Gadolinium photoionization process

DOEpatents

Paisner, Jeffrey A.; Comaskey, Brian J.; Haynam, Christopher A.; Eggert, Jon H.

1993-01-01

A method is provided for selective photoionization of the odd-numbered atomic mass gadolinium isotopes 155 and 157. The selective photoionization is accomplished by circular or linear parallel polarized laser beam energy effecting a three-step photoionization pathway.

Gadolinium-hydrogen ion exchange of zirconium phosphate

NASA Technical Reports Server (NTRS)

Liu, D. C.; Power, J. L.

1972-01-01

The Gd(+3)/H(+) ion exchange on a commercial zirconium phosphate ion exchanger was investigated in chloride, sulfate, and phosphate solutions of Gd(+3) at gadolinium concentrations of 0.001 to 1 millimole per cc and in the pH range of 0 to 3.5. Relatively low Gd(+3) capacities, in the range of 0.01 to 0.1 millimole per g of ion exchanger were found at room temperature. A significant difference in Gd(+3) sorption was observed, depending on whether the ion exchanger was converted from initial conditions of greater or lesser Gd(+3) sorption than the specific final conditions. Correlations were found between decrease in Gd(+3) capacity and loss of exchanger phosphate groups due to hydrolysis during washing and between increase in capacity and treatment with H3PO4. Fitting of the experimental data to ideal ion exchange equilibrium expressions indicated that each Gd(+3) ion is sorbed on only one site of the ion exchanger. The selectivity quotient was determined to be 2.5 + or - 0.4 at room temperature on gadolinium desorption in chloride solutions.

Gadolinium-Induced Fibrosis.

PubMed

Todd, Derrick J; Kay, Jonathan

2016-01-01

Gadolinium-based contrast agents (GBCAs), once believed to be safe for patients with renal disease, have been strongly associated with nephrogenic systemic fibrosis (NSF), a severe systemic fibrosing disorder that predominantly afflicts individuals with advanced renal dysfunction. We provide a historical perspective on the appearance and disappearance of NSF, including its initial recognition as a discrete clinical entity, its association with GBCA exposure, and the data supporting a causative relationship between GBCA exposure and NSF. On the basis of this body of evidence, we propose that the name gadolinium-induced fibrosis (GIF) more accurately reflects the totality of knowledge regarding this disease. Use of high-risk GBCAs, such as formulated gadodiamide, should be avoided in patients with renal disease. Restriction of GBCA use in this population has almost completely eradicated new cases of this debilitating condition. Emerging antifibrotic therapies may be useful for patients who suffer from GIF.

Hyperintense Dentate Nuclei on T1-Weighted MRI: Relation to Repeat Gadolinium Administration

PubMed Central

Adin, M.E.; Kleinberg, L.; Vaidya, D.; Zan, E.; Mirbagheri, S.; Yousem, D.M.

2016-01-01

BACKGROUND AND PURPOSE A hyperintense appearance of the dentate nucleus on T1-weighted MR images has been related to various clinical conditions, but the etiology remains indeterminate. We aimed to investigate the possible associations between a hyperintense appearance of the dentate nucleus on T1-weighted MR images in patients exposed to radiation and factors including, but not limited to, the cumulative number of contrast-enhanced MR images, amount of gadolinium administration, dosage of ionizing radiation, and patient demographics. MATERIALS AND METHODS The medical records of 706 consecutive patients who were treated with brain irradiation at The Johns Hopkins Medical Institutions between 1995 and 2010 were blindly reviewed by 2 readers. RESULTS One hundred eighty-four subjects were included for dentate nuclei analysis. Among the 184 subjects who cumulatively underwent 2677 MR imaging studies following intravenous gadolinium administration, 103 patients had hyperintense dentate nuclei on precontrast T1-weighted MR images. The average number of gadolinium-enhanced MR imaging studies performed in the group with normal dentate nuclei was significantly lower than that of the group with hyperintense dentate nuclei. The average follow-up time was 62.5 months. No significant difference was observed between hyperintense and normal dentate nuclei groups in terms of exposed radiation dose, serum creatinine and calcium/phosphate levels, patient demographics, history of chemotherapy, and strength of the scanner. No dentate nuclei abnormalities were found on the corresponding CT scans of patients with hyperintense dentate nuclei (n = 44). No dentate nuclei abnormalities were found in 53 healthy volunteers. CONCLUSIONS Repeat performance of gadolinium-enhanced studies likely contributes to a long-standing hyperintense appearance of dentate nuclei on precontrast T1-weighted-MR images. PMID:26294649

Impact of Impaired Renal Function on Gadolinium Retention After Administration of Gadolinium-Based Contrast Agents in a Mouse Model.

PubMed

Kartamihardja, A Adhipatria P; Nakajima, Takahito; Kameo, Satomi; Koyama, Hiroshi; Tsushima, Yoshito

2016-10-01

The aim of this study was to investigate the impact of impaired renal function on gadolinium (Gd) retention in various organs after Gd-based contrast agent injection. After local animal care and review committee approval, 23 normal mice and 26 with renal failure were divided into 4 treatment groups (Gd-DTPA-BMA, 5 mmol/kg; Gd-DOTA, 5 mmol/kg; GdCl3, 0.02 mmol/kg; and saline, 250 μL). Each agent was intravenously administered on weekdays for 4 weeks. Samples were collected on days 3 (short-term) and 45 (long-term) after the last injection. Gadolinium concentrations were quantified by inductively coupled plasma-mass spectrometry. Three mice with renal failure and 2 normal mice in the GdCl3 group and 1 mouse with renal failure in the Gd-DTPA-BMA group died. In the Gd-DTPA-BMA group, impaired renal function increased short-term Gd retention in the liver, bone, spleen, skin, and kidney (P < 0.01) but did not affect long-term Gd retention. Gd-DTPA-BMA showed higher Gd retention than Gd-DOTA. Although Gd retention in the Gd-DOTA group was generally low, impaired renal function increased only long-term hepatic Gd retention. Hepatic and splenic Gd retentions were significantly higher than other organs' Gd retention in the GdCl3 group (P < 0.01). Renal function did not affect brain Gd retention, regardless of the Gd compound used. The tendency of Gd retention varied according to the agent, regardless of renal function. Although renal impairment increased short-term Gd retention after Gd-DTPA-BMA administration, long-term Gd retention for Gd-based contrast agents was almost unaffected by renal function, suggesting that the chemical structures of retained Gd may not be consistent and some Gd is slowly eliminated after initially being retained.

Gadolinium Chelate Safety in Pregnancy: Barely Detectable Gadolinium Levels in the Juvenile Nonhuman Primate after in Utero Exposure.

PubMed

Prola-Netto, Joao; Woods, Mark; Roberts, Victoria H J; Sullivan, Elinor L; Miller, Christina Ann; Frias, Antonio E; Oh, Karen Y

2018-01-01

Purpose To determine whether gadolinium remains in juvenile nonhuman primate tissue after maternal exposure to intravenous gadoteridol during pregnancy. Materials and Methods Gravid rhesus macaques and their offspring (n = 10) were maintained, as approved by the institutional animal care and utilization committee. They were prospectively studied as part of a pre-existing ongoing research protocol to evaluate the effects of maternal malnutrition on placental and fetal development. On gestational days 85 and 135, they underwent placental magnetic resonance imaging after intravenous gadoteridol administration. Amniocentesis was performed on day 135 prior to administration of the second dose of gadoteridol. After delivery, the offspring were followed for 7 months. Tissue samples from eight different organs and from blood were harvested from each juvenile macaque. Gadolinium levels were measured by using inductively coupled plasma mass spectrometry. Results Gadolinium concentration in the amniotic fluid was 0.028 × 10 -5 %ID/g (percentage injected dose per gram of tissue) 50 days after administration of one gadoteridol dose. Gadolinium was most consistently detected in the femur (mean, 2.5 × 10 -5 %ID/g; range, [0.81-4.1] × 10 -5 %ID/g) and liver (mean, 0.15 × 10 -5 %ID/g; range, [0-0.26] × 10 -5 %ID/g). Levels were undetectable in the remaining sampled tissues, with the exception of one juvenile skin sample (0.07 × 10 -5 %ID/g), one juvenile spleen sample (0.039 × 10 -5 %ID/g), and one juvenile brain (0.095 × 10 -5 %ID/g) and kidney (0.13 × 10 -5 %ID/g) sample. Conclusion The presence of gadoteridol in the amniotic fluid after maternal injection enables confirmation that it crosses the placenta. Extremely low levels of gadolinium are found in juvenile macaque tissues after in utero exposure to two doses of gadoteridol, indicating that a very small amount of gadolinium persists after delivery. © RSNA, 2017.

Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms.

PubMed

Rogosnitzky, Moshe; Branch, Stacy

2016-06-01

Gadolinium chelates are widely used as contrast media for magnetic resonance imaging. The approved gadolinium-based contrast agents (GBCAs) have historically been considered safe and well tolerated when used at recommended dosing levels. However, for nearly a decade, an association between GBCA administration and the development of nephrogenic systemic fibrosis (NSF) has been recognized in patients with severe renal impairment. This has led to modifications in clinical practices aimed at reducing the potential and incidence of NSF development. Newer reports have emerged regarding the accumulation of gadolinium in various tissues of patients who do not have renal impairment, including bone, brain, and kidneys. Despite the observations of gadolinium accumulation in tissues regardless of renal function, very limited clinical data regarding the potential for and mechanisms of toxicity is available. This significant gap in knowledge warrants retrospective cohort study efforts, as well as prospective studies that involve gadolinium ion (Gd(3+)) testing in patients exposed to GBCA. This review examines the potential biochemical and molecular basis of gadolinium toxicity, possible clinical significance of gadolinium tissue retention and accumulation, and methods that can limit gadolinium body burden.

Room temperature ferromagnetic gadolinium silicide nanoparticles

DOEpatents

Hadimani, Magundappa Ravi L.; Gupta, Shalabh; Harstad, Shane; Pecharsky, Vitalij; Jiles, David C.

2018-03-06

A particle usable as T₁ and T₂ contrast agents is provided. The particle is a gadolinium silicide (Gd₅Si₄) particle that is ferromagnetic at temperatures up to 290 K and is less than 2 .mu.m in diameter. An MRI contrast agent that includes a plurality of gadolinium silicide (Gd.sub.5Si.sub.4) particles that are less than 1 .mu.m in diameter is also provided. A method for creating gadolinium silicide (Gd₅Si₄) particles is also provided. The method includes the steps of providing a Gd₅Si₄ bulk alloy; grinding the Gd₅Si₄ bulk alloy into a powder; and milling the Gd₅Si₄ bulk alloy powder for a time of approximately 20 minutes or less.

In vitro comparison of intracranial stent visibility using various concentrations of gadolinium contrast agent under 1.5 T and 3 T MR angiography.

