plants, to investigate the possible linkages among the Ms5, D1 and D2 loci, and to determine if any of the d1 or d2 mutations can be applied in hybrid seed production. The cytological analysis during anther development displayed optically clear, disintegrating microspores and enlarged, engorged pollen in the male-sterile, female-fertile ms5ms5 plants, a common characteristic of male-sterile mutants. The D1 locus was mapped to molecular linkage group (MLG D1a and was flanked by Satt408 and BARCSOYSSR_01_1622. The ms5 and D2 loci were mapped to MLG B1 with a genetic distance ~12.8 cM between them. These results suggest that use of the d2 mutant in the selection of male-sterile line may attenuate the cost hybrid seed production in soybean.

  20. A 0.1-1.4 GHz inductorless low-noise amplifier with 13 dBm IIP3 and 24 dBm IIP2 in 180 nm CMOS (United States)

    Guo, Benqing; Chen, Jun; Chen, Hongpeng; Wang, Xuebing


    An inductorless noise-canceling CMOS low-noise amplifier (LNA) with wideband linearization technique is proposed. The complementary configuration by stacked NMOS/PMOS is employed to compensate second-order nonlinearity of the circuit. The third-order distortion of the auxiliary stage is also mitigated by that of the weak inversion transistors in the main path. The bias and scaling size combined by digital control words are further tuned to obtain enhanced linearity over the desired band. Implemented in a 0.18 μm CMOS process, simulated results show that the proposed LNA provides a voltage gain of 16.1 dB and a NF of 2.8-3.4 dB from 0.1 GHz to 1.4 GHz. The IIP3 and IIP2 of 13-18.9 and 24-40 dBm are obtained, respectively. The circuit core consumes 19 mW from a 1.8 V supply.

  1. MNK Controls mTORC1:Substrate Association through Regulation of TELO2 Binding with mTORC1

    Directory of Open Access Journals (Sweden)

    Michael C. Brown


    Full Text Available The mechanistic target of rapamycin (mTOR integrates numerous stimuli and coordinates the adaptive response of many cellular processes. To accomplish this, mTOR associates with distinct co-factors that determine its signaling output. While many of these co-factors are known, in many cases their function and regulation remain opaque. The MAPK-interacting kinase (MNK contributes to rapamycin resistance in cancer cells. Here, we demonstrate that MNK sustains mTORC1 activity following rapamycin treatment and contributes to mTORC1 signaling following T cell activation and growth stimuli in cancer cells. We determine that MNK engages with mTORC1, promotes mTORC1 association with the phosphatidyl inositol 3′ kinase-related kinase (PIKK stabilizer, TELO2, and facilitates mTORC1:substrate binding. Moreover, our data suggest that DEPTOR, the endogenous inhibitor of mTOR, opposes mTORC1:substrate association by preventing TELO2:mTORC1 binding. Thus, MNK orchestrates counterbalancing forces that regulate mTORC1 enzymatic activity.

  2. Convergence role of transcriptional coactivator p300 and apparent modification on HMCs metabolic memory induced by high glucose

    Directory of Open Access Journals (Sweden)

    Hong SU


    Full Text Available Objective  To investigate the protein expression of transcriptional coactivator p300, acetylated histone H3 (Ac-H3 and Ac-H4 in human renal mesangial cell (HMCs as imitative "metabolic memory" in vitro, and explore the potential role of convergence point of p300. Methods  The HMCs were divided into the following groups: ① High glucose metabolic memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d, high glucose group (HG, 25mmol/L D-glucose×2d, memory groups (M1, M2, M3, 25mmol/L D-glucose×2days + 5.5mmol/L D-glucose×3d, 6d or 9d, persisting normal glucose group (NG, 5.5mmol/L D-glucose×9d. ② Advanced glycation end products memory model: normal glucose group (NG, 5.5mmol/ L D-glucose×2d, NG+AGEs group (AGEs, 5.5mmol/L D-glucose+250µg/ml AGEs×2d; AGEs memory group (AGEs-M, 5.5mmol/L D-glucose + 250µg/ml AGEs×2d + 5.5mmol/L D-glucose×3d; BSA control group (NG+BSA, 5.5mmol/L D-glucose + 250µg/ml BSA×2d. ③ H2O2 was used to simulate oxidative stress memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d, NG+H2O2 group (H2O2, 5.5mmol/L D-glucose +100µmol/L H2O2×30min; H2O2 memory group [(5.5mmol/ L D-glucose + 100µmol/L H2O2×30min + 5.5mmol/L D-glucose×3d]; normal glucose control group (NG3, 5.5mmol/L D-glucose×3d. ④ Transfection with PKCβ2 memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d; high glucose group (HG, 25mmol/L D-glucose×2d; memory group (M, 25mmol/L D-glucose×2d + 5.5mmol/L D-glucose×3d; Ad5-null memory group (HN, 25mmol/L D-glucose + Ad5-null×2d + 5.5mmol/L D-glucose×3d; PKCβ2 memory group (PO, 25mmol/L D-glucose + Ad5-PKCβ2×2d + 5.5mmol/L D-glucose×3d; inhibitor of PKCβ2 memory group (PI, 25mmol/L D-glucose×2d + 10µmol/L CGP53353 + 5.5mmol/L D-glucose×3d. The expression of intracellular reactive oxygen species (ROS was detected by fluorescence microscope and fluorescence microplate reader. The expression levels of p300, Ac-H3, Ac-H4 and PKCβ2 proteins were

  3. Investigation of the C-3-epi-25(OH)D3 of 25-hydroxyvitamin D3 in urban schoolchildren. (United States)

    Berger, Samantha E; Van Rompay, Maria I; Gordon, Catherine M; Goodman, Elizabeth; Eliasziw, Misha; Holick, Michael F; Sacheck, Jennifer M


    The physiological relevance C-3 epimer of 25-hydroxyvitamin D (3-epi-25(OH)D) is not well understood among youth. The objective of this study was to assess whether demographic/physiologic characteristics were associated with 3-epi-25(OH)D 3 concentrations in youth. Associations between 3-epi-25(OH)D 3 and demographics and between 3-epi-25(OH)D 3 , total 25-hydroxyvitamin (25(OH)D) (25(OH)D 2 + 25(OH)D 3 ), total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides were examined in racially/ethnically diverse schoolchildren (n = 682; age, 8-15 years) at Boston-area urban schools. Approximately 50% of participants had detectable 3-epi-25(OH)D 3 (range 0.95-3.95 ng/mL). The percentage of 3-epi-25(OH)D 3 of total 25(OH)D ranged from 2.5% to 17.0% (median 5.5%). Males were 38% more likely than females to have detectable 3-epi-25(OH)D 3 concentrations. Both Asian and black race/ethnicity were associated with lower odds of having detectable 3-epi-25(OH)D 3 compared with non-Hispanic white children (Asian vs. white, odds ratio (OR) 0.28, 95% confidence interval (CI) 0.14-0.53; black vs. white, OR 0.38, 95%CI 0.23-0.63, p 30 ng/mL) 25(OH)D concentration was associated with higher odds of having detectable 3-epi-25(OH)D 3 than having an inadequate (<20 ng/mL) concentration (OR 4.78, 95%CI 3.23-6.94 or OR 14.10, 95%CI 7.10-28.0, respectively). There was no association between 3-epi-25(OH)D 3 and blood lipids. However, when considering 3-epi-25(OH)D 3 as a percentage of total 25(OH)D, total cholesterol was lower in children with percent 3-epi-25(OH)D 3 above the median (mean difference -7.1 mg/dL, p = 0.01). In conclusion, among schoolchildren, sex, race/ethnicity, and total serum 25(OH)D concentration is differentially associated with 3-epi-25(OH)D. The physiological relevance of 3-epi-25(OH)D 3 may be related to the 3-epi-25(OH)D 3 as a percentage of total 25(OH)D and should be considered in future investigations.

  4. Prevalence of 25-hydroxyvitamin D deficiency in healthy personnel from an academic institution of an urban area in Costa Rica

    Directory of Open Access Journals (Sweden)

    Gamboa-Gamboa T


    Full Text Available Tatiana Gamboa-Gamboa,1 Gabriel Abarca-Soto,2 José G Jiménez-Montero3,4 1Department of Research and Nutrition, Universidad de Ciencias Médicas, San José, Costa Rica; 2Department of Research, School of Medicine, Universidad de Ciencias Médicas, San José, Costa Rica; 3Department of Postgraduate Studies, Universidad de Ciencias Médicas, San José, Costa Rica; 4Department of Endocrinology, Hospital CIMA, San José, Costa Rica Objective: The aim of this study was to determine 25-hydroxyvitamin D concentrations in healthy employees of the Universidad de Ciencias Médicas, Costa Rica. Methods: Levels of 25-hydroxyvitamin D, calcium, phosphorus, intact parathyroid hormone (iPTH, and creatinine were measured in 80 people. Solar ultraviolet radiation exposure and 25-hydroxyvitamin D intake were estimated using a previously designed questionnaire. Participants were 52 women aged (mean ± standard deviation 35.8±10.0 years old, body mass index of 27.1±5.9 kg/m2, and 26 men aged 36.4±10.8 years old, body mass index of 27.5±5.0 kg/m2. Results: All participants were normocalcemic, eight females were postmenopausal, three were hypertensive; none had renal, gastrointestinal, or thyroid disease. The level of 25-hydroxyvitamin D was 23.9±7.0 ng/dL and iPTH 40.1±17.5 pg/dL. A level of 25-hydroxyvitamin D $30 ng/dL was seen in 17% of the population. The eight participants with iPTH higher than 67 ng/dL, had 25-hydroxyvitamin D of 18.9±4.8 ng/dL. Two participants who received 25-hydroxyvitamin D and calcium supplements were excluded. Conclusion: The 25-hydroxyvitamin D insufficiency and deficiency found in healthy employees from an academic center in Costa Rica may be due to working long hours in-doors and solar ultraviolet radiation exposure. It is unknown whether secondary hyperparathyroidism seen in nearly 10% of this population, may have long-term effects on bone health. Keywords: vitamin D deficiency, osteoporosis, secondary hyperparathyroidism

  5. (E-1-(2-Aminophenyl-3-(benzo[d][1,3]dioxol-5-ylprop-2-en-1-one

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    Rodrigo Abonia


    Full Text Available The title chalcone (E-1-(2-aminophenyl-3-(benzo[d][1,3]dioxol-5-ylprop-2-en-1-one was obtained in 76% yield from a NaOH catalyzed Claisen–Schmidt condensation reaction between o-aminoacetophenone and piperonal. This product will be used as a key precursor for the development of an alternative route for the total synthesis of the alkaloid Graveoline. Single crystals of the title compound suitable for X-ray diffraction were grown via slow evaporation in ethanol at room temperature. A complete crystallographic study was performed in depth to unequivocally confirm its structure. The crystal structure of the title o-aminochalcone, C16H13NO3, shows two molecules per asymmetric unit (Z = 4 and adopts an E configuration about the C=C double bond. In the title compound, the mean plane of the non-H atoms of the central chalcone fragment C—C(O—C—C—C is as follow: [root-mean-square (r.m.s. deviation = 0.0210 Å for A–B and 0.0493 for C–D molecules]. In the crystal, molecules are linked by N–H...O and C–H...O, hydrogen bonds forming S(6, R22(6 and edge-fused R44(24rings along with C(18 chains running parallel to (110.

  6. Production of the excited charm mesons D1 and D*2 at HERA

    International Nuclear Information System (INIS)

    Verbytskyi, Andrii


    The production of the excited charm mesons D 1 , D * 2 and D + s1 in ep collisions has been measured with the ZEUS detector at Hera. The data sample taken by the ZEUS detector in the years 2003-2007, corresponding to an integrated luminosity of 373 pb -1 has been used. The masses of the neutral, charged and strange states, the widths of the neutral states, the helicity parameters of D 0 1 and D + s1 were determined and compared with other measurements and with theoretical expectations. The measured helicity parameters of the D 0 1 and D + s1 allows for some mixing of S- and D-waves in their decays to D *± π -+ and D *± K 0 respectively. The measured value of the D 0 1 helicity parameter is also consistent with a pure D-wave decay. Ratios of branching fractions of the two decay modes of the D *0 2 , D2 and D + s1 states were measured and compared with previous measurements. The fractions of charm quarks hadronising into D 1 , D * 2 and D + s1 were measured and are consistent with those obtained in e + e - annihilations. The Grid computing technology has a high importance for modern High Energy Physics. This technology has been successfully used in Zeus experiment for the MC simulations and data analysis. The dedicated infrastructure has been maintained by the author since 2010. In addition to continuous support, the author has upgraded and improved the performance of the Grid MC simulations and contributed to the Zeus data preservation project.

  7. Electric conductivity of double fluorides in the systems M1F-Th(U)F4(M1=K, Tl) and M2F2-ThF4(M2=Ca, Sr, Ba)

    International Nuclear Information System (INIS)

    Murin, I.V.; Andreev, A.M.; Amelin, Yu.V.


    The temperature dependence of electric conductivity of some double fluorides formed in the systems M 1 F-Th(U)F 4 (M 1 =K, Tl) and M 2 F 2 -ThF 4 (M 2 =Ca, Sr, Ba) as well as UF 3 in a wide temperature range is studied. It is shown that the values of electric conductivity and activation energy of these fluorides depend on the compound structure and cation nature. The temperature electric conductivity dependence for double fluorides with the tysonite structure is close to the lanthanum fluoride dependence. Taking into account low electron electric conductivity component the conclusion is drawn that the investigated compounds can be used as solid electrolytes

  8. Cyanide bridged hetero-metallic polymeric complexes: Syntheses, vibrational spectra, thermal analyses and crystal structures of complexes [M(1,2-dmi)2Ni(μ-CN)4]n (M = Zn(II) and Cd(II)) (United States)

    Kürkçüoğlu, Güneş Süheyla; Sayın, Elvan; Şahin, Onur


    Two cyanide bridged hetero-metallic complexes of general formula, [M(1,2-dmi)2Ni(μ-CN)4]n (1,2-dmi = 1,2-dimethylimidazole and M = Zn(II) or Cd(II)) have been synthesized and characterized by vibrational (FT-IR and Raman) spectroscopy, single crystal X-ray diffraction, thermal analyses and elemental analyses. The crystallographic analyses reveal that the complexes, [Zn(1,2-dmi)2Ni(μ-CN)4] (1) and [Cd(1,2-dmi)2Ni(μ-CN)4] (2), have polymeric 2D networks. In the complexes, four cyanide groups of [Ni(CN)4]2- coordinated to the adjacent M(II) ions and distorted octahedral geometries of complexes are completed by two nitrogen atoms of trans 1,2-dmi ligands. The structures of 1 and 2 are similar and linked via intermolecular hydrogen bonding, C-H⋯Ni interactions to give rise to 3D networks. Vibration assignments are given for all the observed bands and the spectral features also supported to the crystal structures of heteronuclear complexes. The FT-IR and Raman spectra of the complexes are very much consistent with the structural data presented.