PubMed

Chiang, Chen-Hua; Tseng, Ying-Chi; Chen, Ai-Chi; Huang, Yen-Lin; Chen, David Yen-Ting; Chen, Chi-Jen; Lin, Yen-Kuang; Hsu, Hui-Ling

2017-04-01

MR angiography (MRA) is an increasingly used evaluation method following intracranial stenting. However, the various artifacts created by the stent limit this technique. The purpose of this study was to investigate the effects of various concentrations of gadolinium contrast agent on the visibility and signal characteristics of two stents using the a contrast enhanced MRA technique. Two intracranial stents (Enterprise and Helistent) were placed in polyvinyl chloride tubes as vascular phantoms. They were filled with six different doses of gadolinium contrast agent (1.0, 2.0, 4.0, 6.0, 8.0, and 10.0 mmol/L dimeglumine gadopentetate, respectively) and imaged using 3 T and 1.5 T MR systems. Relative in-stent signal (RIS) was calculated and artificial luminal narrowing (ALN) was obtained using pixel by pixel analysis. The Enterprise stent, performed in both 1.5 T and 3 T MR systems, showed mean RIS values much less than those for the Helistent for all different doses of gadolinium solution. Increased gadolinium concentration resulted in a gradual reduction in RIS values in the Enterprise group. Also, ALN in the Enterprise group showed no or little change with various gadolinium doses. The Enterprise stent demonstrated good luminal visibility regardless of gadolinium concentration. The relative in-stent signals were more predictable in the Enterprise stent with various doses of gadolinium. Therefore, the Enterprise stent has been shown to provide better in-stent visibility compared with the Helistent using various gadolinium doses. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Magnetic resonance characteristics and susceptibility weighted imaging of the brain in gadolinium encephalopathy.

PubMed

Samardzic, Dejan; Thamburaj, Krishnamoorthy

2015-01-01

To report the brain imaging features on magnetic resonance imaging (MRI) in inadvertent intrathecal gadolinium administration. A 67-year-old female with gadolinium encephalopathy from inadvertent high dose intrathecal gadolinium administration during an epidural steroid injection was studied with multisequence 3T MRI. T1-weighted imaging shows pseudo-T2 appearance with diffusion of gadolinium into the brain parenchyma, olivary bodies, and membranous labyrinth. Nulling of cerebrospinal fluid (CSF) signal is absent on fluid attenuation recovery (FLAIR). Susceptibility-weighted imaging (SWI) demonstrates features similar to subarachnoid hemorrhage. CT may demonstrate a pseudo-cerebral edema pattern given the high attenuation characteristics of gadolinium. Intrathecal gadolinium demonstrates characteristic imaging features on MRI of the brain and may mimic subarachnoid hemorrhage on susceptibility-weighted imaging. Identifying high dose gadolinium within the CSF spaces on MRI is essential to avoid diagnostic and therapeutic errors. Copyright © 2013 by the American Society of Neuroimaging.

Density of Gadolinium Nitrate Solutions for the High Flux Isotope Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, Paul Allen; Lee, Denise L

2009-05-01

In late 1992, the High Flux Isotope Reactor (HFIR) was planning to switch the solution contained in the poison injection tank from cadmium nitrate to gadolinium nitrate. The poison injection system is an emergency system used to shut down the reactor by adding a neutron poison to the cooling water. This system must be able to supply a minimum of 69 pounds of gadolinium to the reactor coolant system in order to guarantee that the reactor would become subcritical. A graph of the density of gadolinium nitrate solutions over a concentration range of 5 to 30 wt% and a temperaturemore » range of 15 to 40{sup o}C was prepared. Routine density measurements of the solution in the poison injection tank are made by HFIR personnel, and an adaptation of the original graph is used to determine the gadolinium nitrate concentration. In late 2008, HFIR personnel decided that the heat tracing that was present on the piping for the poison injection system could be removed without any danger of freezing the solution; however, the gadolinium nitrate solution might get as cold as 5{sup o}C. This was outside the range of the current density-concentration correlation, so the range needed to be expanded. This report supplies a new density-concentration correlation that covers the extended temperature range. The correlation is given in new units, which greatly simplifies the calculation that is required to determine the pounds of gadolinium in the tank solution. The procedure for calculating the amount of gadolinium in the HFIR poison injection system is as follows: (1) Calculate the usable volume in the system; (2) Measure the density of the solution; (3) Calculate the gadolinium concentration using the following equation: Gd(lb/ft{sup 3}) = measured density (g/mL) x 34.681 - 34.785; (4) Calculate the amount of gadolinium in the system using the following equation: Amount of Gd(lb) = Gd concentration (lb/ft{sup 3}) x usable volume (ft{sup 3}). The equation in step 3 is exact for a

Structural and magnetic phase transitions in gadolinium under high pressures and low temperatures

DOE PAGES

Samudrala, Gopi K.; Tsoi, Georgiy M.; Weir, Samuel T.; ...

2014-11-07

High pressure structural transition studies have been carried out on rare earth metal gadolinium in a diamond anvil cell at room temperature to 169 GPa. Gadolinium has been compressed to 38% of its initial volume at this pressure. With increasing pressure, a crystal structure sequence of hcp → Smtype→ dhcp → fcc → dfcc → monoclinic has been observed in our studies on gadolinium. The measured equation of state of gadolinium is presented to 169 GPa at ambient temperature. Magnetic ordering temperature of gadolinium has been studied using designer diamond anvils to a pressure of 25 GP and a temperaturemore » of 10 K. The magnetic ordering temperature has been determined from the four-point electrical resistivity measurements carried out on gadolinium. Furthermore, our experiments show that the magnetic transition temperature decreases with increasing pressure to 19 GPa and then increases when gadolinium is subjected to higher pressures.« less

Structural and magnetic phase transitions in gadolinium under high pressures and low temperatures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samudrala, Gopi K.; Tsoi, Georgiy M.; Weir, Samuel T.

High pressure structural transition studies have been carried out on rare earth metal gadolinium in a diamond anvil cell at room temperature to 169 GPa. Gadolinium has been compressed to 38% of its initial volume at this pressure. With increasing pressure, a crystal structure sequence of hcp → Smtype→ dhcp → fcc → dfcc → monoclinic has been observed in our studies on gadolinium. The measured equation of state of gadolinium is presented to 169 GPa at ambient temperature. Magnetic ordering temperature of gadolinium has been studied using designer diamond anvils to a pressure of 25 GP and a temperaturemore » of 10 K. The magnetic ordering temperature has been determined from the four-point electrical resistivity measurements carried out on gadolinium. Furthermore, our experiments show that the magnetic transition temperature decreases with increasing pressure to 19 GPa and then increases when gadolinium is subjected to higher pressures.« less

Structural and magnetic phase transitions in gadolinium under high pressures and low temperatures

NASA Astrophysics Data System (ADS)

Samudrala, Gopi K.; Tsoi, Georgiy M.; Weir, Samuel T.; Vohra, Yogesh K.

2014-10-01

High pressure structural transition studies have been carried out on rare earth metal gadolinium in a diamond anvil cell at room temperature to 169 GPa. Gadolinium has been compressed to 38% of its initial volume at this pressure. With increasing pressure, a crystal structure sequence of hcp → Sm-type → dhcp → fcc → dfcc → monoclinic has been observed in our studies on gadolinium. The measured equation of state of gadolinium is presented to 169 GPa at ambient temperature. Magnetic ordering temperature of gadolinium has been studied using designer diamond anvils to a pressure of 25 GPa and a temperature of 10 K. The magnetic ordering temperature has been determined from the four-point electrical resistivity measurements carried out on gadolinium. Our experiments show that the magnetic transition temperature decreases with increasing pressure to 19 GPa and then increases when gadolinium is subjected to higher pressures.

Gadolinium deposition disease: Initial description of a disease that has been around for a while.

PubMed

Semelka, Richard C; Ramalho, Joana; Vakharia, Ami; AlObaidy, Mamdoh; Burke, Lauren M; Jay, Michael; Ramalho, Miguel

2016-12-01

To describe the clinical manifestations of presumed gadolinium toxicity in patients with normal renal function. Participants were recruited from two online gadolinium toxicity support groups. The survey was anonymous and individuals were instructed to respond to the survey only if they had evidence of normal renal function, evidence of gadolinium in their system beyond 30days of this MRI, and no pre-existent clinical symptoms and/or signs of this type. 42 subjects responded to the survey (age: 28-69, mean 49.1±22.4years). The most common findings were: central pain (n=15), peripheral pain (n=26), headache (n=28), and bone pain (n=26). Only subjects with distal leg and arm distribution described skin thickening (n=22). Clouded mentation and headache were the symptoms described as persistent beyond 3months in 29 subjects. Residual disease was present in all patients. Twenty-eight patients described symptoms following administration of one brand of Gadolinium-Based Contrast Agent (GBCA), 21 after a single GBCA administration and 7 after multiple GBCA administrations, including: gadopentetate dimeglumine, n=9; gadodiamide, n=4; gadoversetamide, n=4; gadobenate dimeglumine, n=4; gadobutrol, n=1; gadoteridol, n=2; and unknown, n=4. Gadolinium toxicity appears to arise following GBCA administration, which appears to contain clinical features seen in Nephrogenic Systemic Fibrosis, but also features not observed in that condition. Copyright © 2016 Elsevier Inc. All rights reserved.

Gadolinium Brain Deposition after Macrocyclic Gadolinium Administration: A Pediatric Case-Control Study.

PubMed

Tibussek, Daniel; Rademacher, Christin; Caspers, Julian; Turowski, Bernd; Schaper, Jörg; Antoch, Gerald; Klee, Dirk

2017-10-01

Purpose To determine whether signal intensity (SI) in T1 sequences as a potential indicator of gadolinium deposition increases after repeated administration of the macrocyclic gadolinium-based contrast agents (GBCAs) gadoteridol and gadoterate meglumine in a pediatric cohort. Materials and Methods This retrospective case-control study of children with brain tumors who underwent nine or more contrast material-enhanced brain magnetic resonance (MR) imaging studies from 2008 to 2015 was approved by the local ethics board. Informed consent was obtained for MR imaging. Twenty-four case patients aged 5-18 years and appropriate control patients with nonpathologic MR neuroimaging findings (and no GBCA administration), matched for age and sex, were inculded. SI was measured on unenhanced T1-weighted MR images for the following five regions of interest (ROIs): the dentate nucleus (DN), pons, substantia nigra (SN), pulvinar thalami, and globus pallidus (GP). Paired t tests were used to compare SI and SI ratios (DN to pons, GP to thalamus) between case patients and control patients. Pearson correlations between relative signal changes and the number of GBCA administrations and total GBCA dose were calculated. Results The mean number of GBCA administrations was 14.2. No significant differences in mean SI for any ROI and no group differences were found when DN-to-pons and GP-to-pulvinar ratios were compared (DN-to-pons ratio in case patients: mean, 1.0083 ± 0.0373 [standard deviation]; DN-to-pons ratio in control patients: mean, 1.0183 ± 0.01917; P = .37; GP-to-pulvinar ratio in case patients: mean, 1.1335 ± 0.04528; and GP-to-pulvinar ratio in control patients: mean, 1.1141 ± 0.07058; P = .29). No correlation was found between the number of GBCA administrations or the total amount of GBCA administered and signal change for any ROI. (Number of GBCA applications: DN: r = -0.254, P = .31; pons: r = -0.097, P = .65; SN: r = -0.194, P = .38; GP: r = -0.175, P = .41; pulvinar: r

Identification and characterization of gadolinium(III) complexes in biological tissue extracts.