  9. E2F1 regulates cellular growth by mTORC1 signaling.

    Directory of Open Access Journals (Sweden)

    Sebastian Real


    Full Text Available During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression program is required in this process. Unlike E2F1, E2F3 is unable to activate mTORC1, suggesting that growth activity could be restricted to individual E2F members. The effect of E2F1 on the activation of mTORC1 does not depend on Akt. Furthermore, over-expression of TSC2 does not interfere with the effect of E2F1, indicating that the E2F1-induced signal pathway can compensate for the inhibitory effect of TSC2 on Rheb. Immunolocalization studies demonstrate that E2F1 induces the translocation of mTORC1 to the late endosome vesicles, in a mechanism dependent of leucine. E2F1 and leucine, or insulin, together affect the activation of S6K stronger than alone suggesting that they are complementary in activating the signal pathway. From these studies, E2F1 emerges as a key protein that integrates cell division and growth, both of which are essential for cell proliferation.

  10. M2-F1 in flight during low-speed car tow (United States)


    seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly safely and to train pilots before they were towed behind a C-47 aircraft and released. These initial car-tow tests produced enough flight data about the M2-F1 to proceed with flights behind the C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to l20 mph. A small solid landing rocket, referred to as the 'instant L/D rocket,' was installed in the rear base of the M2-F1. This rocket, which could be ignited by the pilot, provided about 250 pounds of thrust for about 10 seconds. The rocket could be used to extend the flight time near landing if needed. More than 400 ground tows and 77 aircraft tow flights were carried out with the M2-F1. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at NASA's Ames and Langley research centers--the M2-F2 and the HL-10, both built by the Northrop Corporation, and the U.S. Air Force's X-24 program, with an X-24A and -B built by Martin. The Lifting Body program also heavily influenced the Space Shuttle program. The M2-F1 program demonstrated the feasibility of the lifting body concept for horizontal landings of atmospheric entry vehicles. It also demonstrated a procurement and management concept for prototype flight test vehicles that produced rapid results at very low cost (approximately $50,000, excluding salaries of government employees assigned to the project).

  11. MERRA 2D IAU Diagnostic, Surface Fluxes, Monthly Mean (2/3x1/2L1) V5.2.0 (United States)

    National Aeronautics and Space Administration — The MATMNXFLX or tavgM_2d_flx_Nx data product is the MERRA Data Assimilation System 2-Dimensional surface turbulence flux diagnostic that is time averaged...

  12. Low-Intensity Pulsed Ultrasound Enhances Nerve Growth Factor-Induced Neurite Outgrowth through Mechanotransduction-Mediated ERK1/2-CREB-Trx-1 Signaling. (United States)

    Zhao, Lu; Feng, Yi; Hu, Hong; Shi, Aiwei; Zhang, Lei; Wan, Mingxi


    Enhancing the action of nerve growth factor (NGF) is a potential therapeutic approach to neural regeneration. To facilitate neural regeneration, we investigated whether combining low-intensity pulsed ultrasound (LIPUS) and NGF could promote neurite outgrowth, an essential process in neural regeneration. In the present study, PC12 cells were subjected to a combination of LIPUS (1 MHz, 30 or 50 mW/cm 2 , 20% duty cycle and 100-Hz pulse repetition frequency, 10 min every other day) and NGF (50 ng/mL) treatment, and then neurite outgrowth was compared. Our findings indicated that the combined treatment with LIPUS (50 mW/cm 2 ) and NGF (50 ng/mL) promotes neurite outgrowth that is comparable to that achieved by NGF (100 ng/mL) treatment alone. LIPUS significantly increased NGF-induced neurite length, but not neurite branching. These effects were attributed to the enhancing effects of LIPUS on NGF-induced phosphorylation of ERK1/2 and CREB and the expression of thioredoxin (Trx-1). Furthermore, blockage of stretch-activated ion channels with Gd 3+ suppressed the stimulating effects of LIPUS on NGF-induced neurite outgrowth and the downstream signaling activation. Taken together, our findings suggest that LIPUS enhances NGF-induced neurite outgrowth through mechanotransduction-mediated signaling of the ERK1/2-CREB-Trx-1 pathway. The combination of LIPUS and NGF could potentially be used for the treatment of nerve injury and neurodegenerative diseases. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  13. Mass-fragmentographic determination of 25-hydroxy-vitamin D3 using deuterium labeled internal standard

    International Nuclear Information System (INIS)

    Bjorkhem, I.; Holmberg, I.


    25-[26- 2 H 3 ] Hydroxy-vitamin D 3 has been synthesized according to the following route: 3β-acetoxy-27-nor-cholest-5-en-25-one → 3β-acetoxy-27-nor-cholesta-5,7-dien-25-one → [26- 2 H 3 ] cholesta-5,7-diene-3β,25-diol → 25-[26- 2 H 3 ] hydroxy-vitamin D 3 . A fixed amount of 25-[26- 2 H 3 ] hydroxy-vitamin D 3 , usually 250 ng, is added to a fixed amount of serum, usually 2.5 ml, and the mixture is extracted with a chloroform-methanol mixture. The extract is chromatographed on a Sephadex LH-20 column together with a trace amount of 25-[26- 3 H] hydroxy-vitamin D 3 . The chromatographic fraction corresponding to 25-hydroxy-vitamin D 3 is collected and the amount of unlabeled 25-hydroxy-vitamin D 3 is determined from the ratio between the mass fragmentographic recording of m/e 131 (base peak of unlabeled 25-hydroxy-vitamin D 3 ) and m/e 134 (base peak of 25-[26- 2 H 3 ] hydroxy-vitamin D 3 ). The relative standard deviation of the method was about 5%. The mean value for 25-hydroxy-vitamin D 3 obtained from 23 different serum samples from healthy Swedish men and women was 27 ng/ml with a standard deviation of 10 ng/ml

  14. 1D and 2D urban dam-break flood modelling in Istanbul, Turkey (United States)

    Ozdemir, Hasan; Neal, Jeffrey; Bates, Paul; Döker, Fatih


    Urban flood events are increasing in frequency and severity as a consequence of several factors such as reduced infiltration capacities due to continued watershed development, increased construction in flood prone areas due to population growth, the possible amplification of rainfall intensity due to climate change, sea level rise which threatens coastal development, and poorly engineered flood control infrastructure (Gallegos et al., 2009). These factors will contribute to increased urban flood risk in the future, and as a result improved modelling of urban flooding according to different causative factor has been identified as a research priority (Gallegos et al., 2009; Ozdemir et al. 2013). The flooding disaster caused by dam failures is always a threat against lives and properties especially in urban environments. Therefore, the prediction of dynamics of dam-break flows plays a vital role in the forecast and evaluation of flooding disasters, and is of long-standing interest for researchers. Flooding occurred on the Ayamama River (Istanbul-Turkey) due to high intensity rainfall and dam-breaching of Ata Pond in 9th September 2009. The settlements, industrial areas and transportation system on the floodplain of the Ayamama River were inundated. Therefore, 32 people were dead and millions of Euros economic loses were occurred. The aim of this study is 1 and 2-Dimensional flood modelling of the Ata Pond breaching using HEC-RAS and LISFLOOD-Roe models and comparison of the model results using the real flood extent. The HEC-RAS model solves the full 1-D Saint Venant equations for unsteady open channel flow whereas LISFLOOD-Roe is the 2-D shallow water model which calculates the flow according to the complete Saint Venant formulation (Villanueva and Wright, 2006; Neal et al., 2011). The model consists a shock capturing Godunov-type scheme based on the Roe Riemann solver (Roe, 1981). 3 m high resolution Digital Surface Model (DSM), natural characteristics of the pond

  15. Angiotensin II type 2 receptor stimulation increases the rate of NG108-15 cell migration via actin depolymerization. (United States)

    Kilian, Peter; Campbell, Shirley; Bilodeau, Lyne; Guimond, Marie-Odile; Roberge, Claude; Gallo-Payet, Nicole; Payet, Marcel Daniel


    Angiotensin II (Ang II) has been reported to induce migration in neuronal cell types. Using time-lapse microscopy, we show here that Ang II induces acceleration in NG108-15 cell migration. This effect was antagonized by PD123319, a selective AT2 receptor antagonist, but not by DUP753, a selective AT1 receptor antagonist, and was mimicked by the specific AT2 receptor agonist CGP42112. This Ang II-induced acceleration was not sensitive to the inhibition of previously described signaling pathways of the AT2 receptor, guanylyl cyclase/cyclic GMP or p42/p44 mapk cascades, but was abolished by pertussis toxin treatment and involved PP2A activation. Immunofluorescence studies indicate that Ang II or CGP42112 decreased the amount of filamentous actin at the leading edge of the cells. This decrease was accompanied by a concomitant increase in globular actin levels. Regulation of actin turnover in actin-based motile systems is known to be mainly under the control of the actin depolymerizing factor and cofilin. Basal migration speed decreased by 77.2% in cofilin-1 small interfering RNA-transfected NG108-15 cells, along with suppression of the effect of Ang II. In addition, the Ang II-induced increase in cell velocity was abrogated in serum-free medium as well as by genistein or okadaic acid treatment in a serum-containing medium. Such results indicate that the AT2 receptor increases the migration speed of NG108-15 cells and involves a tyrosine kinase activity, followed by phosphatase activation, which may be of the PP2A type. Therefore, the present study identifies actin depolymerization and cofilin as new targets of AT2 receptor action, in the context of cellular migration.

  16. Clinical applications of HPLC-competitive protein binding assay for serum 25-hydroxyvitamin D

    International Nuclear Information System (INIS)

    Yang Shouli


    This report describes the clinical applications of HPLC-competitive protein binding assay for serum 25(OH) Vit D in 156 cases. Serum 25(OH) Vit D of normal human was 33.1 +- 14.8 nmol/L (13.2 +- 5.9 ng/ml), while for various diseases are as follows: rickets, 18.0 +- 9.0 nmol/L (7.2 +- 3.6 ng/ml, n = 36, P 0.1); pneumonia of children, 33.8 +- 14.8 nmol/L (13.5 +- 5.9 ng/ml, n = 10, P > 0.5); cirrhosis, 13.8 +- 11.3 nmol/L (5.5 +- 4.5 ng/ml, n = 9, P 0.2); administration of anticonvulsant (1 to 15 years), 19.0 +- 6.5 nmol/L (7.6 +- 2.6 ng/ml, n = 19, P 6 months), 15.3 +- 5.0 nmol/L (6.1 +- 2.0 ng/ml, n = 6, P 0.5); pregnant women, 39.8 +- 16.5 nmol/L (15.9 +- 6.6 ng/ml, n = 7, P > 0.1). We found it is a useful reference value for most of the above diseased state especially for differentiation between rickets and hypervitaminosis

  17. New coordination polymers from 1D chain, 2D layer to 3D framework constructed from 1,2-phenylenediacetic acid and 1,3-bis(4-pyridyl)propane flexible ligands (United States)

    Xin, Ling-Yun; Liu, Guang-Zhen; Wang, Li-Ya


    The hydrothermal reactions of Cd, Zn, or Cu(II) acetate salts with H 2PHDA and BPP flexible ligands afford three new coordination polymers, including [Cd(PHDA)(BPP)(H 2O)] n(1), [Zn(PHDA)(BPP)] n(2), and [Cu 2(PHDA) 2(BPP)] n(3) (H 2PHDA=1,2-phenylenediacetic acid, BPP=1,3-bis(4-pyridyl)propane). The single-crystal X-ray diffractions reveal that all three complexes feature various metal carboxylate subunits extended further by the BPP ligands to form a diverse range of structures, displaying a remarked structural sensitivity to metal(II) cation. Complex 1 containing PHDA-bridged binuclear cadmium generates 1D double-stranded chain, complex 2 results in 2D→2D interpenetrated (4,4) grids, and complex 3 displays a 3D self-penetrated framework with 4 86 68 rob topology. In addition, fluorescent analyses show that both 1 and 2 exhibit intense blue-violet photoluminescence in the solid state.

  18. Expression of aryl hydrocarbon receptor 1 (AHR1), AHR1 nuclear translocator 1 (ARNT1) and CYP1 family monooxygenase mRNAs and their activity in chicken ovarian follicles following in vitro exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). (United States)

    Antos, Piotr A; Błachuta, Małgorzata; Hrabia, Anna; Grzegorzewska, Agnieszka K; Sechman, Andrzej


    The aim of this in vitro study was to determine the effect of TCDD and luteinizing hormone (LH) on mRNA expression of aryl hydrocarbon receptor 1 (AHR1), AHR1 nuclear translocator 1 (ARNT1), and the CYP1 family monooxygenases (CYP1A4, CYP1A5, CYP1B1), and to assess the basal and TCDD-induced activity of these enzymes in chicken ovarian follicles. White (WF) and yellowish (YF) prehierarchical follicles and fragments of the theca (TL) and granulosa (GL) layers of the 3 largest preovulatory follicles (F3-F1) were exposed to TCDD (10nM), ovine LH (oLH; 10ng/mL) or a combination of TCDD (10nM) and oLH (10ng/mL), and increasing doses of TCDD (0.01-100nM). AHR1 and ARNT1 mRNA transcripts were found in all examined follicles. The effect of TCDD and oLH on AHR1 and ARNT1 mRNA expression depended on the maturational state of the follicle. CYP1A4 was predominantly expressed in the GL of the F3-F1 follicles; in comparison with the WF, a higher level of CYP1A5 mRNA was found both in the GL and TL of F3-F1 follicles. Alternatively, the highest level of CYP1B1 mRNA was noticed in the WF follicles. In different developmental stages of the follicle TCDD and oLH induced a different CYP1 isoform. TCDD increased EROD and MROD activities in all the investigated ovarian follicles. In conclusion, AHR1 and ARNT1 mRNA expression indicate that the chicken ovary is a target tissue for dioxin and dioxin-like compounds. The expression of CYP1-family genes and TCDD-inducible EROD and MROD activities in ovarian follicles suggest the possibility of xenobiotic detoxification in the chicken ovary. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. The Prostate Health Index in predicting initial prostate biopsy outcomes in Asian men with prostate-specific antigen levels of 4-10 ng/mL. (United States)

    Ng, C F; Chiu, Peter K F; Lam, N Y; Lam, H C; Lee, Kim W M; Hou, Simon S M


    To investigate the role of the Prostate Health Index (phi) in prostate cancer (PCa) detection in patients with a prostate-specific antigen (PSA) level of 4-10 ng/mL receiving their first prostatic biopsy in an Asian population. This was a retrospective study of archived serum samples from patients enlisted in our tissue bank. Patients over 50 years old, with PSA level of 4-10 ng/mL, a negative digital rectal examination, and received their first prostatic biopsy between April 2008 and April 2013, were recruited. The serum sample collected before biopsy was retrieved for the measurement of various PSA derivatives and the phi value was calculated for each patient. The performance of these parameters in predicting the prostatic biopsy results was assessed. Two hundred and thirty consecutive patients, with 21 (9.13 %) diagnosed with PCa, were recruited for this study. Statistically significant differences between PCa patients and non-PCa patients were found for total PSA, PSA density, [-2]proPSA (p2PSA), free-to-total PSA ratio (%fPSA), p2PSA-to-free PSA ratio (%p2PSA), and phi. The areas under the curve of the receiver operating characteristic curve for total PSA, PSA density, %fPSA, %p2PSA, and phi were 0.547, 0.634, 0.654, 0.768, and 0.781, respectively. The phi was the best predictor of the prostatic biopsies results. At a sensitivity of 90 %, the use of the phi could have avoided unnecessary biopsies in 104 (45.2 %) patients. Use of the phi could improve the accuracy of PCa detection in patients with an elevated PSA level and thus avoid unnecessary prostatic biopsies.