PubMed

Kahakachchi, Chethaka L; Moore, Dennis A

2010-07-01

The gadolinium species present in a rat kidney following intravenous administration of a gadolinium-based magnetic resonance contrast agent (Optimark™, Gadoversetamide injection) to a rat was examined in the present study. The major gadolinium species in the supernatant of the rat kidney tissue extracts was determined by reversed-phase liquid chromatography with online inductively coupled plasma optical emission spectrometry (HPLC-ICP-OES). The identity of the compound was established by liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) detection. The principal gadolinium(III) complex in a rat kidney tissue extract was identified as Gd-DTPA-BMEA 24 Hrs and 7 days after a single intravenous injection of Optimark™ (gadoversetamide; Gd-DTPA-BMEA) at a dose of 5 mmol Gd/kg body weight. The study demonstrated for the first time the feasibility of the use of two complementary techniques, HPLC-ICP-OES and HPLC-ESI-MS to study the in vivo behavior of gadolinium-based magnetic resonance contrast media.

Alkali metal and alkali earth metal gadolinium halide scintillators

DOEpatents

Bourret-Courchesne, Edith; Derenzo, Stephen E.; Parms, Shameka; Porter-Chapman, Yetta D.; Wiggins, Latoria K.

2016-08-02

The present invention provides for a composition comprising an inorganic scintillator comprising a gadolinium halide, optionally cerium-doped, having the formula A.sub.nGdX.sub.m:Ce; wherein A is nothing, an alkali metal, such as Li or Na, or an alkali earth metal, such as Ba; X is F, Br, Cl, or I; n is an integer from 1 to 2; m is an integer from 4 to 7; and the molar percent of cerium is 0% to 100%. The gadolinium halides or alkali earth metal gadolinium halides are scintillators and produce a bright luminescence upon irradiation by a suitable radiation.

Gadolinium-enhanced computed tomographic angiography: current status.

PubMed

Rosioreanu, Alex; Alberico, Ronald A; Litwin, Alan; Hon, Man; Grossman, Zachary D; Katz, Douglas S

2005-01-01

This article reviews the research to date, as well as our clinical experience from two institutions, on gadolinium-enhanced computed tomographic angiography (gCTA) for imaging the body. gCTA may be an appropriate examination for the small percentage of patients who would benefit from noninvasive vascular imaging, but who have contraindications to both iodinated contrast and magnetic resonance imaging. gCTA is more expensive than CTA with iodinated contrast, due to the dose of gadolinium administered, and gCTA has limitations compared with CTA with iodinated contrast, in that parenchymal organs are not optimally enhanced at doses of 0.5 mmol/kg or lower. However, in our experience, gCTA has been a very useful problem-solving examination in carefully selected patients. With the advent of 16-64 detector CT, in combination with bolus tracking, we believe that the overall dose of gadolinium needed for diagnostic CTA examinations, while relatively high, can be safely administered.

Gadolinium-based magnetic resonance imaging contrast agents in interventional radiology.

PubMed

Atar, Eli

2004-07-01

Gadolinium-based agents are widely used in magnetic resonance imaging as contrast agents. These agents are radio-opaque enough for diagnostic imaging of the vascular tree by using digitally subtracted images as well as for imaging of the biliary system and the urinary tract. The recommended doses for gadolinium do not impair renal function or cause adverse reactions in patients with iodine sensitivity; thus patients with such conditions can safely undergo diagnostic angiography, either by MRI angiography or by catheterization using gadolinium as contrast agent, for diagnostic and therapeutic purposes.

Solid solutions of gadolinium doped zinc oxide nanorods by combined microwave-ultrasonic irradiation assisted crystallization

NASA Astrophysics Data System (ADS)

Kiani, Armin; Dastafkan, Kamran; Obeydavi, Ali; Rahimi, Mohammad

2017-12-01

Nanocrystalline solid solutions consisting of un-doped and gadolinium doped zinc oxide nanorods were fabricated by a modified sol-gel process utilizing combined ultrasonic-microwave irradiations. Polyvinylpyrrolidone, diethylene glycol, and triethylenetetramine respectively as capping, structure directing, and complexing agents were used under ultrasound dynamic aging and microwave heating to obtain crystalline nanorods. Crystalline phase monitoring, lattice parameters and variation, morphology and shape, elemental analysis, functional groups, reducibility, and the oxidation state of emerged species were examined by PXRD, FESEM, TEM, EDX, FTIR, micro Raman, H2-TPR, and EPR techniques. Results have verified that irradiation mechanism of gelation and crystallization reduces the reaction time, augments the crystal quality, and formation of hexagonal close pack structure of Wurtzite morphology. Besides, dissolution of gadolinium within host lattice involves lattice deformation, unit cell distortion, and angular position variation. Structure related shape and growth along with compositional purity were observed through microscopic and spectroscopic surveys. Furthermore, TPR and EPR studies elucidated more detailed behavior upon exposure to the exerted irradiations and subsequent air-annealing including the formed oxidation states and electron trapping centers, presence of gadolinium, zinc, and oxygen disarrays and defects, as well as alteration in the host unit cell via gadolinium addition.

Thermodynamic properties of gadolinium in Ga-Sn and Ga-Zn eutectic based alloys

NASA Astrophysics Data System (ADS)

Maltsev, Dmitry S.; Volkovich, Vladimir A.; Yamshchikov, Leonid F.; Chukin, Andrey V.

2016-09-01

Thermodynamic properties of gadolinium in Ga-Sn and Ga-Zn eutectic based alloys were studied. Temperature dependences of gadolinium activity in the studied alloys were determined at 573-1073 K employing the EMF method. Solubility of gadolinium in the Ga-Sn and Ga-Zn alloys was measured at 462-1073 K using IMCs sedimentation method. Activity coefficients as well as partial and excess thermodynamic functions of gadolinium in the studied alloys were calculated on the basis of the obtained experimental data.

Effects of gadolinium-based MRI contrast agents on liver tissue.

PubMed

Mercantepe, Tolga; Tümkaya, Levent; Çeliker, Fatma Beyazal; Topal Suzan, Zehra; Çinar, Seda; Akyildiz, Kerimali; Mercantepe, Filiz; Yilmaz, Adnan

2018-04-01

MRI with contrast is often used clinically. However, recent studies have reported a high accumulation of gadolinium-based contrast agents (GBCAs) in kidney, liver, and spleen tissues in several mouse models. To compare the effects on liver tissue of gadolinium-based MRI contrast agents in the light of biochemical and histopathological evaluation. Institutional Review Board (IRB)-approved controlled longitudinal study. In all, 32 male Sprague-Dawley rats were divided into a healthy control group subjected to no procedure (Group 1), a sham group (Group 2), a gadodiamide group (Group 3), and a gadoteric acid group (Group 4). Not applicable. Liver tissues removed at the end of the fifth week and evaluated pathologically (scored Knodell's histological activity index [HAI] method by two histopathologists) immunohistochemical (caspase-3 and biochemical tests (AST, ALT, TAS, TOS, and OSI method by Erel et al) were obtained. Differences between groups were analyzed using the nonparametric Kruskal-Wallis test followed by the Tamhane test, and one-way analysis of variance (ANOVA) followed by Turkey's HSD test. An increase was observed in histological activity scores in sections from rats administered gadodiamide and gadoteric acid, and in caspase-3, AST and ALT values (P < 0.05). In contrast, we determined no change in TOS (P = 0.568 and P = 0.094, respectively), TAS (P = 0.151 and P = 0.055, respectively), or OSI (P = 0.949 and P = 0.494, respectively) values. These data suggest that gadodiamide and gadoteric acid trigger hepatocellular necrosis and apoptosis by causing damage in hepatocytes, although no change occurs in total antioxidant and antioxidant capacity. 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Are gadolinium-based contrast media nephrotoxic? A renal biopsy study.

PubMed

Akgun, Hulya; Gonlusen, Gulfiliz; Cartwright, Joiner; Suki, Wadi N; Truong, Luan D

2006-09-01

Gadolinium-based contrast media were originally introduced as alternatives to iodinated media for magnetic resonance imaging. Although originally thought to be nonnephrotoxic, gadolinium-based contrast media have recently been reported to be associated with acute renal failure; the mechanism and the underlying renal injury are not completely understood. We report what is, to our knowledge, the first renal biopsy in this context. A 56-year-old patient underwent 2 consecutive vascular imaging procedures in conjunction with gadolinium-based contrast medium administration. A few days later, the patient developed acute renal failure. A renal biopsy showed acute tubular cell injury including patchy tubular cell necrosis, tubular cell degeneration, and marked proliferation of tubular cells, together with mild interstitial edema and interstitial inflammation, but without significant glomerular or vascular changes. During supportive therapy, renal function was partially regained. This case emphasizes the potential nephrotoxicity of gadolinium-based contrast media and suggests that the nephrotoxicity is related to potentially reversible acute tubular cell injury.

Technical aspects of MRI signal change quantification after gadolinium-based contrast agents' administration.

PubMed

Ramalho, Joana; Ramalho, Miguel; AlObaidy, Mamdoh; Semelka, Richard C

2016-12-01

Over the last 2years several studies have been published regarding gadolinium deposition in brain structures in patients with normal renal function after repeated administrations of gadolinium-based contrast agents (GBCAs). Most of the publications are magnetic resonance imaging (MRI) based retrospective studies, where gadolinium deposition may be indirectly measured by evaluating changes in T1 signal intensity (SI) in brain tissue, particularly in the dentate nucleus (DN) and/or globus pallidi (GP). The direct correlation between T1 signal changes and gadolinium deposition was validated by human pathology studies. However, the variability of the MR equipment and parameters used across different publications, along with the inherent limitations of MRI to assess gadolinium in human tissues should be acknowledged when interpreting those studies. Nevertheless, MRI studies remain essential regarding gadolinium bio-distribution knowledge. The aim of this paper is to overview current knowledge of technical aspects of T1 signal intensity evaluation by MRI and describe confounding factors, with the intention to achieve higher accuracy and maximize reproducibility. Copyright © 2016 Elsevier Inc. All rights reserved.