  20. N = (2,0) self-dual non-Abelian tensor multiplet in D = 3 + 3 generates N = (1,1) self-dual systems in D = 2 + 2 (United States)

    Nishino, Hitoshi; Rajpoot, Subhash


    We formulate an N = (2 , 0) system in D = 3 + 3 dimensions consisting of a Yang-Mills (YM)-multiplet (ˆ μ ˆ IA, λˆI), a self-dual non-Abelian tensor multiplet (ˆ μ ˆ ν ˆ IB, χˆI ,φˆI), and an extra vector multiplet (C ˆ μ ˆ IC, ρˆI). We next perform the dimensional reductions of this system into D = 2 + 2, and obtain N = (1 , 1) systems with a self-dual YM-multiplet (AIμ ,λI), a self-dual tensor multiplet (BIμν , χI , φI), and an extra vector multiplet (CIμ , ρI). In D = 2 + 2, we reach two distinct theories: 'Theory-I' and 'Theory-II'. The former has the self-dual field-strength Hμν(+)I of CIμ already presented in our recent paper, while the latter has anti-self-dual field strength Hμν(-)I. As an application, we show that Theory-II actually generates supersymmetric-KdV equations in D = 1 + 1. Our result leads to a new conclusion that the D = 3 + 3 theory with non-Abelian tensor multiplet can be a 'Grand Master Theory' for self-dual multiplet and self-dual YM-multiplet in D = 2 + 2, that in turn has been conjectured to be the 'Master Theory' for all supersymmetric integrable theories in D ≤ 3.

  1. Ho3+/Yb3+ co-doped TeO2-BaF2-Y2O3 glasses for ∼1.2 μm laser applications (United States)

    Wang, Shunbin; Li, Chengzhi; Yao, Chuanfei; Jia, Shijie; Jia, Zhixu; Qin, Guanshi; Qin, Weiping


    Intense ∼1.2 μm fluorescence is observed in Ho3+/Yb3+ co-doped TeO2-BaF2-Y2O3 glasses under 915 nm laser diode excitation. The 1.2 μm emission can be ascribed to the transition 5I6→5I8 of Ho3+. With the introducing of BaF2, the content of OH in the glasses drops markedly, and the 1.2 μm emission intensity increases gradually as increasing the concentration percentage of BaF2. Furthermore, microstructured fibers based on the TeO2-BaF2-Y2O3 glasses are fabricated by using a rod-in-tube method, and a relative positive gain of ∼9.42 dB at 1175.3 nm is obtained in a 5 cm long fiber.

  2. Vite et bien 1 A1/A2 : méthode rapide pour adultes

    CERN Document Server

    Miquel, Claire


    Vite et bien s'adresse à des adultes pressés et impatients de communiquer avec succès en français ! Le vocabulaire est simple et usuel et les thèmes, variés, pour faire face, efficacement, à toutes les situations de la vie quotidienne et professionnelle. Livre + CD audio et corrigés inclus. La méthode rapide Vite et bien 1 permet à la fois d'apprendre le français et de découvrir la réalité de la vie en France, les différences culturelles, le langage de la vie quotidienne, le tout en un temps record. En effet, le premier volume couvre, en vingt unités, les niveaux A1 et A2 du Cadre Européen de référence (CECR). Ainsi, en 100 à 120 heures de cours selon les publics, il sera possible d'acquérir une bonne base de grammaire et de vocabulaire, claire, simple, fonctionnelle, et de se sentir à l'aise dans la communication orale et écrite. L'ouvrage s'adresse aux vrais et et aux faux débutants, constituant donc un outil d'apprentissage et/ou de rafraîchissement des connaissances. Chacune des v...

  3. Design, synthesis, and characterization of 0-D, 1-D, and 2-D Zinc–Adeninate coordination assemblies

    Energy Technology Data Exchange (ETDEWEB)

    An, Ji Hyun [Dept. of Chemistry Education, Seoul National University, Seoul (Korea, Republic of); Geib, Steven J. [Dept. of Chemistry, University of Pittsburgh, Pittsburgh (United States); Kim, Myung Gil [Dept. of Chemistry, Chungang University, Seoul (Korea, Republic of)


    In this study, we demonstrate the synthesis and characterization of zinc– adeninate coordination polymers with 0-D, 1-D, and 2-D structures. We describe methods for controlling the structure of these materials by applying different synthetic conditions and discuss their structural relationships. 0-D, 1-D, and 2-D zinc–adeninate coordination polymers with the same metal–adeninate coordination mode were synthesized and characterized. By controlling the temperature, a material with 0-D macrocycle or 1-D chain coordination polymer was prepared. A replacement of pyridine with bipyridine formed 2-D sheet structure by connecting 1-D chains with each other. They exhibited an interesting relationship between synthetic methods and structures. Further study of metal–adeninate coordination chemistry will render a precise control of the structure in synthesis and will open a new venue to new materials with fascinating properties.

  4. Vitamin D status and biomarkers of inflammation in runners

    Directory of Open Access Journals (Sweden)

    Willis KS


    Full Text Available Kentz S Willis1, Derek T Smith2, Kenneth S Broughton3, D Enette Larson-Meyer2,31Extension, 2Division of Kinesiology and Health, 3Department of Family and Consumer Sciences (Human Nutrition, University of Wyoming, Laramie, WY, USABackground and purpose: The extra-skeletal functions of vitamin D – including its role in inflammatory modulation – are now well recognized but have not yet been investigated in an athletic population. Thus, the purpose of this study was to investigate the relationship between vitamin D status and pro- and anti-inflammatory cytokines (as markers of inflammation and immune system function in endurance athletes.Patients and methods: We analyzed fasting blood samples from 19 healthy, endurance-trained male and female runners (following a standardized diet and exercise regimen for vitamin D status (serum 25-hydroxyvitamin D [25(OHD] and specific plasma cytokine concentrations (tumor necrosis factor alpha [TNF-α], interferon-gamma [IFN-γ], interleukin [IL]-4, and IL-10. Serum/plasma concentrations were log-transformed and simple regression analysis was used to determine significant associations between 25(OHD and cytokine concentrations.Results: Forty-two percent of participants had insufficient vitamin D status [25(OHD < 32 ng/mL], whereas 11% were deficient [25(OHD , 20 ng/mL]. TNF-α and IL-4 were variable, ranging from 2.9 to 36.4 pg/mL and 0 to 252.1 pg/mL, respectively. Concentrations of IFN-γ and IL-10 were minimal, with means of 6.7 ± 7.0 pg/mL and 4.8 ± 5.1 pg/mL, respectively. Regression analysis revealed a significant inverse association between 25(OHD and TNF-α concentrations (R2 = 56.5, P < 0.001 but not between 25(OHD and the remaining cytokines, IFN-γ, IL-4, and IL-10 (P = 0.477, 0.694, and 0.673, respectively.Conclusion: These results call further attention to the epidemic of vitamin D insufficiency, even in outdoor athletes, and support a possible link between decreased vitamin D status and one

  5. Regulation of 1,25-dihydroxyvitamin D, receptors by [3H]-1,25-dihydroxyvitamin D3 in cultured cells (T-47D): evidence for receptor upregulation

    International Nuclear Information System (INIS)

    Reinhardt, T.A.; Horst, R.L.


    The authors examined the effect of 1,25-(OH) 2 D 3 on receptor concentration in cultured cells (T-47D). Two days prior to experiment, cells were fed with RPMI 1640 + 10% serum and 24-32 hours prior to experiment the media was replaced with RPMI 1640 + 25 mM Hepes + 1% serum. [ 3 H]-1,25-(OH) 2 D 3 +/- 100-fold molar excess cold hormone was used to treat the cells. Occupied receptors were measured in freshly prepared cytosols. Total receptors were measured following a 16-hour incubation of cytosols in the presence of 0.6 nM [ 3 H]-1,25-(OH) 2 D 3 +/- 100-fold molar excess of cold hormone at 4 0 C. Treatment of cell cultures for 16-18 hours with 0.5-1.0 nM [ 3 H]-1,25-(OH) 2 D 3 resulted in a 30-40% receptor occupancy by the hormone and a 2- to 3-fold increase in total cell receptor as compared to vehicle-treated controls. Time course studies showed a rapid increase in total receptors up to 16 hours post-treatment in the face of declining receptor occupancy. Actinomycin D blocked the [ 3 H]-1,25-(OH) 2 D 3 -dependent rise in cell receptor. The physiological significance of this receptor upregulation is not known nor is it known whether upregulation results from synthesis of new receptors and/or is the result of the activation of preformed receptors by a inducible activator protein

  6. Association between vitamin D deficiency and anemia in inflammatory bowel disease patients with ileostomy

    Directory of Open Access Journals (Sweden)

    Andre Fialho


    Full Text Available Background: Vitamin D deficiency is commonly seen in patients with inflammatory bowel disease (IBD. Vitamin D deficiency in IBD patients with ileostomy has not been systemically studied. The aim of the study was to assess the frequency and risk factors associated with low 25(OH D3 levels in those patients. Methods: 112 eligible IBD patients with ileostomy were studied. Demographic, clinical, and endoscopic variables were analyzed. Vitamin D levels before and after ileostomy were compared when available. Levels of serum 25(OHD3 <20 ng/mL were classed as being deficient. Results: 112 eligible ileostomy patients were included. The mean vitamin D level was 21.47 ± 1.08 ng/dl. Low levels of vitamin D (<30 ng/dl were present in 92 patients (82%. Vitamin D deficiency (<20 ng/dL was seen in 55 patients (49%. There was no difference between patients with or without vitamin D deficiency regarding demographic variables, medication use and duration of ileostomy. Neo-ileal inflammation on endoscopy was not associated with vitamin D deficiency (p = 0.155. Lower levels of phosphorus (p = 0.020 or hemoglobin (p = 0.019 and shorter duration of IBD (p = 0.047 were found in patients with vitamin D deficiency. In multivariate analysis, lower levels of phosphorus (odds ratio [OR]: 1.83, 95% confidence interval [CI]: 1.16–2.89, p = 0.009 and hemoglobin (OR: 1.32, 95% CI: 1.08–1.60, p = 0.006 remained significantly associated with vitamin D deficiency. Conclusion: Vitamin D deficiency is common in IBD patients with ileostomy and is associated with low hemoglobin levels. Further studies are needed to evaluate vitamin D supplementation as a possible adjuvant in the treatment of anemia of chronic disease in IBD patients. Resumo: Introdução: A deficiência de vitamina D em pacientes com doença inflamatória intestinal submetidos a ileostomia não foi estudada sistematicamente. O objetivo desse estudo foi avaliar a frequência e os fatores de

  7. CYP1A1 m1 and m2 polymorphisms: genetic susceptibility to lung cancer

    Directory of Open Access Journals (Sweden)

    Paula Mota


    Full Text Available Lung cancer is considered an environment-related disease that develops as a consequence of exposure to mutagenic agents, namely those present in tobacco. The CYP1A1 gene codifies the phase I enzyme aryl hydrocarbon hydroxilase (AHH belonging to the cytochrome P450 system that plays a major role in the bio-activation of tobacco procarcinogenes. Two CYP1A1 polymorphisms, m1 (T6235C transition and m2 (A4889G transition, are associated with greater enzymatic activity and have been described as genetic susceptibility factors for lung cancer.The aim of this study was to verify if this association holds true in blood samples of 175 lung cancer patients and 217 non-cancer patients from Portugal's midlands region. The samples were studied by restriction fragment length polymorphism (RFLP assay.The allelic frequencies of the mutant alleles were 0.12 for allele C and 1.14 for allele G in the control population. The results were not statistically different from those alleles in the patient population. There was also no statistically significant difference in genotype distribution in lung cancer patients and controls even when combining high risk genotypes. In our control sample, as in other populations of different ethnic origin, both polymorphisms also seem to be in linkage disequilibrium. We conclude that in this sample of the Portuguese population, CYP1A1 m1 and m2 polymorphisms are too rare to be of clinical relevance, and do not seem to be associated with susceptibility to lung cancer. Resumo: O cancro do pulmão é considerado uma doença relacionada com o meio ambiente, consequência da exposição a agentes mutagénicos, nomeadamente os presentes no fumo do tabaco. O gene CYP1A1 codifica a enzima aril hidrocarboneto hidroxilase (AHH, da fase I, do sistema multienzimático do citocromo P450, que desempenha uma função preponderante na bioactivação dos procarcinogénios do tabaco. Dois polimorfismos do CYP1A1, m1 (transi

  8. Differential S1P Receptor Profiles on M1- and M2-Polarized Macrophages Affect Macrophage Cytokine Production and Migration. (United States)

    Müller, Jan; von Bernstorff, Wolfram; Heidecke, Claus-Dieter; Schulze, Tobias


    Introduction . Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P 1-5 ) in order to influence a broad spectrum of biological processes. This study assesses S1P receptor expression on macrophages before and after M1 and M2 polarization and performs a comparative analysis of S1P signalling in the two activational states of macrophages. Methods . Bone marrow derived macrophages (BMDM) from C57 BL/6 mice were cultured under either M1- or M2-polarizing conditions. S1P-receptor expression was determined by quantitative RT-PCR. Influence of S1P on macrophage activation, migration, phagocytosis, and cytokine secretion was assessed in vitro. Results . All 5 S1P receptor subclasses were expressed in macrophages. Culture under both M1- and M2-polarizing conditions led to significant downregulation of S1P 1 . In contrast, M1-polarized macrophages significantly downregulated S1P 4 . The expression of the remaining three S1P receptors did not change. S1P increased expression of iNOS under M2-polarizing conditions. Furthermore, S1P induced chemotaxis in M1 macrophages and changed cytokine production in M2 macrophages. Phagocytosis was not affected by S1P-signalling. Discussion . The expression of different specific S1P receptor profiles may provide a possibility to selectively influence M1- or M2-polarized macrophages.

  9. Evaluation of intraprostatic metabolism of 1,25-dihydroxyvitamin D(3) (calcitriol) using a microdialysis technique. (United States)

    Konety, Badrinath R; Somogyi, George; Atan, Ali; Muindi, Josephia; Chancellor, Michael B; Getzenberg, Robert H


    1,25-dihydroxyvitamin D(3) (calcitriol) inhibits prostate cancer growth in vitro and in vivo. We used a prostate microdialysis technique to better understand the intraprostatic pharmacokinetics of calcitriol, which in turn would facilitate planning for systemic calcitriol therapy in patients with prostate cancer. Male Sprague-Dawley rats were treated with 5 microg of calcitriol intravenously. Animals were either intact (group 1, n = 6) or castrated (group 2, n = 3). Prostate microdialysis was performed by perfusing Krebs solution through a 5-mm linear probe. Effluents were collected hourly from 0 to 20 hours or until death. Serum was collected at baseline and at the end of the experiment. Serum was also obtained from untreated rats at 0, 1, 2, 3, 4, 6, 8, 12, and 24 hours after intraperitoneal injection of calcitriol. Calcitriol levels were measured by radioimmunoassay. The average baseline intraprostatic level of calcitriol in prostate dialysate in intact rats was 21.1 pg/mL (+/-7.5); it was 88 pg/mL (+/-98.4) after calcitriol administration. In castrated animals, the values were 16.6 pg/mL (+/-5.3) and 25.3 pg/mL (+/-10.7). Two peaks in intraprostatic calcitriol levels were observed after intravenous administration: at less than 6 hours after injection and at more than 13 hours after injection. The mean total calcitriol exposure (area under the concentration versus time curve) in the prostate was 297.6 (+/-159) pg/hr/mL (intact) and 272.7 (+/-123.6) pg/hr/mL (castrated). The baseline serum levels were 0.1 to 1 ng/mL and reached a peak of more than 100 ng/mL within 1 hour of intraperitoneal injection. This technique permits real-time measurement of intraprostatic pharmacokinetics of calcitriol. The ratio of the intraprostatic area under the concentration versus time curve to the serum area under the concentration versus time curve of calcitriol was less than 1:100. Hence, within 24 hours of calcitriol administration, only a fraction (less than 1%) of the serum

  10. One-loop corrections of orders (Zα)6m1/m2 and (Zα)7 to the fine structure of muonium

    International Nuclear Information System (INIS)

    Martynenko, A.P.; Faustov, R.N.


    Corrections of orders (Zα) 6 m 1 /m 2 and (Zα) 7 from one-loop two-photon amplitudes to the energy spectra of hydrogen-like atoms are calculated by expanding the relevant integrand in a Taylor series. A method for averaging the resulting quasipotential in the d-dimensional coordinate representation is formulated. Numerical values are obtained for the corresponding contributions to the fine structure of the muonium, hydrogen, and positronium atoms

  11. Enhancing the Production of D-Mannitol by an Artificial Mutant of Penicillium sp. T2-M10. (United States)

    Duan, Rongting; Li, Hongtao; Li, Hongyu; Tang, Linhuan; Zhou, Hao; Yang, Xueqiong; Yang, Yabin; Ding, Zhongtao


    D-Mannitol belongs to a linear polyol with six-carbon and has indispensable usage in medicine and industry. In order to obtain more efficient D-mannitol producer, this study has screened out a stable mutant Penicillium sp. T2-M10 that was isolated from the initial D-mannitol-produced strain Penicillium sp.T2-8 via UV irradiation as well as nitrosoguanidine (NTG) induction. The mutant had a considerable enhancement in yield of D-mannitol based on optimizing fermentation. The production condition was optimized as the PDB medium with 24 g/L glucose for 9 days. The results showed that the production of D-mannitol from the mutant strain T2-M10 increased 125% in contrast with the parental strain. Meanwhile, the fact that D-mannitol is the main product in the mutant simplified the process of purification. Our finding revealed the potential value of the mutant strain Penicillium sp. T2-M10 to be a D-mannitol-producing strain.

  12. Determination of 1,3-dichloro-2-propanol and 3-chloro-1,2-propandiol in soy sauce by headspace derivatization solid-phase microextraction combined with gas chromatography-mass spectrometry. (United States)

    Lee, Maw-Rong; Chiu, Tzu-Chun; Dou, Jianpeng


    This study proposes a method for identifying 1,3-dichloro-2-propanol and 3-chloro-1,2-propandiol in aqueous matrices by using headspace on-fiber derivatization following solid-phase microextraction combined with gas chromatography-mass spectrometry. The optimized SPME experimental procedures for extracting 1,3-dichloro-2-propanol and 3-chloro-1,2-propandiol in aqueous solutions involved a 85 microm polyacrylate-coated fiber at pH 6, a sodium chloride concentration of 0.36 g mL(-1), extraction at 50 degrees C for 15 min and desorption of analytes at 260 degrees C for 3 min. Headspace derivatization was conducted in a laboratory-made design with N-methyl-N-(trimethylsilyl)-trifluoroacetamide vapor following solid-phase microextraction by using 3 microL N-methyl-N-(trimethylsilyl)-trifluoroacetamide at an oil bath temperature of 230 degrees C for 40 s. This method had good repeatability (R.S.D.s or = 0.9972) for ultrapure water and soy sauce samples that were spiked with two analytes. Detection limits were obtained at the ng mL(-1). The result demonstrated that headspace on-fiber derivatization following solid-phase microextraction was a simple, fast and accurate technique for identifying trace 1,3-dichloro-2-propanol and 3-chloro-1,2-propandiol in soy sauce.

  13. Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone

    Energy Technology Data Exchange (ETDEWEB)

    Paz-Filho, G.J.; Mesa-Junior, C.O.; Boguszewski, C.L.; Carvalho, G.A.; Graf, H. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Endocrinologia e Metabologia; Olandoski, M. [Pontificia Univ. Catolica do Parana, Curitiba, PR (Brazil). Nucleo de Bioestatistica; Woellner, L.C. [Centro de Medicina Nuclear, Curitiba, PR (Brazil); Goedert, C.A. [Centro de Tomografia Computadorizada, Curitiba, PR (Brazil)


    Recombinant human thyroid-stimulating hormone (rhTSH) enhances {sup 131}I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG). Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi {sup 131}I, in patients with MNG. Seventeen patients (15 females, 59.0 {+-} 13.1 years), who had never been submitted to {sup 131}I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi {sup 131}I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 {+-} 64.4 mL. {sup 131}I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean {sup 131}I 24-h uptake increased from 18.1 {+-} 9.7 to 49.6 {+-} 13.4% (P < 0.001), a median 2.6-fold increase (1.2 to 9.2). Peak hormonal levels were 10.86 {+-} 5.44 mU/L for TSH (a median 15.5-fold increase), 1.80 {+-} 0.48 ng/dL for free-T4, 204.61 {+-} 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%), painful thyroiditis (29.4%) and hypothyroidism (52.9%). Thyroid volume was reduced by 34.3 {+-} 14.3% after 6 months (P < 0.001) and by 46.0 {+-} 14.6% after 1 year (P < 0.001). Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of {sup 131}I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects. (author)

  14. Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone

    Directory of Open Access Journals (Sweden)

    G.J. Paz-Filho


    Full Text Available Recombinant human thyroid-stimulating hormone (rhTSH enhances 131I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG. Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi 131I, in patients with MNG. Seventeen patients (15 females, 59.0 ± 13.1 years, who had never been submitted to 131I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi 131I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 ± 64.4 mL. 131I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean 131I 24-h uptake increased from 18.1 ± 9.7 to 49.6 ± 13.4% (P < 0.001, a median 2.6-fold increase (1.2 to 9.2. Peak hormonal levels were 10.86 ± 5.44 mU/L for TSH (a median 15.5-fold increase, 1.80 ± 0.48 ng/dL for free-T4, 204.61 ± 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%, painful thyroiditis (29.4% and hypothyroidism (52.9%. Thyroid volume was reduced by 34.3 ± 14.3% after 6 months (P < 0.001 and by 46.0 ± 14.6% after 1 year (P < 0.001. Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of 131I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects.

  15. M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide

    International Nuclear Information System (INIS)

    Genin, Marie; Clement, Francois; Fattaccioli, Antoine; Raes, Martine; Michiels, Carine


    Tumor associated macrophages (TAMs) are present in high density in solid tumors. TAMs share many characteristics with alternatively activated macrophages, also called M2. They have been shown to favor tumor development and a role in chemoresistance has also been suggested. Here, we investigated the effects of M2 in comparison to M1 macrophages on cancer cell sensitivity to etoposide. We set up a model of macrophage polarization, starting from THP-1 monocytes differentiated into macrophages using PMA (Phorbol 12-myristate 13-acetate). Once differentiated (M0 macrophages), they were incubated with IL-4 and IL-13 in order to obtain M2 polarized macrophages or with IFN-gamma and LPS for classical macrophage activation (M1). To mimic the communication between cancer cells and TAMs, M0, M1 or M2 macrophages and HepG2 or A549 cancer cells were co-cultured during respectively 16 (HepG2) or 24 (A549) hours, before etoposide exposure for 24 (HepG2) or 16 (A549) hours. After the incubation, the impact of etoposide on macrophage polarization was studied and cancer cell apoptosis was assessed by western-blot for cleaved caspase-3 and cleaved PARP-1 protein, caspase activity assay and FACS analysis of Annexin V and PI staining. mRNA and protein expression of M1 and M2 markers confirmed the polarization of THP-1-derived macrophages, which provide a new, easy and well-characterized model of polarized human macrophages. Etoposide-induced cancer cell apoptosis was markedly reduced in the presence of THP-1 M2 macrophages, while apoptosis was increased in cells co-cultured with M1 macrophages. On the other hand, etoposide did not influence M1 or M2 polarization. These results evidence for the first time a clear protective effect of M2 on the contrary to M1 macrophages on etoposide-induced cancer cell apoptosis

  16. Zero-Outage Cellular Downlink with Fixed-Rate D2D Underlay

    DEFF Research Database (Denmark)

    Kiilerich Pratas, Nuno; Popovski, Petar


    . D2D connections can be instrumental in localized aggregation of uplink M2M traffic to a more capable cellular device, before being finally delivered to the Base Station (BS). In this paper we show that a fixed M2M rate is an enabler of efficient Machine-Type D2D underlay operation taking place......, but not the interfering channels from the MTDs to U, we prove that there is a positive downlink rate that can always be decoded by U, leading to zero-outage of the downlink signal. This is a rather surprising consequence of the features of the multiple access channel and the fixed rate RM. We also consider the case...... of a simpler, single-user decoder at U with successive interference cancellation. However, with single-user decoder, a positive zero-outage rate exists only when NM = 1 and is zero when NM > 1. This implies that joint decoding is instrumental in enabling fixed-rate underlay operation....

  17. Dexamethasone, BMP-2, and 1,25-dihydroxyvitamin D enhance a more differentiated osteoblast phenotype

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Henriksen, Z; Sørensen, O H


    . Osteoblast phenotypes were induced by either dexamethasone (Dex) or bone morphogenetic protein-2 (BMP-2). Bone marrow was obtained from biopsies at the posterior iliac spine. Cells were isolated by gradient centrifugation and grown to confluence. Cells were treated with 1 nM 1,25-dihydroxyvitamin D (vitamin...... activity was increased by Dex, but not by BMP-2 treatment. P1NP production was decreased after Dex treatment, while BMP-2 had no effect on P1NP levels. Osteocalcin production was low in cultures not stimulated with vitamin D. Dex or BMP-2 treatment alone did not affect the basic osteocalcin levels......, but in combination with vitamin D, BMP-2 increased the osteocalcin production, while Dex treatment completely suppressed osteocalcin production. Further, PTH-induced cAMP production was greatly enhanced by Dex treatment, whereas BMP-2 did not affect cAMP production. Finally, in vitro mineralization was greatly...

  18. Detection of aflatoxin M1 in raw and commercial pasteurized milk in Urmia, Iran. (United States)

    Tajik, Hossein; Rohani, Seyed Mehdi Razavi; Moradi, Mehran


    During the years 2005 and 2006, samples of raw and of pasteurized milk (72 samples each) were collected randomly from various parts of Urmia city in Iran for the detection of aflatoxin M1. Aflatoxin M1 levels were assessed by Enzyme Linked Immuno Sorbent Assay (ELISA). There was a high incidence of AFM1 (100%), in both raw and pasteurized milk samples. The AFM1 levels in 6.25% of samples were higher than the maximum tolerance limit accepted by European Union (50 ng L(-1)), while the observed mean ofAFM1 was lower than those proposed for European diets. Maximum level ofAFM1 in raw and pasteurized samples were 91.8 and 28.5 ng L(-1), while minimum levels were 4.3 and 5.1 ng L(-1), respectively. The levels ofAFM1 in total samples indicated that feeds for cows in this region were contaminated with AFB1 in such a level that appears to be a serious public health problem at the moment. Therefore, there is a need to limit exposure to aflatoxins by imposing regulatory limits.