Compensated gadolinium-loaded plastic scintillators for thermal neutron detection (and counting)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dumazert, Jonathan; Coulon, Romain; Bertrand, Guillaume H. V.

2015-07-01

Plastic scintillator loading with gadolinium-rich organometallic complexes shows a high potential for the deployment of efficient and cost-effective neutron detectors. Due to the low-energy photon and electron signature of thermal neutron capture by gadolinium-155 and gadolinium-157, alternative treatment to Pulse Shape Discrimination has to be proposed in order to display a trustable count rate. This paper discloses the principle of a compensation method applied to a two-scintillator system: a detection scintillator interacts with photon radiation and is loaded with gadolinium organometallic compound to become a thermal neutron absorber, while a non-gadolinium loaded compensation scintillator solely interacts with the photon partmore » of the incident radiation. Posterior to the nonlinear smoothing of the counting signals, a hypothesis test determines whether the resulting count rate after photon response compensation falls into statistical fluctuations or provides a robust image of a neutron activity. A laboratory prototype is tested under both photon and neutron irradiations, allowing us to investigate the performance of the overall compensation system in terms of neutron detection, especially with regards to a commercial helium-3 counter. The study reveals satisfactory results in terms of sensitivity and orientates future investigation toward promising axes. (authors)« less

Revisiting the Pharmacokinetic Profiles of Gadolinium-Based Contrast Agents: Differences in Long-Term Biodistribution and Excretion.

PubMed

Lancelot, Eric

2016-11-01

Gadolinium-based contrast agents (GBCAs) have been used for years for magnetic resonance imaging examinations. Because of their rapid blood clearance, they were considered as very safe products until some of them were shown to induce nephrogenic systemic fibrosis in patients with renal failure and hypersignals on T1-weighted unenhanced brain scans of patients with normal renal function. To date, these adverse effects have been related almost exclusively to the use of low-stability linear agents, which are more prone to release free gadolinium. The aim of the present meta-analysis was to ascertain the existence of a deep compartment for gadolinium storage in the body and to assess whether all the GBCAs present the same toxicokinetic profile. Applying a systematic literature search methodology, all clinical and preclinical studies reporting time-dependent plasma concentrations and renal excretion data of gadolinium were identified and analyzed. Since the individual data were not available, the analysis focused on the average values per groups of subjects or animals, which had received a given GBCA at a given dose. The rate constants of the distribution phase (α), rapid elimination phase (β), and residual excretion phase (γ) of gadolinium were determined in each group from the plasma concentration (Cp) time curves and the relative urinary excretion rate (rER) time curves, taking the 2-hour time point as a reference. Moreover, as bone may represent a reservoir for long-term gadolinium accumulation and slow release into the blood stream, the time curves of the relative concentration in the bone (rCB) of Gd-labeled GBCAs in mice or rats were analyzed taking day 1 concentrations as a reference. The ratio of gadolinium concentrations in the bone marrow (CBM) as compared with the bone (CB) was also calculated. The relative urinary excretion rate (rER) plots revealed a prolonged residual excretion phase of gadolinium in healthy volunteers, consistent with the existence of

[Rapid imaging in orbito-ocular pathology. Contribution of gadolinium].

PubMed

Pigeau, I; Legeais, J M; D'Hermies, F; Fayet, B; Leport, M; Abenhaim, A; Guinet, C; Levy, C; Renard, G; Vadrot, D

1990-01-01

To evaluate Gradient-Echo Imaging (GEI) in orbito-ocular pathology, 15 volunteers and 34 patients (40 lesions) were examined with GEA T1 and GEA T2 (0.5 T). Results were compared with SE T1 in all cases, with SE T2 in 20 cases and with other imaging modalities (CT). 30 patients were examined before and after injection of gadolinium. Final diagnosis was obtained by surgery or biopsy in 24 cases or by combined results of imaging and clinical findings in 16 cases. Compared with SE, GEA demonstrated a better visualisation of optic nerve, orbital muscles, choroidal-retinal layer, lens capsule and episclera and a better detection of small lesions. It is very helpful for characterisation of lesions containing hemorrhages or paramagnetic components (melanine, gadolinium) or of vascular nature (angioma). Gadolinium was useful for detection of small lesions or characterisation of a few lesions. Thus GEA seems to be an efficient method for the evaluation of orbito-ocular pathology.

Kondo effect and enhanced magnetic properties in gadolinium functionalized carbon nanotube supramolecular complex.

PubMed

Ncube, S; Coleman, C; Strydom, A; Flahaut, E; de Sousa, A; Bhattacharyya, S

2018-05-23

We report on the enhancement of magnetic properties of multiwalled carbon nanotubes (MWNTs) functionalized with a gadolinium based supramolecular complex. By employing a newly developed synthesis technique we find that the functionalization method of the nanocomposite enhances the strength of magnetic interaction leading to a large effective moment of 15.79 µ B and non-superparamagnetic behaviour unlike what has been previously reported. Saturating resistance at low temperatures is fitted with the numerical renormalization group formula verifying the Kondo effect for magnetic impurities on a metallic electron system. Magnetoresistance shows devices fabricated from aligned gadolinium functionalized MWNTs (Gd-Fctn-MWNTs) exhibit spin-valve switching behaviour of up to 8%. This study highlights the possibility of enhancing magnetic interactions in carbon systems through chemical modification, moreover we demonstrate the rich physics that might be useful for developing spin based quantum computing elements based on one-dimensional (1D) channels.

Distribution and chemical forms of gadolinium in the brain: a review.

PubMed

Kanda, Tomonori; Nakai, Yudai; Hagiwara, Akifumi; Oba, Hiroshi; Toyoda, Keiko; Furui, Shigeru

2017-11-01

In the 3 years since residual gadolinium-based contrast agent (GBCA) in the brain was first reported, much has been learned about its accumulation, including the pathway of GBCA entry into the brain, the brain distribution of GBCA and its excretion. Here we review recent progress in understanding the routes of gadolinium deposition in brain structures.

Feasibility and accuracy of dual-layer spectral detector computed tomography for quantification of gadolinium: a phantom study.

PubMed

van Hamersvelt, Robbert W; Willemink, Martin J; de Jong, Pim A; Milles, Julien; Vlassenbroek, Alain; Schilham, Arnold M R; Leiner, Tim

2017-09-01

The aim of this study was to evaluate the feasibility and accuracy of dual-layer spectral detector CT (SDCT) for the quantification of clinically encountered gadolinium concentrations. The cardiac chamber of an anthropomorphic thoracic phantom was equipped with 14 tubular inserts containing different gadolinium concentrations, ranging from 0 to 26.3 mg/mL (0.0, 0.1, 0.2, 0.4, 0.5, 1.0, 2.0, 3.0, 4.0, 5.1, 10.6, 15.7, 20.7 and 26.3 mg/mL). Images were acquired using a novel 64-detector row SDCT system at 120 and 140 kVp. Acquisitions were repeated five times to assess reproducibility. Regions of interest (ROIs) were drawn on three slices per insert. A spectral plot was extracted for every ROI and mean attenuation profiles were fitted to known attenuation profiles of water and pure gadolinium using in-house-developed software to calculate gadolinium concentrations. At both 120 and 140 kVp, excellent correlations between scan repetitions and true and measured gadolinium concentrations were found (R > 0.99, P < 0.001; ICCs > 0.99, CI 0.99-1.00). Relative mean measurement errors stayed below 10% down to 2.0 mg/mL true gadolinium concentration at 120 kVp and below 5% down to 1.0 mg/mL true gadolinium concentration at 140 kVp. SDCT allows for accurate quantification of gadolinium at both 120 and 140 kVp. Lowest measurement errors were found for 140 kVp acquisitions. • Gadolinium quantification may be useful in patients with contraindication to iodine. • Dual-layer spectral detector CT allows for overall accurate quantification of gadolinium. • Interscan variability of gadolinium quantification using SDCT material decomposition is excellent.

Characteristics of Gadolinium Oxide Nanoparticles Using Terahertz Spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Dongkyu; Maeng, Inhee; Son, Joo-Hiuk

2009-04-19

The penetration property of the terahertz electromagnetic (THz) wave is relevant to its use. We used the THz wave spectroscopy system which easily penetrates some materials that do not contain water, e.g., plastic and ceramics. The system has been developed for several purposes, including measuring the properties of semiconductors and bio-materials, and detecting plastic bombs and ceramic knives at airports. It is also used for medical imaging systems, such as magnetic resonance imaging (MRI), at some research institutes. It can show not only the difference in amplitude, but also the difference of the phase of each point of sample. MRImore » technology usually uses contrast agents to enhance the quality of the image. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), made with a heavy metal ion, is commonly used as a clinical MRI contrast agent. Gadolinium oxide (Gd{sub 2}O{sub 3}) nanoparticle is a new contrast agent. It serves to equip the core of each particle with antibodies or ligands. It can freely circulate in blood vessels without amassing in the liver or lungs. This study shows the characteristics of gadolinium oxide nanoparticles to further advance terahertz medical imaging.« less

Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media.

PubMed

Canga, Ana; Kislikova, Maria; Martínez-Gálvez, María; Arias, Mercedes; Fraga-Rivas, Patricia; Poyatos, Cecilio; de Francisco, Angel L M

2014-01-01

Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. Despite being in a group of drugs that were considered safe, report about this potentially serious adverse reaction was a turning point in the administration guidelines of these contrast media. There has been an attempt to establish safety parameters to identify patients with risk factors of renal failure. The close pharmacovigilance and strict observation of current regulations, with special attention being paid to the value of glomerular filtration, have reduced the published cases involving the use of gadolinium-based contrast media. In a meeting between radiologists and nephrologists we reviewed the most relevant aspects currently and recommendations for its prevention.

The dosimetric impact of gadolinium-based contrast media in GBM brain patient plans for a MRI-Linac

NASA Astrophysics Data System (ADS)

Bilal Ahmad, Syed; Paudel, Moti Raj; Sarfehnia, Arman; Kim, Anthony; Pang, Geordi; Ruschin, Mark; Sahgal, Arjun; Keller, Brian M.