  19. Vitamin D status in mothers with pre-eclampsia and their infants: a case-control study from Serbia, a country without a vitamin D fortification policy. (United States)

    Djekic-Ivankovic, Marija; Weiler, Hope; Jones, Glenville; Kaufmann, Martin; Kaludjerovic, Jovana; Aleksic-Velickovic, Vesna; Mandić, Ljuba M; Glibetic, Maria


    The objective of the present study was to determine if vitamin D intake and status are associated with pre-eclampsia in a country without a vitamin D fortification policy. A case-control study of pregnancies with (case) and without (control) pre-eclampsia was conducted from January to April when UVB is minimal. Maternal and cord blood obtained at delivery were measured for plasma 25-hydroxycholecalciferol (25-OH-D3), 3-epimer of 25-OH-D3 (3-epi-25-OH-D3) and 24,25-dihydroxycholecalciferol (24,25-(OH)2D3) by LC-MS/MS and maternal 1,25-dihydroxyvitamin D (1,25-(OH)2D). Differences between groups were tested with ANOVA and Bonferroni post hoc tests (Pcase: 11·2 (sd 5·1); control: 16·1 (sd 5·7) ng/ml; P=0·0006), 25-OH-D3 (case: 10·0 (sd 4·9); control: 14·2 (sd 5·8) ng/ml; P=0·002), 3-epi-25-OH-D3 (case: 0·5 (sd 0·2); control: 0·7 (sd 0·2) ng/ml; P=0·0007) and 1,25-(OH)2D (case: 56·5 (sd 26·6); control: 81·0 (sd 25·7) pg/ml; P=0·018), while 24,25-(OH)2D3 was not different between groups. Infants did not differ in total plasma 25-OH-D, 25-OH-D3, 3-epi-25-OH-D3 and 24,25-(OH)2D3, but the mean proportion of 3-epi-25-OH-D3 was higher in the infant case group (case: 7·9 (sd 1·1); control: 7·0 (sd 1·4) % of total 25-OH-D3; P=0·005). A high prevalence of vitamin D deficiency, as defined by plasma 25-OH-D<12 ng/ml, was observed in 47 % of all mothers and 77 % of all infants. These data underscore the need for prenatal vitamin D supplementation and a food fortification policy in Serbia.

  20. Synthesis, characterization and biodistribution of technetium complexes (99Tc/99mTc) with 2-amino-2-deoxy-D-hexose oximes

    International Nuclear Information System (INIS)

    Steinmetz, H.J.


    In the present work, the synthesis and isolation of isomeric complexes of technetium ( 99 Tc/ 99m Tc) with the 2-amino-2-deoxy-D-hexoses D-glucose aminoxime, D-galactose aminoxime and D-mannose aminoxime, the characterization of the complexes as 99 Tc compounds, and bio-distribution studies on the analogous 99m Tc complexes have been untertaken. As a first step, the free ligands were synthesized and identified using elemental analysis, infra-red and nuclear magnetic resonance spectroscopy and FAB mass spectroscopy. In the bio-distribution studies on the 99m Tc complexes of D-glucose aminoxime and of D-galactose aminoxime in NMRI mice, significant short-term accumulation of 99m Tc activity in heart muscle could be detected, which may be attributed to a biochemical transport mechanism. Uptake in the lungs and the liver was found, but a more significant uptake was observed in the kidneys, where the complexes were rapidly secreted in proportion to their concentration in the blood plasma. (orig./BBR) [de

  1. SmD1 Modulates the miRNA Pathway Independently of Its Pre-mRNA Splicing Function.

    Directory of Open Access Journals (Sweden)

    Xiao-Peng Xiong


    Full Text Available microRNAs (miRNAs are a class of endogenous regulatory RNAs that play a key role in myriad biological processes. Upon transcription, primary miRNA transcripts are sequentially processed by Drosha and Dicer ribonucleases into ~22-24 nt miRNAs. Subsequently, miRNAs are incorporated into the RNA-induced silencing complexes (RISCs that contain Argonaute (AGO family proteins and guide RISC to target RNAs via complementary base pairing, leading to post-transcriptional gene silencing by a combination of translation inhibition and mRNA destabilization. Select pre-mRNA splicing factors have been implicated in small RNA-mediated gene silencing pathways in fission yeast, worms, flies and mammals, but the underlying molecular mechanisms are not well understood. Here, we show that SmD1, a core component of the Drosophila small nuclear ribonucleoprotein particle (snRNP implicated in splicing, is required for miRNA biogenesis and function. SmD1 interacts with both the microprocessor component Pasha and pri-miRNAs, and is indispensable for optimal miRNA biogenesis. Depletion of SmD1 impairs the assembly and function of the miRISC without significantly affecting the expression of major canonical miRNA pathway components. Moreover, SmD1 physically and functionally associates with components of the miRISC, including AGO1 and GW182. Notably, miRNA defects resulting from SmD1 silencing can be uncoupled from defects in pre-mRNA splicing, and the miRNA and splicing machineries are physically and functionally distinct entities. Finally, photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP analysis identifies numerous SmD1-binding events across the transcriptome and reveals direct SmD1-miRNA interactions. Our study suggests that SmD1 plays a direct role in miRNA-mediated gene silencing independently of its pre-mRNA splicing activity and indicates that the dual roles of splicing factors in post-transcriptional gene regulation may be

  2. Deletion of the Intestinal Plasma Membrane Calcium Pump, Isoform 1, Atp2b1, in Mice is Associated with Decreased Bone Mineral Density and Impaired Responsiveness to 1, 25-Dihydroxyvitamin D3 (United States)

    Ryan, Zachary C.; Craig, Theodore A.; Filoteo, Adelaida G.; Westendorf, Jennifer J.; Cartwright, Elizabeth J.; Neyses, Ludwig; Strehler, Emanuel E.; Kumar, Rajiv


    The physiological importance of the intestinal plasma membrane calcium pump, isoform 1, (Pmca1, Atp2b1), in calcium absorption and homeostasis has not been previously demonstrated in vivo. Since global germ-line deletion of the Pmca1 in mice is associated with embryonic lethality, we selectively deleted the Pmca1 in intestinal absorptive cells. Mice with loxP sites flanking exon 2 of the Pmca1 gene (Pmca1fl/fl) were crossed with mice expressing Cre recombinase in the intestine under control of the villin promoter to give mice in which the Pmca1 had been deleted in the intestine (Pmca1EKO mice). Pmca1EKO mice were born at a reduced frequency and were small at the time of birth when compared to wild-type (Wt) litter mates. At two months of age, Pmca1EKO mice fed a 0.81% calcium, 0.34% phosphorus, normal vitamin D diet had reduced whole body bone mineral density (P <0.037), and reduced femoral bone mineral density (P <0.015). There was a trend towards lower serum calcium and higher serum parathyroid hormone (PTH) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) concentrations in Pmca1EKO mice compared to Wt mice but the changes were not statistically significant. The urinary phosphorus/creatinine ratio was increased in Pmca1EKO mice (P <0.004). Following the administration of 200 ng of 1α,25(OH)2D3 intraperitoneally to Wt mice, active intestinal calcium transport increased ∼2-fold, whereas Pmca1EKO mice administered an equal amount of 1α,25(OH)2D3 failed to show an increase in active calcium transport. Deletion of the Pmca1 in the intestine is associated with reduced growth and bone mineralization, and a failure to up-regulate calcium absorption in response to 1α,25(OH)2D3. PMID:26392310

  3. Genome-Wide Association Study of Serum 25-Hydroxyvitamin D in US Women. (United States)

    O'Brien, Katie M; Sandler, Dale P; Shi, Min; Harmon, Quaker E; Taylor, Jack A; Weinberg, Clarice R


    Genetic factors likely influence individuals' concentrations of 25-hydroxyvitamin D [25(OH)D], a biomarker of vitamin D exposure previously linked to reduced risk of several chronic diseases. We conducted a genome-wide association study of serum 25(OH)D (assessed using liquid chromatography-tandem mass spectrometry) and 386,449 single nucleotide polymorphisms (SNPs). Our sample consisted of 1,829 participants randomly selected from the Sister Study, a cohort of women who had a sister with breast cancer but had never had breast cancer themselves. 19,741 SNPs were associated with 25(OH)D ( p < 0.05). We re-assessed these hits in an independent sample of 1,534 participants who later developed breast cancer. After pooling, 32 SNPs had genome-wide significant associations ( p < 5 × 10 -8 ). These were located in or near GC , the vitamin D binding protein, or CYP2R1 , a cytochrome P450 enzyme that hydroxylates vitamin D to form 25(OH)D. The top hit was rs4588, a missense GC polymorphism associated with a 3.5 ng/mL decrease in 25(OH)D per copy of the minor allele (95% confidence interval [CI]: -4.1, -3.0; p = 4.5 × 10 -38 ). The strongest SNP near CYP2R1 was rs12794714, a synonymous variant ( p = 3.8 × 10 -12 ; β = 1.8 ng/mL decrease in 25(OH)D per minor allele [CI: -2.2, -1.3]). Serum 25(OH)D concentrations from samples collected from some participants 3-10 years after baseline (811 cases, 780 non-cases) were also strongly associated with both loci. These findings augment our understanding of genetic influences on 25(OH)D and the possible role of vitamin D binding proteins and cytochrome P450 enzymes in determining measured levels. These results may help to identify individuals genetically predisposed to vitamin D insufficiency.

  4. Internal (m=1, n=1) and (m=2, n=1) resistive modes in the toroidal tokamak with circular cross-section

    International Nuclear Information System (INIS)

    Bussac, M.N.; Pellat, R.; Edery, D.; Soule, J.L.


    A linear analysis is presented of the toroidal coupling between the internal resistive modes (m=1, n=1) and (m=2, n=1) in the tokamak with circular cross-section. The resistive and diamagnetic effects are included in the singular layers where the safety factor q takes respectively the values one and two. By expanding the MHD equations in powers of epsilon, the local inverse of the aspect ratio, a system of two coupled equations is obtained for the harmonic amplitudes. When the shear is finite on q=1 the toroidal coupling is negligible. In the opposite limit, one can explain (a) the experimental behaviour of the (m=1, n=1) mode before the internal disruption, and (b) the simultaneous observation of the modes (m=1, n=1) and (m=2, n=1) before the main disruption. (author)

  5. Circulating SFRP5 levels are elevated in drug-naïve recently diagnosed type 2 diabetic patients as compared with prediabetic subjects and controls. (United States)

    Canivell, Silvia; Rebuffat, Sandra; Ruano, Elena G; Kostov, Belchin; Sisó-Almirall, Antoni; Novials, Anna; Ceriello, Antonio; Gomis, Ramon


    Secreted frizzled-related protein 5 (SFRP5) has been linked to obesity. Results are conflicting regarding its association with type 2 diabetes (T2D) in humans. We aimed to investigate circulating SFRP5 in prediabetes and T2D and its potential association with parameters of insulin resistance and beta-cell function. We studied 70 drug-naïve T2D patients, 70 prediabetic subjects and 70 controls. All subjects were body mass index matched to the T2D patients and overweight or obese. SFRP5, hormones and cytokines levels were measured by ELISA. Serum SFRP5 levels were elevated in T2D patients as compared with prediabetic subjects (median 15.6, interquartile range [9-24.5] ng/mL vs 9.8 [5-14.2] ng/mL, p prediabetic subjects and controls (9.8 [5-14.2] ng/mL vs 10.4 [6.7-16.6] ng/mL, p = 0.472, respectively). After adjusting for potential confounders (age, gender, body mass index, triglycerides, high-density lipoprotein cholesterol and blood pressure), T2D was still associated with higher values of SFRP5 as compared with prediabetes in multinomial logistic regression analysis (fully adjusted odds ratio 3.50, 95% confidence interval 1.40-8.79, p = 0.008). The association was more subtle when comparing T2D with normal glucose tolerance state (fully adjusted odds ratio 2.18, 95% confidence interval 0.91-5.21, p = 0.078). Circulating SFRP5 levels were independently associated with T2D as compared with prediabetes and normal glucose tolerance state. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Vitamin D deficiency is associated with insulin resistance in nondiabetics and reduced insulin production in type 2 diabetics. (United States)

    Esteghamati, A; Aryan, Z; Esteghamati, Ar; Nakhjavani, M


    It is not known whether the association of serum 25-hydroxyvitamin D [25(OH)D] with glycemic measurements of individuals without diabetes is similar to those with diabetes or not. This study is aimed to investigate the association of serum 25(OH)D with glycemic markers of diabetics, nondiabetics, and prediabetics. A case-control study was conducted on age and sex matched 1,195 patients with type 2 DM, 121 prediabetics, and 209 healthy controls. Anthropometric variables, lipid profile, glycemic measurements, and serum 25(OH)D levels were recorded. Serum insulin and C-peptide levels were also measured. All glycemic measurements were compared between diabetics and nondiabetics and prediabetics at different vitamin D status. Patients with DM had lower serum 25(OH)D compared to prediabetics and healthy controls. Endogenous insulin production in response to food intake and in fasting was significantly lower in vitamin D deficient patients with DM compared to those with serum 25(OH)D>40 ng/ml. Diabetic women with serum 25(OH)D40 ng/ml. Healthy individuals with serum 25(OH)D<20 ng/ml had signs of insulin resistance as estimated by significant increase of HOMA-IR, HbA1c, and fasting plasma glucose (FPG). In addition, we found that serum 25(OH)D was inversely associated with insulin resistance. Vitamin D deficiency is associated with insulin resistance in nondiabetics, which is independent of obesity. Furthermore, vitamin D deficiency is associated with reduced insulin production in type 2 diabetics, which was mainly observed in men. Accordingly, a gender disparity also exists in association of serum 25(OH)D with glycemic measurements. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Vitamin D prenatal programming of childhood metabolomics profiles at age 3 y. (United States)

    Blighe, Kevin; Chawes, Bo L; Kelly, Rachel S; Mirzakhani, Hooman; McGeachie, Michael; Litonjua, Augusto A; Weiss, Scott T; Lasky-Su, Jessica A


    Background: Vitamin D deficiency is implicated in a range of common complex diseases that may be prevented by gestational vitamin D repletion. Understanding the metabolic mechanisms related to in utero vitamin D exposure may therefore shed light on complex disease susceptibility. Objective: The goal was to analyze the programming role of in utero vitamin D exposure on children's metabolomics profiles. Design: First, unsupervised clustering was done with plasma metabolomics profiles from a case-control subset of 245 children aged 3 y with and without asthma from the Vitamin D Antenatal Asthma Reduction Trial (VDAART), in which pregnant women were randomly assigned to vitamin D supplementation or placebo. Thereafter, we analyzed the influence of maternal pre- and postsupplement vitamin D concentrations on cluster membership. Finally, we used the metabolites driving the clustering of children to identify the dominant metabolic pathways that were influential in each cluster. Results: We identified 3 clusters of children characterized by 1 ) high concentrations of fatty acids and amines and low maternal postsupplement vitamin D (mean ± SD; 27.5 ± 11.0 ng/mL), 2 ) high concentrations of amines, moderate concentrations of fatty acids, and normal maternal postsupplement vitamin D (34.0 ± 14.1 ng/mL), and 3 ) low concentrations of fatty acids, amines, and normal maternal postsupplement vitamin D (35.2 ± 15.9 ng/mL). Adjusting for sample storage time, maternal age and education, and both child asthma and vitamin D concentration at age 3 y did not modify the association between maternal postsupplement vitamin D and cluster membership ( P = 0.0014). Maternal presupplement vitamin D did not influence cluster membership, whereas the combination of pre- and postsupplement concentrations did ( P = 0.03). Conclusions: Young children can be clustered into distinct biologically meaningful groups by their metabolomics profiles. The clusters differed in concentrations of

  8. Serum 25-Hydroxyvitamin D Concentration Is Independently Inversely Associated with Insulin Resistance in the Healthy, Non-Obese Korean Population

    Directory of Open Access Journals (Sweden)

    So Young Ock


    Full Text Available BackgroundWe evaluated the associations between 25-hydroxyvitamin D (25(OHD concentrations in serum and insulin resistance in the healthy Korean population.MethodsWe conducted this cross-sectional analysis in 1,807 healthy Korean people (628 men and 1,179 women aged 30 to 64 years in the Cardiovascular and Metabolic Disease Etiologic Research Center study. All participants were assessed for 25(OHD, fasting glucose, and insulin levels, and completed a health examination and lifestyle questionnaire according to standard procedures. Insulin resistance was defined as the homeostasis model assessment insulin resistance higher than the 75 percentile.ResultsCompared to those in the highest tertile (≥14.3 ng/mL, the odds ratio (OR for insulin resistance was 1.37 (95% confidence interval [CI], 1.01 to 1.86 for the 1st tertile (<9.7 ng/mL and 1.19 (95% CI, 0.08 to 1.62 for the 2nd tertile (9.7 to 14.3 ng/mL after adjusting for age, gender, waist circumference, alcohol consumption, smoking status, physical exercise, season, and cohort. After stratification of the subjects by adiposity, these associations remained only in non-obese subjects (lowest tertile vs. highest tertile, multivariable OR, 1.64; 95% CI, 1.05 to 2.56.ConclusionSerum 25(OHD has an independent inverse association with insulin resistance in the healthy, non-obese Korean population, even among people with vitamin D insufficiency.