2017-08-01

Dosimetric effects of gadolinium based contrast media (Gadovist) were evaluated for the Elekta MRI linear accelerator using the research version of the Monaco treatment planning system (TPS). In order to represent a gadolinium uptake, the contrast was manually assigned to a phantom as well as to the gross tumour volume (GTV) of 6 glioblastoma multiforme (GBM) patients. A preliminary estimate of the dose enhancement, due to gadolinium, was performed using the phantom irradiated with a single beam. A more complicated assessment was performed for the GBM patients using a 7 field IMRT technique. The material table in Monaco was modified in order to identify the presence of a non-biological material. The dose distribution was modelled using GPUMCD (MC algorithm in Monaco) for an unmodified (or default) material table (DMT) as well as for a modified (or custom) material table (CMT) for both the phantom and patients. Various concentrations ranging between 8 and 157 mg ml-1 were used to represent the gadolinium uptake in the patient’s GTV. It was assumed that the gadolinium concentration remained the same for the entire course of radiation treatment. Results showed that at the tissue-Gadovist interface, inside the phantom, dose scored using the DMT was 7% lower compared to that using the CMT for 157 mg ml-1 concentration of gadolinium. Dosimetric differences in the case of the patient study were measured using the DVH parameters. D 50% was higher by 6% when the DMT was used compared to the CMT for dose modelling for a gadolinium concentration of 157 mg ml-1. This difference decreased gradually with decreasing concentration of gadolinium. It was concluded that dosimetric differences can be quantified in Monaco if the tumour-gadolinium concentration is more than 23 mg ml-1. If the gadolinium concentration is lower than 23 mg ml-1, then a correction for the presence of gadolinium may not be necessary in the TPS.

The dosimetric impact of gadolinium-based contrast media in GBM brain patient plans for a MRI-Linac.

PubMed

Ahmad, Syed Bilal; Paudel, Moti Raj; Sarfehnia, Arman; Kim, Anthony; Pang, Geordi; Ruschin, Mark; Sahgal, Arjun; Keller, Brian M

2017-08-01

Dosimetric effects of gadolinium based contrast media (Gadovist) were evaluated for the Elekta MRI linear accelerator using the research version of the Monaco treatment planning system (TPS). In order to represent a gadolinium uptake, the contrast was manually assigned to a phantom as well as to the gross tumour volume (GTV) of 6 glioblastoma multiforme (GBM) patients. A preliminary estimate of the dose enhancement, due to gadolinium, was performed using the phantom irradiated with a single beam. A more complicated assessment was performed for the GBM patients using a 7 field IMRT technique. The material table in Monaco was modified in order to identify the presence of a non-biological material. The dose distribution was modelled using GPUMCD (MC algorithm in Monaco) for an unmodified (or default) material table (DMT) as well as for a modified (or custom) material table (CMT) for both the phantom and patients. Various concentrations ranging between 8 and 157 mg ml -1 were used to represent the gadolinium uptake in the patient's GTV. It was assumed that the gadolinium concentration remained the same for the entire course of radiation treatment. Results showed that at the tissue-Gadovist interface, inside the phantom, dose scored using the DMT was 7% lower compared to that using the CMT for 157 mg ml -1 concentration of gadolinium. Dosimetric differences in the case of the patient study were measured using the DVH parameters. D 50% was higher by 6% when the DMT was used compared to the CMT for dose modelling for a gadolinium concentration of 157 mg ml -1 . This difference decreased gradually with decreasing concentration of gadolinium. It was concluded that dosimetric differences can be quantified in Monaco if the tumour-gadolinium concentration is more than 23 mg ml -1 . If the gadolinium concentration is lower than 23 mg ml -1 , then a correction for the presence of gadolinium may not be necessary in the TPS.

K3 Li3 Gd7 (BO3 )9 : A New Gadolinium-Rich Orthoborate for Cryogenic Magnetic Cooling.

PubMed

Xia, Mingjun; Shen, Shipeng; Lu, Jun; Sun, Young; Li, Rukang

2018-03-02

Magnetic cooling technology based on magnetocaloric effect (MCE) has attracted great interest in obtaining extremely low temperatures, for example, for space exploration. Here, we grew a new gadolinium-rich orthoborate K 3 Li 3 Gd 7 (BO 3 ) 9 (1) as a promising cryogenic magnetic coolant. It exhibits a complicated three dimensional framework constructed from BO 3 groups and gadolinium-oxygen chains. The Gd-O chain consists of two types of clusters of Gd 3 O 20 and Gd 3 O 19 interconnection by Gd(4)O 8 polyhydron. Due to its high gadolinium concentration, a large -ΔS m of 56.6 J kg -1  K -1 for 1 was obtained at 2 K and ΔH=7 T, much larger than that of the commercial benchmark Gd 3 Ga 5 O 12 (GGG) crystal (38.4 J kg -1  K -1 ), suggesting it to be an excellent MCE material. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gadolinium-enhanced cardiovascular magnetic resonance: administered dose in relationship to United States Food and Drug Administration (FDA) guidelines.

PubMed

Nacif, Marcelo S; Arai, Andrew E; Lima, Joao A C; Bluemke, David A

2012-02-29

Myocardial late gadolinium enhancement was originally validated using higher than label-recommended doses of gadolinium chelate. The objective of this study was to evaluate available evidence for various gadolinium dosing regimens used for CMR. The relationship of gadolinium dose warnings (due to nephrogenic systemic fibrosis) announced in 2008 to gadolinium dosing regimens was also examined. We conducted a meta-analysis of peer reviewed publications from January, 2004 to December, 2010. Major subject search headings (MeSh) terms from the National Library of Medicine's PubMed were: contrast media, gadolinium, heart, magnetic resonance imaging; searches were limited to human studies with abstracts published in English. Case reports, review articles, editorials, MRA related papers and all reports that did not indicate gadolinium type or weight-based dose were excluded. For all included references, full text was available to determine the total administered gadolinium dose on a per kg basis. Average and median dose values were weighted by the number of subjects in each study. 399 publications were identified in PubMed; 233 studies matched the inclusion criteria, encompassing 19,934 patients with mean age 54.2 ± 11.4 (range 9.3 to 76 years). 34 trials were related to perfusion testing and 199 to myocardial late gadolinium enhancement. In 2004, the weighted-median and weighted-mean contrast dose were 0.15 and 0.16 ± 0.06 mmol/kg, respectively. Median contrast doses for 2005-2010 were: 0.2 mmol/kg for all years, respectively. Mean contrast doses for the years 2005-2010 were: 0.19 ± 0.03, 0.18 ± 0.04, 0.18 ± 0.10, 0.18 ± 0.03, 0.18 ± 0.04 and 0.18 ± 0.04 mmol/kg, respectively (p for trend, NS). Gadopentetate dimeglumine was the most frequent gadolinium type [114 (48.9%) studies]. No change in mean gadolinium dose was present before, versus after the Food and Drug Administration (FDA) black box warning (p > 0.05). Three multi-center dose ranging trials have been

Gadolinium: Central Metal of the Lanthanoids

ERIC Educational Resources Information Center

Laing, Michael

2009-01-01

The physical and chemical properties of gadolinium are compared with those of the other lanthanoids. Some properties are intermediate between those of lanthanum and lutetium; some between those of barium and hafnium; and others (unexpectedly) between those of ytterbium and lutetium. Both the remarkably high molar heat capacity of the metal and the…

Gadolinium Use in Spine Pain Management Procedures for Patients with Contrast Allergies: Results in 527 Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Safriel, Yair; Ang, Roberto; Ali, Muhammed

2008-03-15

Introduction. To review the safety and efficacy of gadolinium in spine pain management procedures in patients at high risk for a contrast reaction and who are not suitable candidates for the use of standard non-ionic contrast. Methods. We reviewed records over a 61-month period of all image-guided spinal pain management procedures where patients had allergies making them unsuitable candidates for standard non-ionic contrast and where gadolinium was used to confirm needle tip placement prior to injection of medication. Results. Three hundred and four outpatients underwent 527 procedures. A spinal needle was used in all but 41 procedures. Gadolinium was visualizedmore » using portable C-arm fluoroscopy in vivo allowing for confirmation of needle tip location. The gadolinium dose ranged from 0.2 to 10 ml per level. The highest dose received by one patient was 15.83 ml intradiscally during a three-level discogram. Three hundred and one patients were discharged without complication or known delayed complications. One patient had documented intrathecal injection but without sequelae and 2 patients who underwent cervical procedures experienced seizures requiring admission to the intensive care unit. Both the latter patients were discharged without any further complications. Conclusion. Based on our experience we recommend using gadolinium judiciously for needle tip confirmation. We feel more confident using gadolinium in the lumbar spine and in cervical nerve blocks. Gadolinium should probably not be used as an injectate volume expander. The indications for gadolinium use in cervical needle-guided spine procedures are less clear and use of a blunt-tipped needle should be considered.« less

[Gadolinium-based contrast agents for magnetic resonance imaging].

PubMed

Carrasco Muñoz, S; Calles Blanco, C; Marcin, Javier; Fernández Álvarez, C; Lafuente Martínez, J

2014-06-01

Gadolinium-based contrast agents are increasingly being used in magnetic resonance imaging. These agents can improve the contrast in images and provide information about function and metabolism, increasing both sensitivity and specificity. We describe the gadolinium-based contrast agents that have been approved for clinical use, detailing their main characteristics based on their chemical structure, stability, and safety. In general terms, these compounds are safe. Nevertheless, adverse reactions, the possibility of nephrotoxicity from these compounds, and the possibility of developing nephrogenic systemic fibrosis will be covered in this article. Lastly, the article will discuss the current guidelines, recommendations, and contraindications for their clinical use, including the management of pregnant and breast-feeding patients. Copyright © 2014 SERAM. Published by Elsevier Espana. All rights reserved.

Theoretical study of structure and stability of small gadolinium carboxylate complexes in liquid scintillator solvents.

PubMed

Huang, Pin-Wen

2014-09-01

The structural properties of three small gadolinium carboxylate complexes in three liquid scintillator solvents (pseudocumene, linear alkylbenzene, and phenyl xylylethane) were theoretically investigated using density functional theory (B3LYP/LC-RECP) and polarizable continuum model (PCM). The average interaction energy between gadolinium atom and carboxylate ligand (E(int)) and the energy difference of the highest singly occupied molecular orbital and lowest unoccupied molecular orbital (Δ(SL)) were calculated to evaluate and compare the relative stability of these complexes in solvents. The calculation results show that the larger (with a longer alkyl chain) gadolinium carboxylate complex has greater stability than the smaller one, while these gadolinium carboxylates in linear alkylbenzene were found to have greater stability than those in the other two solvents.

Characteristics of Gadolinium Oxide Nanoparticles Using Terahertz Spectroscopy (abstract)

NASA Astrophysics Data System (ADS)

Lee, Dongkyu; Maeng, Inhee; Oh, Seung Jae; Kim, Taekhoon; Cho, Byung Kyu; Lee, Kwangyeol; Son, Joo-Hiuk

2009-04-01

The penetration property of the terahertz electromagnetic (THz) wave is relevant to its use. We used the THz wave spectroscopy system which easily penetrates some materials that do not contain water, e.g., plastic and ceramics. The system has been developed for several purposes, including measuring the properties of semiconductors and bio-materials, and detecting plastic bombs and ceramic knives at airports. It is also used for medical imaging systems, such as magnetic resonance imaging (MRI), at some research institutes. It can show not only the difference in amplitude, but also the difference of the phase of each point of sample. MRI technology usually uses contrast agents to enhance the quality of the image. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), made with a heavy metal ion, is commonly used as a clinical MRI contrast agent. Gadolinium oxide (Gd2O3) nanoparticle is a new contrast agent. It serves to equip the core of each particle with antibodies or ligands. It can freely circulate in blood vessels without amassing in the liver or lungs. This study shows the characteristics of gadolinium oxide nanoparticles to further advance terahertz medical imaging.