  9. CYP2R1 mutations causing vitamin D-deficiency rickets. (United States)

    Thacher, Tom D; Levine, Michael A


    CYP2R1 is the principal hepatic 25-hydroxylase responsible for the hydroxylation of parent vitamin D to 25-hydroxyvitamin D [25(OH)D]. Serum concentrations of 25(OH)D reflect vitamin D status, because 25(OH)D is the major circulating metabolite of vitamin D. The 1α-hydroxylation of 25(OH)D in the kidney by CYP27B1 generates the fully active vitamin D metabolite, 1,25-dihydroxyvitamin D (1,25(OH) 2 D). The human CYP2R1 gene, located at 11p15.2, has five exons, coding for an enzyme with 501 amino acids. In Cyp2r1-/- knockout mice, serum 25(OH)D levels were reduced by more than 50% compared wild-type mice. Genetic polymorphisms of CYP2R1 account for some of the individual variability of circulating 25(OH)D values in the population. We review the evidence that inactivating mutations in CYP2R1 can lead to a novel form of vitamin D-deficiency rickets resulting from impaired 25-hydroxylation of vitamin D. We sequenced the promoter, exons and intron-exon flanking regions of the CYP2R1 gene in members of 12 Nigerian families with rickets in more than one family member. We found missense mutations (L99P and K242N) in affected members of 2 of 12 families. The L99P mutation had previously been reported as a homozygous defect in an unrelated child of Nigerian origin with rickets. In silico analyses predicted impaired CYP2R1 folding or reduced interaction with substrate vitamin D by L99P and K242N mutations, respectively. In vitro studies of the mutant CYP2R1 proteins in HEK293 cells confirmed normal expression levels but completely absent or markedly reduced 25-hydroxylase activity by the L99P and K242N mutations, respectively. Heterozygous subjects had more moderate biochemical and clinical features of vitamin D deficiency than homozygous subjects. After an oral bolus dose of 50,000 IU of vitamin D 2 or vitamin D 3 , heterozygous subjects had lower increases in serum 25(OH)D than control subjects, and homozygous subjects had minimal increases, supporting a semidominant

  10. Radiative rates for E1, E2, M1, and M2 transitions in the Br-like ions Sr IV, Y V, Zr VI, Nb VII, and Mo VIII

    International Nuclear Information System (INIS)

    Aggarwal, Kanti M.; Keenan, Francis P.


    Energies and lifetimes are reported for the lowest 375 levels of five Br-like ions, namely Sr IV, Y V, Zr VI, Nb VII, and Mo VIII, mostly belonging to the 4s 2 4p 5 , 4s 2 4p 4 4ℓ, 4s4p 6 , 4s 2 4p 4 5ℓ, 4s 2 4p 3 4d 2 , 4s4p 5 4ℓ, and 4s4p 5 5ℓ configurations. Extensive configuration interaction has been included and the general-purpose relativistic atomic structure package (GRASP) has been adopted for the calculations. Additionally, radiative rates are listed among these levels for all E1, E2, M1, and M2 transitions. From a comparison with the measurements, the majority of our energy levels are assessed to be accurate to better than 2%, although discrepancies between theory and experiment for a few are up to 6%. An accuracy assessment of the calculated radiative rates (and lifetimes) is more difficult, because no prior results exist for these ions

  11. Toxoplasma encephalitis in HIV: case report | Ng'walali | East ...

    African Journals Online (AJOL)

    P. M. Ng'walali, K. Kibayashi, M. P. Mbonde, A. M. Makata, J. N. Kitinya, S. Tsunenari. Abstract. (East African Medical Journal: 2001 78(5): 275-276). Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · · AJOL African ...

  12. Effect of vitamin D deficiency in Korean patients with acute respiratory distress syndrome. (United States)

    Park, Sojung; Lee, Min Gi; Hong, Sang-Bum; Lim, Chae-Man; Koh, Younsuck; Huh, Jin Won


    Vitamin D modulates innate and adaptive immune responses, and vitamin D deficiency is associated with increased mortality in hospitalized patients with pneumonia. We evaluated the prevalence of vitamin D deficiency in Korean patients with acute respiratory distress syndrome (ARDS) and its effect on the clinical outcomes of ARDS. We retrospectively analyzed the data of 108 patients who had a measured serum level of 25-hydroxy vitamin D3 (25(OH)D3) at the time of diagnosis with ARDS. The clinical outcomes were evaluated based on 25(OH)D3 levels of 20 ng/mL and stratified by quartiles of 25(OH)D3 levels. The mean age of patients was 59.4 years old; 77 (71.3%) were male. Vitamin D deficiency was found in 103 patients (95.4%). The mean 25(OH)D3 level was 8.3 ± 7.0 ng/mL. Neither in-hospital mortality (40.0% vs. 68.0%) nor 6-month mortality (40.0% vs. 71.8%) significantly differed between groups. There were no significant differences in 25(OH)D3 level between survivors (8.1 ± 7.6 ng/mL) and non-survivors (8.5 ± 6.8 ng/mL, p = 0.765). There were no trends toward a difference in mortality among quartiles of 25(OH)D3 levels. However, 25(OH)D3 levels were inversely related with length of hospital stay and intensive care unit stay among in-hospital survivors. Vitamin D deficiency was prevalent in Korean patients with ARDS. However, levels of vitamin D were not associated with mortality. A large, prospective study is needed to evaluate the effects of vitamin D deficiency on clinical outcomes of ARDS.

  13. Transforming growth factor-beta 1 (TGF-beta1) promotes IL-2 mRNA expression through the up-regulation of NF-kappaB, AP-1 and NF-AT in EL4 cells. (United States)

    Han, S H; Yea, S S; Jeon, Y J; Yang, K H; Kaminski, N E


    Transforming growth factor beta1 (TGF-beta1) has been previously shown to modulate interleukin 2 (IL-2) secretion by activated T-cells. In the present studies, we determined that TGF-beta1 induced IL-2 mRNA expression in the murine T-cell line EL4, in the absence of other stimuli. IL-2 mRNA expression was significantly induced by TGF-beta1 (0.1-1 ng/ml) over a relatively narrow concentration range, which led to the induction of IL-2 secretion. Under identical condition, we examined the effect of TGF-beta1 on the activity of nuclear factor AT (NF-AT), nuclear factor kappaB (NF-kappaB), activator protein-1 (AP-1) and octamer, all of which contribute to the regulation of IL-2 gene expression. Electrophoretic mobility shift assays showed that TGF-beta1 markedly increased NF-AT, NF-kappaB and AP-1 binding to their respective cognate DNA binding sites, whereas octamer binding remained constant, as compared with untreated cells. Employing a reporter gene expression system with p(NF-kappaB)3-CAT, p(NF-AT)3-CAT and p(AP-1)3-CAT, TGF-beta1 treatment of transfected EL4 cells induced a dose-related increase in chloramphenicol acetyltransferase activity that correlated well with the DNA binding profile found in the electrophoretic mobility shift assay studies. These results show that TGF-beta1, in the absence of any additional stimuli, up-regulates the activity of key transcription factors involved in IL-2 gene expression, including NF-AT, NF-kappaB and AP-1, to help promote IL-2 mRNA expression by EL4 cells.

  14. Vitamin D and plain type: a study of male patients with schizophrenia (United States)

    Akbar, N. L.; Effendy, E.; Amin, MM


    Schizophrenia is a heterogeneous disorder in which there is an interaction between genetic and environmental factors. Evidence related to vitamin D deficiency and schizophrenia is aresidence. Because influenced by geographical location this can affect sun exposure to individuals living in the area because the source of vitamin D for humans is exposure to sunlight. For determining differences in serum levels of vitamin D based on residence in the highland and lowland male schizophrenic patient. This study was an analytical study, by RS Jiwa Prof. dr. M. Ildrem Medan, approach to see the comparison 60 samples (30 patients live in the Highland and Lowland). Sample inspection for serum vitamin D using ELFA method. The results showed median levels of vitamin D subjects living in high land Tanah Karo was 22.20ng/mL with minimum-maximum levels of 19.3-34.5ng/mL and in the low land Pemko Medan vitamin D levels higher with median 27.95ng/mL with the minimum-maximum level of vitamin D 20.4-42.6ng/mL. Analysis using the Mann Whitney U test showed significant differences between the levels of vitamin D based on residence with a value of p = 0.001.

  15. A blinded, randomized controlled trial of high-dose vitamin D supplementation to reduce recurrence of bacterial vaginosis. (United States)

    Turner, Abigail Norris; Carr Reese, Patricia; Fields, Karen S; Anderson, Julie; Ervin, Melissa; Davis, John A; Fichorova, Raina N; Roberts, Mysheika Williams; Klebanoff, Mark A; Jackson, Rebecca D


    Low serum vitamin D levels have been associated with increased prevalence of the reproductive tract condition bacterial vaginosis (BV). The objective of this trial was to evaluate the effect of high-dose vitamin D supplementation on BV recurrence. This randomized, placebo-controlled, double-blinded trial enrolled 118 women with symptomatic BV from an urban sexually transmitted disease clinic ( registration NCT01450462). All participants received 500 mg of oral metronidazole twice daily for 7 days. Intervention participants (n = 59) also received 9 doses of 50,000 IU of cholecalciferol (vitamin D3) over 24 weeks; control women (n = 59) received matching placebo. Recurrent BV was assessed via Nugent scoring after 4, 12, and 24 weeks. We assessed the effect of the intervention using an intention-to-treat approach, fitting Cox proportional hazards models to evaluate recurrent BV over the follow-up period. Most participants (74%) were black, with a median age of 26 years. Median presupplementation serum 25-hydroxyvitamin D [25(OH)D] was similar across randomization arms: 16.6 ng/mL in the vitamin D arm and 15.8 ng/mL in the control arm. At trial completion, median 25(OH)D among women receiving vitamin D was 30.5 ng/mL, vs 17.8 ng/mL in control women; 16% of women receiving vitamin D and 57% receiving placebo remained vitamin D deficient (<20 ng/mL). BV prevalence among women randomized to vitamin D was very similar to those randomized to placebo at the 4- and 12-week visits, but by the 24-week visit, BV prevalence was 65% among women in the vitamin D arm and 48% among control women. BV recurrence was not reduced by vitamin D supplementation (intention-to-treat hazard ratio, 1.11; 95% confidence interval, 0.68-1.81). Among women experiencing recurrent BV, median time to recurrence was 13.7 weeks in the vitamin D arm and 14.3 weeks in the control arm. Women receiving vitamin D experienced significant increases in serum 25(OH)D, but this increase was not

  16. Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages. (United States)

    Moganti, Kondaiah; Li, Feng; Schmuttermaier, Christina; Riemann, Sarah; Klüter, Harald; Gratchev, Alexei; Harmsen, Martin C; Kzhyshkowska, Julia


    Hyperglycaemia is a key factor in diabetic pathology. Macrophages are essential regulators of inflammation which can be classified into two major vectors of polarisation: classically activated macrophages (M1) and alternatively activated macrophages (M2). Both types of macrophages play a role in diabetes, where M1 and M2-produced cytokines can have detrimental effects in development of diabetes-associated inflammation and diabetic vascular complications. However, the effect of hyperglycaemia on differentiation and programming of primary human macrophages was not systematically studied. We established a unique model to assess the influence of hyperglycaemia on M1 and M2 differentiation based on primary human monocyte-derived macrophages. The effects of hyperglycaemia on the gene expression and secretion of prototype M1 cytokines TNF-alpha and IL-1beta, and prototype M2 cytokines IL-1Ra and CCL18 were quantified by RT-PCR and ELISA. Hyperglycaemia stimulated production of TNF-alpha, IL-1beta and IL-1Ra during macrophage differentiation. The effect of hyperglycaemia on TNF-alpha was acute, while the stimulating effect on IL-1beta and IL-1Ra was constitutive. Expression of CCL18 was supressed in M2 macrophages by hyperglycaemia. However the secreted levels remained to be biologically significant. Our data indicate that hyperglycaemia itself, without additional metabolic factors induces mixed M1/M2 cytokine profile that can support of diabetes-associated inflammation and development of vascular complications. Copyright © 2016 Elsevier GmbH. All rights reserved.

  17. 2D numerical comparison of trailing edge flaps - UpWind WP1B3

    DEFF Research Database (Denmark)

    Buhl, Thomas; Andersen, Peter Bjørn; Barlas, T.K.

    This report covers the investigations and comparisons of trailing edge flaps carried out by Delft and Risø. The work is a part of the W1B3 work package of the UpWind EU-project. This report covers only 2D test cases with simple control of the trailing edge flap with the objective of keeping CL...... constant. The 5MW UpWind reference turbine is used for the calculations. The section in 75% radius is investigated for three different cases; 1) a wind step from 10m/s to 11m/s, 2) a wind “gust” from 10 m/s to 14m/s in 1 second and followed by 10m/s, 3) finally a turbulent wind series is simulated...

  18. M5-brane as a Nambu-Poisson geometry of a multi-D1-brane theory

    International Nuclear Information System (INIS)

    De Castro, A.; Garcia del Moral, M.P.; Martin, I.; Restuccia, A.