Toxicological and pharmacological effects of gadolinium and samarium chlorides

PubMed Central

Haley, T. J.; Raymond, K.; Komesu, N.; Upham, H. C.

1961-01-01

A study has been made of the toxicology and pharmacology of gadolinium and samarium chlorides. The symptoms of acute toxicity following intraperitoneal injection are described. The chronic oral ingestion of both chemicals for 12 weeks produced no effects on growth or the blood picture, and only the male rats receiving gadolinium chloride showed liver damage. The pharmacological responses to both chemicals were mainly depressant on all systems studied, and death was associated with cardiovascular collapse coupled with respiratory paralysis. The greatest damage seen was on abraded skin, where non-healing ulcers were produced by both chemicals, whereas irritation of intact skin and ocular tissues was only transient in nature. PMID:13903826

Porphyrin-containing polyaspartamide gadolinium complexes as potential magnetic resonance imaging contrast agents.

PubMed

Yan, Guo-Ping; Li, Zhen; Xu, Wei; Zhou, Cheng-Kai; Yang, Lian; Zhang, Qiao; Li, Liang; Liu, Fan; Han, Lin; Ge, Yuan-Xing; Guo, Jun-Fang

2011-04-04

Porphyrin-containing polyaspartamide ligands (APTSPP-PHEA-DTPA) were synthesized by the incorporation of diethylenetriaminepentaacetic acid (DTPA) and 5-(4'-aminophenyl)-10,15,20-tris(4'-sulfonatophenyl) porphyrin, trisodium salt (APTSPP) into poly-α,β-[N-(2-hydroxyethyl)-l-aspartamide] (PHEA). These ligands were further reacted with gadolinium chloride to produce macromolecule-gadolinium complexes (APTSPP-PHEA-DTPA-Gd). Experimental data of (1)H NMR, IR, UV and elemental analysis evidenced the formation of the polyaspartamide ligands and gadolinium complexes. In vitro and in vivo property tests indicated that APTSPP-PHEA-DTPA-Gd possessed noticeably higher relaxation effectiveness, less toxicity to HeLa cells, and significantly higher enhanced signal intensities (SI) of the VX2 carcinoma in rabbits with lower injection dose requirement than that of Gd-DTPA. Moreover, APTSPP-PHEA-DTPA-Gd was found to greatly enhance the contrast of MR images of the VX2 carcinoma, providing prolonged intravascular duration, and distinguished the VX2 carcinoma and normal tissues in rabbits according to MR image signal enhancements. These porphyrin-containing polyaspartamide gadolinium complexes can be used as the candidates of contrast agents for targeted MRI to tumors. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Self-assembled gemcitabine-gadolinium nanoparticles for magnetic resonance imaging and cancer therapy.

PubMed

Li, Lele; Tong, Rong; Li, Mengyuan; Kohane, Daniel S

2016-03-01

Nanoparticles with combined diagnostic and therapeutic functions are promising tools for cancer diagnosis and treatment. Here, we demonstrate a theranostic nanoparticle that integrates an active gemcitabine metabolite and a gadolinium-based magnetic resonance imaging agent via a facile supramolecular self-assembly synthesis, where the anti-cancer drug gemcitabine-5'-monophosphate (a phosphorylated active metabolite of the anti-cancer drug gemcitabine) was used to coordinate with Gd(III) to self-assemble into theranostic nanoparticles. The formulation exhibits a strong T1 contrast signal for magnetic resonance imaging of tumors in vivo, with enhanced retention time. Furthermore, the nanoparticles did not require other inert nanocarriers or excipients and thus had an exceptionally high drug loading (55 wt%), resulting in the inhibition of MDA-MB-231 tumor growth in mice. Recent advances in nanoparticle-based drug delivery systems have spurred the development of "theranostic" multifunctional nanoparticles, which combine therapeutic and diagnostic functionalities in a single formulation. Developing simple and efficient synthetic strategies for the construction of nanotheranostics with high drug loading remains a challenge. Here, we demonstrate a theranostic nanoparticle that integrates high loadings of an active gemcitabine metabolite and a gadolinium-based magnetic resonance imaging agent via a facile synthesis. The nanoparticles were better T1 contrast agents than currently used Gd-DTPA and had prolonged retention in tumor. Moreover they exhibited enhanced in vivo antitumor activity compared to free drug in a breast cancer xenograft mouse model. The strategy provides a scalable way to fabricate nanoparticles that enables enhancement of both therapeutic and diagnostic capabilities. Published by Elsevier Ltd.

Proton Relaxivity and Magnetic Hyperthermia Evaluation of Gadolinium Doped Nickel Ferrite Nanoparticles as Potential Theranostic Agents.

PubMed

Yadavalli, Tejabhiram; Raja, Paradeep; Ramaswamy, Shivaraman; Chandrasekharan, Gopalakrishnan; Chennakesavulu, Ramasamy

2017-02-01

This paper outlines the preparation of gadolinium doped nickel ferrite nanoparticles as potential magnetic carriers and longitudinal magnetic resonance imaging contrast agents using hydrothermal method with gadolinium concentration varying from 10% to 40%. A concise effect on the crystal structure was observed at 10% and 20% gadolinium doping, while gadolinium oxide was observed to leach at concentrations exceeding 20%. Further, gadolinium doped nickel ferrites were analyzed for their morphological, magnetic, proton relaxation and magnetic hyperthermia heating properties to understand their potential role as magnetic carrier agents. Low temperature and room temperature magnetic studies conducted on the samples showed comparatively high magnetic saturation with low remanent magnetization. Further, relaxometry studies revealed a high relaxation rate of 6.63 s−1 at a concentration of 0.1 mg/mL. Magnetic hyperthermia studies of the samples at a concentration of 1 mg/mL, assessed that the samples attained a temperature of 68 °C in 240 seconds.

Removal of gadolinium, a neutron poison from the moderator system of nuclear reactors.

PubMed

Rufus, A L; Kumar, Padma S; Jeena, K; Velmurugan, S

2018-01-15

Gadolinium as gadolinium nitrate is used as neutron poison in the moderator system for regulating and controlling the power generation of Pressurized Heavy Water Reactors (PHWR) and proposed to be used in Advanced Heavy Water Reactors (AHWR) owing to its high neutron absorption cross section. Removal of the added gadolinium nitrate (Gd 3+ and NO 3 - ) from the system after its intended use is done using ion exchange resins. In the present investigation, attempts have been made to optimize the ion exchange process for generation of low radioactive waste and maximize utilization of the ion exchange resins by employing different types of resins and different modes of operation. The investigations revealed that use of mixed bed (MB) resin column consisting of Strong Acid Cation (SAC) resin and Strong Base Anion (SBA) resin followed by SAC resin column is efficient in removing the Gd 3+ and NO 3 - from the system besides maintaining the pH of the moderator system in the desirable regime, where gadolinium does not get precipitated as its hydroxide. Copyright © 2017 Elsevier B.V. All rights reserved.

Gadolinium Scandium Gallium Garnet (GSGG) as a Solid-State Laser Host

DTIC Science & Technology

1987-07-01

o*SATI CODSi1.SBEC EM (otne nrvrs fnceayad dniy nb)k ubr ~~~~~~~~ Gadolinium Scandium Gallium Garnet (GSGG)asaSldtteLerHt 17. ABSTRACT 6.SUJCTTEM...certain other garnet materials for replacement. It also addresses the solid-state laser host material Gadolinium Scandium Gal- lium Garnet (GSGG) and its...by neodymium-doped yttrium aluminum garnet (Nd:YAG) or other mate- rials for most applications. In the years after the invention of the ruby laser, in

Gadolinium based contrast agents in current practice: Risks of accumulation and toxicity in patients with normal renal function

PubMed Central

Ranga, Anju; Agarwal, Yatish; Garg, Kanika J

2017-01-01

Despite being decked as the most prized compounds in the nugget box of contrast agents for clinical radiologists, and carrying an indisputable tag of safety of the US Food and Drug Administration for close to three decades, all may not be seemingly well with the family of gadolinium compounds. If the first signs of violations of primum non nocere in relation to gadolinium-based contrast agents (GBCAs) appeared in the millennium year with the first published report of skin fibrosis in patients with compromised renal function, the causal relationship between the development of nephrogenic systemic fibrosis (NSF) and GBCAs, first proposed by two European groups in 2006, further precluded their use in renocompromised patients. The toxicity, pharmacokinetics, and pharmacodynamics of GBCAs, however, has come under hawk-eyed scrutiny with recent reports that gadolinium tends to deposit cumulatively in the brain of patients with normal hepatobiliary function and intact blood–brain barrier. While the jury on the long-term hazard significance of this critical scientific finding is still out, the use of GBCAs must be guided by due clinical diligence, avoidance of repeated doses, and preferring GBCAs with the best safety profiles. PMID:28744073

Gadolinium Endohedral Metallofullerene-Based MRI Contrast Agents

NASA Astrophysics Data System (ADS)

Bolskar, Robert D.

With the ability to encapsulate and carry the highly paramagnetic Gd3+ ion, gadolinium endohedral metallofullerenes or "gadofullerenes" are being explored as alternatives to the chelate complexes that are currently used for contrast-enhanced magnetic resonance imaging (MRI). Reviewed here are the various water-soluble derivatives of the gadofullerenes Gd@C82, Gd@C60, and Gd3N@C80 that have been investigated as MRI contrast agents. The water proton r1 relaxivities of gadofullerenes can be more than an order of magnitude higher than those of clinically used chelate agents. Gadofullerene relaxivity mechanisms have been studied, and multiple factors are found to contribute to their high relaxivities. In vitro and in vivoT1-weighted MRI tests of gadofullerene derivatives have shown their utility as bright image-enhancing agents. The gadofullerene MRI contrast agents are a promising new and unique style of gadolinium carrier for advanced imaging applications, including cellular and molecular imaging.

Clinical application of a gadolinium-based capsule as an MRI contrast agent in slow transit constipation diagnostics.

PubMed

Zhi, M; Zhou, Z; Chen, H; Xiong, F; Huang, J; He, H; Zhang, M; Su, M; Gao, X; Hu, P

2017-06-01

As a traditional method for the assessment of colon dynamics, radio-opaque markers (ROMs) are limited in clinical use because of their ionizing radiation. We compared the accuracy and applicability of gadolinium-based capsules with ROMs in the measurement of colon dynamics in healthy controls and slow transit constipation (STC) patients. Seven patients with STC and nine healthy controls under a normal diet orally consumed ROMs and gadolinium-based capsules simultaneously. All subjects underwent X-ray and magnetic resonance imaging (MRI). Healthy control images were acquired at 12, 24, and 48 h, and STC patient images were acquired at 24, 48, and 72 h. The scores based on the position of the labeling capsules and ROMs in the colon and the colon transit times (CTTs) in the two groups were compared. The CTTs obtained via the ROMs were 34.7±17.4 and 67.3±6.5 h in the healthy controls and STC patients, respectively (P<.05). The CTTs obtained via MRI were 30.9±15.9 and 74.1±7.2 h in the healthy controls and STC patients, respectively (P<.05). The CTTs of the STC patients were significantly longer than the healthy controls. The correlation (r s ) between the scores based on the position of the labeling capsule and ROMs in the healthy group and the STC patients was .880 (P<.05) and .889 (P<.05), respectively. As a MRI contrast label, gadolinium-based capsules exhibit results comparable to ROMs in colon motility measurements. © 2017 John Wiley & Sons Ltd.

A novel cryogenic magnetic refrigerant metal-organic framework based on 1D gadolinium(III) chain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Qun; Li, Peng-Fei; Zou, Zhi-Ming, E-mail: 2014005@glut.edu.cn

2017-02-15

A metal-organic framework (MOF) based on gadolinium ion (Gd{sup 3+}) and tricarboxylate ligand, [Gd(BTPCA)(H{sub 2}O)]·2DMF·3H{sub 2}O (Gd-BTPCA) (H{sub 3}BTPCA =1,1′,1′-(benzene-1,3,5-triyl)tripiperidine-4-carboxylic acid; DMF=dimethylformamide), was synthesized and structurally characterized. The adjacent Gd{sup 3+} ions are intraconnected by the carboxylate groups of the BTPCA{sup 3-} ligands to form a 1D Gd{sup 3+} ion chain. The 1D Gd{sup 3+} ion chains are interconnected by the BTPCA{sup 3-} ligands, giving rise to a 3D framework with 1D open channel. The magnetic studies indicate that Gd-BTPCA exhibits weak ferromagnetic interactions, and acts as a cryogenic magnetic refrigerant having the magnetic entropy change (−ΔS{sub m}) of 20.40more » J kg{sup −1} K{sup −1} for ΔH =7 T at 3 K. - Graphical abstract: A 1D gadolinium(III) chains-based metal-organic framework performed ferromagnetic coupling on the magnetic property. Magnetic investigation reveals that Gd-BTPCA exhibits the entropy change (−ΔS{sub m}) of 20.40 J kg{sup −1} K{sup −1} for ΔH =7 T at 3 K. - Highlights: • The MOF based on gadolinium ion and tricarboxylate ligand was synthesized. • This MOF is connected with 1D Gd{sup 3+} ions chain and the carboxylate groups of BTPCA{sup 3-} ligands. • The magnetic studies indicate that the MOF exhibits the weak ferromagnetic interactions. • Magnetic investigation reveals that the MOF exhibits the high entropy change.« less

Gadolinium-based nanoparticles to improve the hadrontherapy performances.

PubMed

Porcel, Erika; Tillement, Olivier; Lux, François; Mowat, Pierre; Usami, Noriko; Kobayashi, Katsumi; Furusawa, Yoshiya; Le Sech, Claude; Li, Sha; Lacombe, Sandrine

2014-11-01

Nanomedicine is proposed as a novel strategy to improve the performance of radiotherapy. High-Z nanoparticles are known to enhance the effects of ionizing radiation. Recently, multimodal nanoparticles such as gadolinium-based nanoagents were proposed to amplify the effects of x-rays and g-rays and to improve MRI diagnosis. For tumors sited in sensitive tissues, childhood cases and radioresistant cancers, hadrontherapy is considered superior to x-rays and g-rays. Hadrontherapy, based on fast ion radiation, has the advantage of avoiding damage to the tissues behind the tumor; however, the damage caused in front of the tumor is its major limitation. Here, we demonstrate that multimodal gadolinium-based nanoparticles amplify cell death with fast ions used as radiation. Molecular scale experiments give insights into the mechanisms underlying the amplification of radiation effects. This proof-of-concept opens up novel perspectives for multimodal nanomedicine in hadrontherapy, ultimately reducing negative radiation effects in healthy tissues in front of the tumor. Gadolinium-chelating polysiloxane nanoparticles were previously reported to amplify the anti-tumor effects of x-rays and g-rays and to serve as MRI contrast agents. Fast ion radiation-based hadrontherapy avoids damage to the tissues behind the tumor, with a major limitation of tissue damage in front of the tumor. This study demonstrates a potential role for the above nanoagents in optimizing hadrontherapy with preventive effects in healthy tissue and amplified cell death in the tumor. Copyright © 2014 Elsevier Inc. All rights reserved.

Retention of Gadolinium-Based Contrast Agents in Multiple Sclerosis: Retrospective Analysis of an 18-Year Longitudinal Study.

PubMed

Forslin, Y; Shams, S; Hashim, F; Aspelin, P; Bergendal, G; Martola, J; Fredrikson, S; Kristoffersen-Wiberg, M; Granberg, T

2017-07-01

Gadolinium-based contrast agents have been associated with lasting high T1-weighted signal intensity in the dentate nucleus and globus pallidus, with histopathologically confirmed gadolinium retention. We aimed to longitudinally investigate the relationship of multiple gadolinium-based contrast agent administrations to the Signal Intensity Index in the dentate nucleus and globus pallidus and any associations with cognitive function in multiple sclerosis. The Signal Intensity Index in the dentate nucleus and globus pallidus was retrospectively evaluated on T1-weighted MR imaging in an 18-year longitudinal cohort study of 23 patients with MS receiving multiple gadolinium-based contrast agent administrations and 23 healthy age- and sex-matched controls. Participants also underwent comprehensive neuropsychological testing. Patients with MS had a higher Signal Intensity Index in the dentate nucleus ( P < .001), but not in the globus pallidus ( P = .19), compared with non-gadolinium-based contrast agent-exposed healthy controls by an unpaired t test. Increasing numbers of gadolinium-based contrast agent administrations were associated with an increased Signal Intensity Index in the dentate nucleus (β = 0.45, P < .001) and globus pallidus (β = 0.60, P < .001). This association remained stable with corrections for the age, disease duration, and physical disability for both the dentate nucleus (β = 0.43, P = .001) and globus pallidus (β = 0.58, P < .001). An increased Signal Intensity Index in the dentate nucleus among patients with MS was associated with lower verbal fluency scores, which remained significant after correction for several aspects of disease severity (β = -0.40 P = .013). Our data corroborate previous reports of lasting gadolinium retention in brain tissues. An increased Signal Intensity Index in the dentate nucleus and globus pallidus was associated with lower verbal fluency, which does not prove causality but encourages further studies on cognition

Myocardial late gadolinium enhancement in specific cardiomyopathies by cardiovascular magnetic resonance: a preliminary experience.

PubMed

Silva, Caterina; Moon, James C; Elkington, Andrew G; John, Anna S; Mohiaddin, Raad H; Pennell, Dudley J

2007-12-01

Late gadolinium enhancement cardiovascular magnetic resonance (CMR) can visualize myocardial interstitial abnormalities. The aim of this study was to assess whether regions of abnormal myocardium can also be visualized by late enhancement gadolinium CMR in the specific cardiomyopathies. A retrospective review of all referrals for gadolinium CMR with specific cardiomyopathy over 20 months. Nine patients with different specific cardiomyopathies were identified. Late enhancement was demonstrated in all patients, with a mean signal intensity of 390 +/- 220% compared with normal regions. The distribution pattern of late enhancement was unlike the subendocardial late enhancement related to coronary territories found in myocardial infarction. The affected areas included papillary muscles (sarcoid), the mid-myocardium (Anderson-Fabry disease, glycogen storage disease, myocarditis, Becker muscular dystrophy) and the global sub-endocardium (systemic sclerosis, Loeffler's endocarditis, amyloid, Churg-Strauss). Focal myocardial late gadolinium enhancement is found in the specific cardiomyopathies, and the pattern is distinct from that seen in infarction. Further systematic studies are warranted to assess whether the pattern and extent of late enhancement may aid diagnosis and prognostic assessment.

Pediatric Patients Demonstrate Progressive T1-Weighted Hyperintensity in the Dentate Nucleus following Multiple Doses of Gadolinium-Based Contrast Agent.

PubMed

Roberts, D R; Chatterjee, A R; Yazdani, M; Marebwa, B; Brown, T; Collins, H; Bolles, G; Jenrette, J M; Nietert, P J; Zhu, X

2016-12-01

While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent administration in adults, a retrospective series of pediatric patients has not previously been reported, to our knowledge. We investigated the relationship between the number of prior gadolinium-based contrast agent doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that despite differences in pediatric physiology and the smaller gadolinium-based contrast agent doses that pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose-dependent increasing T1 signal in the dentate nucleus. We included children with multiple gadolinium-based contrast agent administrations at our institution. A blinded reader placed ROIs within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, we also performed automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons. Dentate-to-cerebellar white matter and dentate-to pons ratios were compared with the number of gadolinium-based contrast agent administrations. During 20 years at our institution, 280 patients received at least 5 gadolinium-based contrast agent doses, with 1 patient receiving 38 doses. Sixteen patients met the inclusion/exclusion criteria for ROI analysis. Blinded reader dentate-to-cerebellar white matter ratios were significantly associated with gadolinium-based contrast agent doses (r s = 0.77, P = .001). The dentate-to-pons ratio and dentate-to-cerebellar white matter ratios based on automated ROI placement were also significantly correlated with gadolinium-based contrast agent doses (t = 4.98, P < .0001 and t = 2.73, P < .02, respectively). In pediatric patients, the number of prior gadolinium-based contrast agent doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of

The High Radiosensitizing Efficiency of a Trace of Gadolinium-Based Nanoparticles in Tumors

NASA Astrophysics Data System (ADS)

Dufort, Sandrine; Le Duc, Géraldine; Salomé, Murielle; Bentivegna, Valerie; Sancey, Lucie; Bräuer-Krisch, Elke; Requardt, Herwig; Lux, François; Coll, Jean-Luc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier

2016-07-01

We recently developed the synthesis of ultrasmall gadolinium-based nanoparticles (GBN), (hydrodynamic diameter <5 nm) characterized by a safe behavior after intravenous injection (renal clearance, preferential accumulation in tumors). Owing to the presence of gadolinium ions, GBN can be used as contrast agents for magnetic resonance imaging (MRI) and as radiosensitizers. The attempt to determine the most opportune delay between the intravenous injection of GBN and the irradiation showed that a very low content of radiosensitizing nanoparticles in the tumor area is sufficient (0.1 μg/g of particles, i.e. 15 ppb of gadolinium) for an important increase of the therapeutic effect of irradiation. Such a promising and unexpected result is assigned to a suited distribution of GBN within the tumor, as revealed by the X-ray fluorescence (XRF) maps.