    We introduce a Nambu-Poisson bracket in the geometrical description of the D=11 M5-brane. This procedure allows us, under some assumptions, to eliminate the local degrees of freedom of the antisymmetric field in the M5-brane Hamiltonian and to express it as a D=11 p-brane theory invariant under symplectomorphisms. The explicit expression of the Hamiltonian is obtained. The existence of nontrivial physical configurations annihilating the energy density is shown. Finally, a regularization of the M5-brane in terms of a multi D1-brane theory invariant under the SU(N)xSU(N) group in the limit when N→∞ is constructed

  19. Effects of Vitamin D Supplementation on Serum 25-Hydroxyvitamin D Concentrations in Cirrhotic Patients: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Stefan Pilz


    Full Text Available Background: The liver is crucial for 25-hydroxyvitamin D (25(OHD metabolism, and vitamin D deficiency is highly prevalent in patients with cirrhosis and predicts adverse outcomes. We aimed to evaluate whether vitamin D supplementation in patients with cirrhosis is effective in increasing 25(OHD serum concentrations. Secondary outcome measures included liver function tests (aspartate aminotransferase (AST, alanine aminotransferase (ALT, gamma glutamyltransferase (GGT, and alkaline phosphatase (AP, albumin, International Normalized Ratio (INR, bilirubin, the liver fibrosis marker hyaluronic acid, and parameters of mineral metabolism including parathyroid hormone (PTH. Methods: This is a double-center, double-blind, placebo-controlled study conducted from December 2013 to May 2014 at the Medical University of Graz, and the hospital Hoergas-Enzenbach, Austria. We enrolled 36 consecutive patients with cirrhosis and 25(OHD concentrations below 30 ng/mL. Study participants were randomly allocated to receive either 2800 International Units of vitamin D3 per day as oily drops (n = 18 or placebo (n = 18 for 8 weeks. Results: Thirty-three study participants (mean (SD age: 60 (9 years; 21% females; 25(OHD: 15.6 (7.4 ng/mL completed the trial. The mean treatment effect (95% CI for 25(OHD was 15.2 (8.0 to 22.4 ng/mL (p < 0.001. There was no significant effect on any secondary outcome. Conclusions: In this randomized controlled trial, vitamin D supplementation increases 25(OHD serum concentrations, even in cirrhotic patients.

  20. Lightweight Towed Howitzer Demonstrator. Phase 1 and Partial Phase 2. Volume D1. Part 1. Structural Analysis (Less Cradle and System). (United States)


    X4Cro 7WAW,"G9 N k Y,1i ACCA . 2 JVM ly y,- L OA.0 v roo*Ler t-OAD. FA’ A /"Fi./A/a. (" -A,E’ CNAiv*6:CP A/ ’r/O’,L C4A$4P&4R.* -1MAGC.T?D0 VI.3 Moon...M- S 3D = .. = ==-=== Version 1.1 02/01/85 LTHD muzzle brate thermal load - steel Load Case 1: Loads Node F x FFM - My

  1. On the simultaneous Pell equations x 2 - (4m 2 - 1)y 2 = y 2 - pz 2 ...

    African Journals Online (AJOL)

    Let m be a positive integer, and let p be an odd prime. By using certain properties of Pell and quartic diophantine equations with some elementary number theory methods, we prove that the system of equations x2 - (4m2 - 1)y2 = 1 and y2 - pz2 = 1 has positive integer solutions (x, y, z) if and only if p ≡ 7(mod 8) and m = 1/4 ...

  2. Clinical value of D-Dimer,tumor necrosis factor-a and interleukin-6 levels in type 2 diabetic patients with diabetic retinopathy%2型糖尿病视网膜病变患者血清D-二聚体与肿瘤坏死因子α和白细胞介素6的检测价值

    Institute of Scientific and Technical Information of China (English)



    目的 研究2型糖尿病视网膜病变(DR)患者血清D-二聚体(D-D)、肿瘤坏死因子α(TNF-α和白细胞介素-6(IL-6)水平检测的临床价值.方法 通过眼底血管荧光造影和眼底检查,将80例糖尿病患者分为糖尿病视网膜病变(DR)组(42例)和糖尿病无视网膜病变(NDR)组(38例),另选健康体检者30例作为对照(对照组),对3组D-D、TNF-α和IL-6进行检测.结果 对照组、NDR组及DR组的D-D、TNF-α、IL-6水平分别为(0.34±0.12)mg/L、(4.5±1.7)ng/L、(66.5±19.3)ng/L;(0.59±0.19)mg/L、(15.5±7.9)ng/L、(101.18±30.1)ng/L;(1.08±0.27)ms/L、(42.1±12.6)ng/L、(161.2±48.8)ng/L.糖尿病患者血清D-D、TNF-α和IL-6水平均明显高于对照组(均P<0.05),DR组血清D-D、TNF.仅和IL-6水平均高于NDR组(均P<0.05).结论 DR患者D-D、TNF-α和IL-6水平明显升高,提示此类患者处于高凝状态,且炎症反应可能在糖尿病视网膜DR发展中起重要作用.%Objective To investigate the clinical value of D-dimer (D-D),tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) levels in type 2 diabetic patients with diabetic retinopathy. Methods All the patients had routine FFA and examination of fundus and were divided into two groups based on the results: normal fundus( NDR group n = 38 ) , diabetic retinopathy( DR group n = 42 ). Thirty healthy subjects were used as control group. The serum levels of D-D, IL-6 and TNF-a was detected. Results The serum levels of D-D, IL-6 and TNF-a of type 2 diabetic patients were higher than those of control group statistically (P < 0.05). The serum levels of D-D, IL-6 and TNF-a of DR group were higher than those of NDR group(P <0.05). Conclusions The levels of D-D, IL-6 and TNF-a in type 2 diabetic patients with diabetic retinopathy are higher than those of normal fundus group. The inflammatory reaction may play an important role in the initiation and sustainment of DR.

  3. Pharmacokinetics of 1,25(OH)(2)D(3) and 1alpha(OH)D(3) in normal and uraemic men

    DEFF Research Database (Denmark)

    Brandi, Lisbet; Egfjord, Martin; Olgaard, Klaus


    ,25(OH)(2)D(3) (n=6) protocol. RESULTS: After oral administration of 1,25(OH)(2)D(3) the bioavailability of 1,25(OH)(2)D(3) was 70.6+/-5.8/72.2+/-4.8% in healthy volunteers/uraemic patients (n.s.). After i.v. administration the volume of distribution of 1,25(OH)(2)D(3) was similar, 0.49+/-0.14 vs 0...

  4. Vitamin D and depression in geriatric primary care patients

    Directory of Open Access Journals (Sweden)

    Lapid MI


    Full Text Available Maria I Lapid,1 Stephen S Cha,2 Paul Y Takahashi31Division of Outpatient Consultation, Department of Psychiatry and Psychology, 2Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, 3Division of Primary Care Internal Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USAPurpose: Vitamin D deficiency is common in the elderly. Vitamin D deficiency may affect the mood of people who are deficient. We investigated vitamin D status in older primary care patients and explored associations with depression.Patients and methods: A cross-sectional study was conducted and association analyses were performed. Primary care patients at a single academic medical center who were ≥60 years with serum total 25-hydroxyvitamin D (25[OH]D levels were included in the analysis. The primary outcome was a diagnosis of depression. Frailty scores and medical comorbidity burden scores were collected as predictors.Results: There were 1618 patients with a mean age of 73.8 years (±8.48. The majority (81% had optimal (≥25 ng/mL 25(OHD range, but 17% met mild-moderate (10–24 ng/mL and 3% met severe (<10 ng/mL deficiencies. Those with severe deficiency were older (P < 0.001, more frail (P < 0.001, had higher medical comorbidity burden (P < 0.001, and more frequent depression (P = 0.013. The 694 (43% with depression had a lower 25(OHD than the nondepressed group (32.7 vs 35.0, P = 0.002. 25(OHD was negatively correlated with age (r = −0.070, P = 0.005, frailty (r = −0.113, P < 0.001, and medical comorbidity burden (r = −0.101, P < 0.001. A 25(OHD level was correlated with depression (odds ratio = 0.990 and 95% confidence interval [CI] = 0.983–0.998, P = 0.012. Those with severe vitamin D deficiency were twice as likely to have depression (odds ratio = 2.093 with 95% CI 1.092–4.011, P = 0.026.Conclusion: Vitamin D deficiency was present in a fifth of this older primary care population. Lower vitamin D levels

  5. Nucleic acid sequences encoding D1 and D1/D2 domains of human coxsackievirus and adenovirus receptor (CAR) (United States)

    Freimuth, Paul I.


    The invention provides recombinant human CAR (coxsackievirus and adenovirus receptor) polypeptides which bind adenovirus. Specifically, polypeptides corresponding to adenovirus binding domain D1 and the entire extracellular domain of human CAR protein comprising D1 and D2 are provided. In another aspect, the invention provides nucleic acid sequences encoding these domains and expression vectors for producing the domains and bacterial cells containing such vectors. The invention also includes an isolated fusion protein comprised of the D1 polypeptide fused to a polypeptide which facilitates folding of D1 when expressed in bacteria. The functional D1 domain finds application in a therapeutic method for treating a patient infected with a CAR D1-binding virus, and also in a method for identifying an antiviral compound which interferes with viral attachment. The invention also provides a method for specifically targeting a cell for infection by a virus which binds to D1.

  6. 55-mW, 1.2-V, 12-bit, 100-MSPS Pipeline ADCs for Wireless Receivers (United States)

    Ito, Tomohiko; Kurose, Daisuke; Ueno, Takeshi; Yamaji, Takafumi; Itakura, Tetsuro

    For wireless receivers, low-power 1.2-V 12-bit 100-MSPS pipeline ADCs are fabricated in 90-nm CMOS technology. To achieve low-power dissipation at 1.2V without the degradation of SNR, the configuration of 2.5bit/stage is employed with an I/Q amplifier sharing technique. Furthermore, single-stage pseudo-differential amplifiers are used in a Sample-and-Hold (S/H) circuit and a 1st Multiplying Digital-to-Analog Converter (MDAC). The pseudo-differential amplifier with two-gain-stage transimpedance gain-boosting amplifiers realizes high DC gain of more than 90dB with low power. The measured SNR of the 100-MSPS ADC is 66.7dB at 1.2-V supply. Under that condition, each ADC dissipates only 55mW.

  7. Probing the electronic properties of ternary AnM3n−1B2n (n = 1: A = Ca, Sr; M = Rh, Ir and n = 3: A = Ca, Sr; M = Rh phases: observation of superconductivity

    Directory of Open Access Journals (Sweden)

    Hiroyuki Takeya, Mohammed ElMassalami, Luis A Terrazos, Raul E Rapp, Rodrigo B Capaz, Hiroki Fujii, Yoshihiko Takano, Mathias Doerr and Sergey A Granovsky


    Full Text Available We follow the evolution of the electronic properties of the titled homologous series when n as well as the atomic type of A and M are varied where for n = 1, A = Ca, Sr and M = Rh, Ir while for n = 3, A = Ca, Sr and M = Rh. The crystal structure of n = 1 members is known to be CaRh2B2-type (Fddd, while that of n = 3 is Ca3Rh8B6-type (Fmmm; the latter can be visualized as a stacking of structural fragments from AM3B2 (P6/mmm and AM2B2. The metallic properties of the n = 1 and 3 members are distinctly different: on the one hand, the n = 1 members are characterized by a linear coefficient of the electronic specific heat γ ≈ 3 mJ mol−1 K−2, a Debye temperature θD ≈ 300 K, a normal conductivity down to 2 K and a relatively strong linear magnetoresistivity for fields up to 150 kOe. The n = 3 family, on the other hand, exhibits γ ≈ 18 mJ mol−1 K−2, θD ≈ 330 K, a weak linear magnetoresistivity and an onset of superconductivity (for Ca3Rh8B6, Tc = 4.0 K and Hc2 = 14.5 kOe, while for Sr3Rh8 B6, Tc = 3.4 K and Hc2 ≈ 4.0 kOe. These remarkable differences are consistent with the findings of the electronic band structures and density of state (DOS calculations. In particular, satisfactory agreement between the measured and calculated γ was obtained. Furthermore, the Fermi level, EF, of Ca3Rh8B6 lies at almost the top of a pronounced local DOS peak, while that of CaRh2B2 lies at a local valley: this is the main reason behind the differences between the, e.g., superconducting properties. Finally, although all atoms contribute to the DOS at EF, the contribution of the Rh atoms is the strongest.

  8. Probing the electronic properties of ternary AnM3n−1B2n (n = 1: A = Ca, Sr; M = Rh, Ir and n = 3: A = Ca, Sr; M = Rh) phases: observation of superconductivity (United States)

    Takeya, Hiroyuki; ElMassalami, Mohammed; Terrazos, Luis A; Rapp, Raul E; Capaz, Rodrigo B; Fujii, Hiroki; Takano, Yoshihiko; Doerr, Mathias; Granovsky, Sergey A


    We follow the evolution of the electronic properties of the titled homologous series when n as well as the atomic type of A and M are varied where for n = 1, A = Ca, Sr and M = Rh, Ir while for n = 3, A = Ca, Sr and M = Rh. The crystal structure of n = 1 members is known to be CaRh2B2-type (Fddd), while that of n = 3 is Ca3Rh8B6-type (Fmmm); the latter can be visualized as a stacking of structural fragments from AM3B2 (P6/mmm) and AM2B2. The metallic properties of the n = 1 and 3 members are distinctly different: on the one hand, the n = 1 members are characterized by a linear coefficient of the electronic specific heat γ ≈ 3 mJ mol−1 K−2, a Debye temperature θD ≈ 300 K, a normal conductivity down to 2 K and a relatively strong linear magnetoresistivity for fields up to 150 kOe. The n = 3 family, on the other hand, exhibits γ ≈ 18 mJ mol−1 K−2, θD ≈ 330 K, a weak linear magnetoresistivity and an onset of superconductivity (for Ca3Rh8B6, Tc = 4.0 K and Hc2 = 14.5 kOe, while for Sr3Rh8 B6, Tc = 3.4 K and Hc2 ≈ 4.0 kOe). These remarkable differences are consistent with the findings of the electronic band structures and density of state (DOS) calculations. In particular, satisfactory agreement between the measured and calculated γ was obtained. Furthermore, the Fermi level, EF, of Ca3Rh8B6 lies at almost the top of a pronounced local DOS peak, while that of CaRh2B2 lies at a local valley: this is the main reason behind the differences between the, e.g., superconducting properties. Finally, although all atoms contribute to the DOS at EF, the contribution of the Rh atoms is the strongest. PMID:27877576

  9. Effect of isolated vitamin D supplementation on the rate of falls and postural balance in postmenopausal women fallers: a randomized, double-blind, placebo-controlled trial. (United States)

    Cangussu, Luciana Mendes; Nahas-Neto, Jorge; Orsatti, Claudio Lera; Poloni, Priscila Ferreira; Schmitt, Eneida Boteon; Almeida-Filho, Benedito; Nahas, Eliana Aguiar Petri


    To evaluate the effect of isolated vitamin D supplementation (VITD) on the rate of falls and postural balance in postmenopausal women fallers. In this double-blind, placebo-controlled trial, 160 Brazilian younger postmenopausal women were randomized into two groups: VITD group, vitamin D3 supplementation 1,000 IU/day/orally (n = 80) and placebo group (n = 80). Women with amenorrhea at least 12 months, age 50 to 65 years, and a history of falls (previous 12 months) were included. Those with neurological or musculoskeletal disorders, vestibulopathies, drugs use that could affect balance and osteoporosis were excluded. The intervention time was 9 months. Postural balance was assessed by stabilometry (computerized force platform) and investigation on the occurrence/recurrence of falls was performed by interviews. The plasma concentration of 25-hydroxyvitamin D [25(OH)D] was measured by high-performance liquid chromatography. Statistical analysis was achieved by intention-to-treat, using analysis of variance, Student's t test, Tukey test, chi-square, and logistic regression. After 9 months, mean values of 25(OH)D increased from 15.0 ± 7.5 ng/mL to 27.5 ± 10.4 ng/mL (+45.4%) in the VITD group, and decreased from 16.9 ± 6.7 ng/mL to 13.8 ± 6.0 ng/mL (-18.5%) in the placebo group (P falls was higher in the placebo group (+46.3%) with an adjusted risk of 1.95 (95% confidence interval [CI] 1.23-3.08) times more likely to fall and 2.80 (95% CI 1.43-5.50) times higher for recurrent falls compared to the VITD group (P falls and improvement in postural balance.

  10. 10D massive type IIA supergravities as the uplift of parabolic M2-brane torus bundles

    Energy Technology Data Exchange (ETDEWEB)

    Garcia del Moral, Maria Pilar [Universidad de Antofagasta (Chile). Dept. de Fisica; Restuccia, Alvaro [Universidad de Antofagasta (Chile). Dept. de Fisica; Universidad Simon Bolivar, Caracas (Venezuela, Bolivarian Republic of). Dept. de Fisica


    We remark that the two 10D massive deformations of the N = 2 maximal type IIA supergravity (Romans and HLW supergravity) are associated to the low energy limit of the uplift to 10D of M2-brane torus bundles with parabolic monodromy linearly and non-linearly realized respectively. Romans supergravity corresponds to M2-brane compactified on a twice-punctured torus bundle. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  11. A comparative study of Sus scrofa M. longissimus dorsi with different changes in quality

    Directory of Open Access Journals (Sweden)

    Irina Mikhailovna Chernukha


    Full Text Available The comparative study of Sus scrofa muscle tissue with different defects of quality was carried out. Such analysis methods as determination of water-binding capacity (WBC and pH values, microstructural studies, proteome methods, mass spectrometric methods, high performance liquid chromatography (HPLC and determine the concentration of cathepsin D, calpain 3 and myoglobin were applied in current study. DFD meat was characterized by high pH (6.2 and WBC (93.18%, while PSE - low pH (5.5 and WBC (79.19%. pH and WBC values in NOR pork was medium and averaged 5.9 and 92.05%, respectively. Microstructural studies revealed that fiber in exudative pork was the least and averaged 39.7 µm, normal pork was characterized by diameter of muscle of 45.5 µm, while DFD pork ‑ 48.3 µm. Protein composition of Sus scrofa muscle tissues were also investigated by one-dimensional and two-dimensional electrophoresis. 6 protein fractions were identified by mass spectrometry and confirmed as potential biomarkers of pork quality defects in meat and processes meat product. It also has been shown that PSE pork contains 8 characteristic peptides, NOR - 14, DFD - 18. Cathepsin D, calpain 3 and myoglobin content were measured in pork of different categories. The highest content of cathepsin D, calpain 3 and myoglobin was noticed in PSE pork and averaged 82.16 ±3.30 ng.mL-1; 1.280 ±0.082 ng.mL-1; 3.973 ±0.506 ng.mL-1, respectively. Since the study was carried out on samples of meat 24 hours after slaughter, this work had the prospect to further study of meat with different defects of quality during long-term autolysis.

  12. Children and adolescents with severe mental illness need vitamin D supplementation regardless of disease or treatment. (United States)

    Bonnot, Olivier; Inaoui, Rachida; Raffin-Viard, Marie; Bodeau, Nicolas; Coussieu, Christiane; Cohen, David


    To protect against osteoporosis, keeping the vitamin D blood level (25[OH]D; VDBL) above 30 ng/mL is recommended. It is established that regular intake of vitamin D, calcium intake, and physical exercise contribute to maximizing bone mineral mass during childhood and adolescence. Recent articles suggest that patients with schizophrenia treated with antipsychotics have low VDBL and may have a higher risk of hip fractures in their later years than the general population. To evaluate whether adolescent psychiatric inpatient VDBL is lower than the 30-ng/mL optimal threshold and to document low-VDBL risk factors. We determined the VDBL of all consecutive inpatients from three adolescents units in 2009 (N = 136). Univariate analyses explored the influence on VDBL of (1) well-documented risk factors (e.g., age, gender, ethnic origin, body mass index, or season) and (2) suspected risk factors (e.g., disease type or antipsychotic treatment). All but six patients had a VDBL vitamin D supplementation.

  13. ERK1/2 signaling plays an important role in topoisomerase II poison-induced G2/M checkpoint activation. (United States)

    Kolb, Ryan H; Greer, Patrick M; Cao, Phu T; Cowan, Kenneth H; Yan, Ying


    Topo II poisons, which target topoisomerase II (topo II) to generate enzyme mediated DNA damage, have been commonly used for anti-cancer treatment. While clinical evidence demonstrate a capability of topo II poisons in inducing apoptosis in cancer cells, accumulating evidence also show that topo II poison treatment frequently results in cell cycle arrest in cancer cells, which was associated with subsequent resistance to these treatments. Results in this report indicate that treatment of MCF-7 and T47D breast cancer cells with topo II poisons resulted in an increased phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and an subsequent induction of G2/M cell cycle arrest. Furthermore, inhibition of ERK1/2 activation using specific inhibitors markedly attenuated the topo II poison-induced G2/M arrest and diminished the topo II poison-induced activation of ATR and Chk1 kinases. Moreover, decreased expression of ATR by specific shRNA diminished topo II poison-induced G2/M arrest but had no effect on topo II poison-induced ERK1/2 activation. In contrast, inhibition of ERK1/2 signaling had little, if any, effect on topo II poison-induced ATM activation. In addition, ATM inhibition by either incubation of cells with ATM specific inhibitor or transfection of cells with ATM specific siRNA did not block topo II poison-induced G2/M arrest. Ultimately, inhibition of ERK1/2 signaling greatly enhanced topo II poison-induced apoptosis. These results implicate a critical role for ERK1/2 signaling in the activation of G2/M checkpoint response following topo II poison treatment, which protects cells from topo II poison-induced apoptosis.

  14. Heterogeneity in serum 25-hydroxy-vitamin D response to cholecalciferol in elderly women with secondary hyperparathyroidism and vitamin D deficiency. (United States)

    Giusti, Andrea; Barone, Antonella; Pioli, Giulio; Girasole, Giuseppe; Razzano, Monica; Pizzonia, Monica; Pedrazzoni, Mario; Palummeri, Ernesto; Bianchi, Gerolamo


    To compare the effects on parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25(OH)D) of two dosing regimens of cholecalciferol in women with secondary hyperparathyroidism (sHPTH) and hypovitaminosis D and to investigate variables affecting 25(OH)D response to cholecalciferol. Randomized-controlled trial with 6-month follow-up. Two osteoporosis centers in northern Italy. Sixty community-dwelling women aged 65 and older with sHPTH and hypovitaminosis D, creatinine clearance greater than 65 mL/min and without diseases or drugs known to influence bone and vitamin D metabolism. Cholecalciferol 300,000 IU every 3 months, once at baseline and once at 3 months (intermittent D(3) group) or cholecalciferol 1,000 IU/day (daily D(3) group). Serum PTH, 25(OH)D, calcium, bone-specific alkaline phosphatase, β-C-terminal telopeptide of type I collagen, phosphate, 24-hour urinary calcium excretion. The two groups had similar baseline characteristics. All participants had vitamin D deficiency [25(OH)DD(3) group, n=18; daily D(3) group, n=18). After 3 and 6 months, both groups had a significant increase in 25(OH)D and a reduction in PTH. Mean absolute increase ± standard deviation of 25(OH)D at 6 months was higher in the intermittent D(3) group (22.7±11.8 ng/mL) than in the daily D(3) group (13.7±6.7 ng/mL, PD(3) group reaching desirable serum concentration of 25(OH)D≥30 ng/mL (55% in the intermittent D(3) group vs 20% in the daily D(3) group, PD response to cholecalciferol showed a wide variability. In a logistic regression analysis, body mass index and type of treatment appeared to be significantly associated with normalization of 25(OH)D values. Cholecalciferol 300,000 IU every 3 months was more effective than 1,000 IU daily in correcting vitamin D deficiency, although the two groups achieved similar effects on PTH at 6 months. Only 55% of the higher-dose intermittent group reached desirable concentrations of 25(OH)D, suggesting that yet-higher doses will be required for


    Yasmeh, Joseph; Farpour, Farzin; Rizzo, Vincent; Kheradnam, Sharon; Sachmechi, Issac


    Vitamin D deficiency is associated with several autoimmune diseases. This study assessed whether vitamin D deficiency is associated with Hashimoto thyroiditis (HT). Two groups of patients were selected for which serum 25-hydroxyvitamin D (25(OH)D) levels had been measured: (1) a study group of patients diagnosed with HT as indicated by thyroid antibodies, and (2) a healthy control group. Each group was separated by sex and then controlled for age and body mass index (BMI). Groups' mean 25(OH)D levels were compared by analysis of variance (ANOVA), and percent frequencies of vitamin D sufficiency, insufficiency, and deficiency were compared with a Z-test. The correlations between 25(OH)D levels and thyroid antibodies and thyroid-stimulating hormone (TSH) levels were also tested. The mean 25(OH)D levels for the HT and control groups were significantly different in females (30.75 vs. 27.56 ng/mL, respectively) but not in males (14.24 vs. 13.26 ng/mL). HT females had a higher rate of vitamin D sufficiency (51.7% vs. 31.1%) and a lower rate of insufficiency (48.3% vs. 68.9%) relative to control females. No such differences were found in the male groups. None of the females were vitamin D deficient, but almost all males were. A significant (P = .016) positive correlation (rs = 0.436) between 25(OH)D and TPOAb was observed in males. HT is not associated with higher rates of vitamin D deficiency relative to a control group. BMI = body mass index HT = Hashimoto thyroiditis 25(OH)D = 25-hydroxyvitamin D TgAb = thyroglobulin antibody TSH = thyroid-stimulating hormone TPOAb = thyroid-peroxidase antibody VDR = Vitamin D receptor.

  16. SAXS analysis of a soluble cytosolic NgBR construct including extracellular and transmembrane domains.

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    Joshua Holcomb

    Full Text Available The Nogo-B receptor (NgBR is involved in oncogenic Ras signaling through directly binding to farnesylated Ras. It recruits farnesylated Ras to the non-lipid-raft membrane for interaction with downstream effectors. However, the cytosolic domain of NgBR itself is only partially folded. The lack of several conserved secondary structural elements makes this domain unlikely to form a complete farnesyl binding pocket. We find that inclusion of the extracellular and transmembrane domains that contain additional conserved residues to the cytosolic region results in a well folded protein with a similar size and shape to the E.coli cis-isoprenyl transferase (UPPs. Small Angle X-ray Scattering (SAXS analysis reveals the radius of gyration (Rg of our NgBR construct to be 18.2 Å with a maximum particle dimension (Dmax of 61.0 Å. Ab initio shape modeling returns a globular molecular envelope with an estimated molecular weight of 23.0 kD closely correlated with the calculated molecular weight. Both Kratky plot and pair distribution function of NgBR scattering reveal a bell shaped peak which is characteristic of a single globularly folded protein. In addition, circular dichroism (CD analysis reveals that our construct has the secondary structure contents similar to the UPPs. However, this result does not agree with the currently accepted topological orientation of NgBR which might partition this construct into three separate domains. This discrepancy suggests another possible NgBR topology and lends insight into a potential molecular basis of how NgBR facilitates farnesylated Ras recruitment.

  17. Quercetin inhibits the poly(dA:dT)-induced secretion of IL-18 via down-regulation of the expressions of AIM2 and pro-caspase-1 by inhibiting the JAK2/STAT1 pathway in IFN-γ-primed human keratinocytes. (United States)

    Lee, Kyung-Mi; Kang, Jung Hoon; Yun, Mihee; Lee, Seong-Beom


    Quercetin, a polyphenol, belongs to a class of flavonoids that exerts anti-inflammatory effects. Interleukin (IL)-18 is a member of the IL-1 family cytokine that regulates immune responses and is implicated in various inflammatory skin diseases. Absent in melanoma 2 (AIM2) is a cytosolic double-stranded (ds) DNA sensor that recognizes the dsDNA of a microbial or host origin. Binding of dsDNA to AIM2 simulates caspase-1-dependent inflammasome activity, which leads to the production of IL-1β and IL-18. Increased levels of AIM2 have been observed in patients with inflammatory skin diseases. In the current study, we investigated the issue of whether or how Quercetin attenuates poly (dA:dT), a synthetic analog of microbial dsDNA, -induced IL-18 secretion in IFN-γ-primed human keratinocytes. Treatment with 5 and 10 μM of Quercetin inhibited the poly (dA:dT)-induced secretion of IL-18 after IFN-γ priming and before poly (dA:dT)-induced AIM2 activation. In addition, treatment with Quercetin at 10 μM, significantly inhibited the phosphorylation of JAK2 and STAT1, and the nuclear translocation of phosphorylated STAT1 in poly (dA:dT)-treated and IFN-γ-primed keratinocytes. These results suggest that treatment with Quercetin inhibits the poly (dA:dT)-induced secretion of IL-18 via down-regulation of the expressions of AIM2 and pro-caspase-1 by inhibiting the JAK2/STAT1 pathway in IFN-γ-primed keratinocytes. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. 5-Isopropylidene-1,3-dithiolo[4,5-d][