In vitro radiosensitizing effects of ultrasmall gadolinium based particles on tumour cells.

PubMed

Mowat, P; Mignot, A; Rima, W; Lux, F; Tillement, O; Roulin, C; Dutreix, M; Bechet, D; Huger, S; Humbert, L; Barberi-Heyob, M; Aloy, M T; Armandy, E; Rodriguez-Lafrasse, C; Le Duc, G; Roux, S; Perriat, P

2011-09-01

Since radiotherapy is widely used in cancer treatment, it is essential to develop strategies which lower the irradiation burden while increasing efficacy and become efficient even in radio resistant tumors. Our new strategy is relying on the development of solid hybrid nanoparticles based on rare-earth such as gadolinium. In this paper, we then evidenced that gadolinium-based particles can be designed to enter efficiently into the human glioblastoma cell line U87 in quantities that can be tuned by modifying the incubation conditions. These sub-5 nm particles consist in a core of gadolinium oxide, a shell of polysiloxane and are functionalized by diethylenetriaminepentaacetic acid (DTPA). Although photoelectric effect is maximal in the [10-100 keV] range, such particles were found to possess efficient in-vitro radiosensitizing properties at an energy of 660 keV by using the "single-cell gel electrophoresis comet assay," an assay that measures the number of DNA damage that occurs during irradiation. Even more interesting, the particles have been evidenced by MTT assays to be also efficient radiosensitizers at an energy of 6 MeV for doses comprised between 2 and 8 Gy. The properties of the gadolinium-based particles give promising opening to a particle-assisted radio-therapy by using irradiation systems already installed in the majority of hospitals.

Addition of lysophospholipids with large head groups to cells inhibits Shiga toxin binding.

PubMed

Ailte, Ieva; Lingelem, Anne Berit Dyve; Kavaliauskiene, Simona; Bergan, Jonas; Kvalvaag, Audun Sverre; Myrann, Anne-Grethe; Skotland, Tore; Sandvig, Kirsten

2016-07-26

Shiga toxin (Stx), an AB5 toxin, binds specifically to the neutral glycosphingolipid Gb3 at the cell surface before being transported into cells. We here demonstrate that addition of conical lysophospholipids (LPLs) with large head groups inhibit Stx binding to cells whereas LPLs with small head groups do not. Lysophosphatidylinositol (LPI 18:0), the most efficient LPL with the largest head group, was selected for in-depth investigations to study how the binding of Stx is regulated. We show that the inhibition of Stx binding by LPI is reversible and possibly regulated by cholesterol since addition of methyl-β-cyclodextrin (mβCD) reversed the ability of LPI to inhibit binding. LPI-induced inhibition of Stx binding is independent of signalling and membrane turnover as it occurs in fixed cells as well as after depletion of cellular ATP. Furthermore, data obtained with fluorescent membrane dyes suggest that LPI treatment has a direct effect on plasma membrane lipid packing with shift towards a liquid disordered phase in the outer leaflet, while lysophosphoethanolamine (LPE), which has a small head group, does not. In conclusion, our data show that cellular treatment with conical LPLs with large head groups changes intrinsic properties of the plasma membrane and modulates Stx binding to Gb3.

Gadolinium-Conjugated Gold Nanoshells for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy

PubMed Central

Coughlin, Andrew J.; Ananta, Jeyarama S.; Deng, Nanfu; Larina, Irina V.; Decuzzi, Paolo

2014-01-01

Multimodal imaging offers the potential to improve diagnosis and enhance the specificity of photothermal cancer therapy. Toward this goal, we have engineered gadolinium-conjugated gold nanoshells and demonstrated that they enhance contrast for magnetic resonance imaging, X-Ray, optical coherence tomography, reflectance confocal microscopy, and two-photon luminescence. Additionally, these particles effectively convert near-infrared light to heat, which can be used to ablate cancer cells. Ultimately, these studies demonstrate the potential of gadolinium-nanoshells for image-guided photothermal ablation. PMID:24115690

The Effect of gadolinium on the ESR response of alanine and ammonium tartrate exposed to thermal neutrons.

PubMed

Marrale, Maurizio; Brai, Maria; Gennaro, Gaetano; Bartolotta, Antonio; D'Oca, Maria Cristina

2008-02-01

Many efforts have been made to develop neutron capture therapy (NCT) for cancer treatment. Among the challenges in using NCT is the characterization of the features of the mixed radiation field and of its components. In this study, we examined the enhancement of the ESR response of pellets of alanine and ammonium tartrate with gadolinium oxide exposed to a thermal neutron beam. In particular, the ESR response of these dosimeters as a function of the gadolinium content inside the dosimeter was analyzed. We found that the addition of gadolinium improves the sensitivity of both alanine and ammonium tartrate. However, the use of gadolinium reduces or abolishes tissue equivalence because of its high atomic number (Z(Gd) = 64). Therefore, it is necessary to find the optimum compromise between the sensitivity to thermal neutrons and the reduction of tissue equivalence. Our analysis showed that a low concentration of gadolinium oxide (of the order of 5% of the total mass of the dosimeter) can enhance the thermal neutron sensitivity more than 13 times with an insignificant reduction of tissue equivalence.

Gadolinium-loaded Plastic Scintillators for Thermal Neutron Detection using Compensation

NASA Astrophysics Data System (ADS)

Dumazert, Jonathan; Coulon, Romain; Hamel, Matthieu; Carrel, Frédérick; Sguerra, Fabien; Normand, Stéphane; Méchin, Laurence; Bertrand, Guillaume H. V.

2016-06-01

Plastic scintillator loading with gadolinium-rich organometallic complexes shows a high potential for the deployment of efficient and cost-effective neutron detectors. Due to the low-energy photon and electron signature of thermal neutron capture by Gd-155 and Gd-157, alternative treatment to pulse-shape discrimination has to be proposed in order to display a count rate. This paper discloses the principle of a compensation method applied to a two-scintillator system: a detection scintillator interacts with photon and fast neutron radiation and is loaded with gadolinium organometallic compound to become a thermal neutron absorber, while a not-gadolinium loaded compensation scintillator solely interacts with the fast neutron and photon part of incident radiation. After the nonlinear smoothing of the counting signals, a hypothesis test determines whether the resulting count rate post-background response compensation falls into statistical fluctuations or provides a robust indication of neutron activity. Laboratory samples are tested under both photon and neutron irradiations, allowing the authors to investigate the performance of the overall detection system in terms of sensitivity and detection limits, especially with regards to a similar-active volume He-3 based commercial counter. The study reveals satisfactory figures of merit in terms of sensitivity and directs future investigation toward promising paths.

Tracing gadolinium-based contrast agents from surface water to drinking water by means of speciation analysis.

PubMed

Birka, Marvin; Wehe, Christoph A; Hachmöller, Oliver; Sperling, Michael; Karst, Uwe

2016-04-01

In recent decades, a significant amount of anthropogenic gadolinium has been released into the environment as a result of the broad application of contrast agents for magnetic resonance imaging (MRI). Since this anthropogenic gadolinium anomaly has also been detected in drinking water, it has become necessary to investigate the possible effect of drinking water purification on these highly polar microcontaminats. Therefore, a novel highly sensitive method for speciation analysis of gadolinium is presented. For that purpose, the hyphenation of hydrophilic interaction liquid chromatography (HILIC) and inductively coupled plasma-mass spectrometry (ICP-MS) was employed. In order to enhance the detection power, sample introduction was carried out by ultrasonic nebulization. In combination with a novel HILIC method using a diol-based stationary phase, it was possible to achieve superior limits of detection for frequently applied gadolinium-based contrast agents below 20pmol/L. With this method, the contrast agents Gd-DTPA, Gd-DOTA and Gd-BT-DO3A were determined in concentrations up to 159pmol/L in samples from several waterworks in a densely populated region of Germany alongside the river Ruhr as well as from a waterworks near a catchment lake. Thereby, the direct impact of anthropogenic gadolinium species being present in the surface water on the amount of anthropogenic gadolinium in drinking water was shown. There was no evidence for the degradation of contrast agents, the release of Gd(3+) or the presence of further Gd species. Copyright © 2016 Elsevier B.V. All rights reserved.

A polymeric fastener can easily functionalize liposome surfaces with gadolinium for enhanced magnetic resonance imaging.

PubMed

Smith, Cartney E; Shkumatov, Artem; Withers, Sarah G; Yang, Binxia; Glockner, James F; Misra, Sanjay; Roy, Edward J; Wong, Chun-Ho; Zimmerman, Steven C; Kong, Hyunjoon

2013-11-26

Common methods of loading magnetic resonance imaging (MRI) contrast agents into nanoparticles often suffer from challenges related to particle formation, complex chemical modification/purification steps, and reduced contrast efficiency. This study presents a simple, yet advanced process to address these issues by loading gadolinium, an MRI contrast agent, exclusively on a liposome surface using a polymeric fastener. The fastener, so named for its ability to physically link the two functional components together, consisted of chitosan substituted with diethylenetriaminepentaacetic acid (DTPA) to chelate gadolinium, as well as octadecyl chains to stabilize the modified chitosan on the liposome surface. The assembly strategy, mimicking the mechanisms by which viruses and proteins naturally anchor to a cell, provided greater T1 relaxivity than liposomes loaded with gadolinium in both the interior and outer leaflet. Gadolinium-coated liposomes were ultimately evaluated in vivo using murine ischemia models to highlight the diagnostic capability of the system. Taken together, this process decouples particle assembly and functionalization and, therefore, has considerable potential to enhance imaging quality while alleviating many of the difficulties associated with multifunctional particle fabrication.

A Polymeric Fastener can Easily Functionalize Liposome Surfaces with Gadolinium for Enhanced Magnetic Resonance Imaging

PubMed Central

Smith, Cartney E.; Shkumatov, Artem; Withers, Sarah G.; Glockner, James F.; Misra, Sanjay; Roy, Edward J.; Wong, Chun-Ho; Zimmerman, Steven C.; Kong, Hyunjoon

2013-01-01

Common methods of loading magnetic resonance imaging (MRI) contrast agents into nanoparticles often suffer from challenges related to particle formation, complex chemical modification/purification steps, and reduced contrast efficiency. This study presents a simple, yet advanced process to address these issues by loading gadolinium, an MRI contrast agent, exclusively on a liposome surface using a polymeric fastener. The fastener, so named for its ability to physically link the two functional components together, consisted of chitosan substituted with diethylenetriaminepentaacetic acid (DTPA) to chelate gadolinium, as well as octadecyl chains to stabilize the modified chitosan on the liposome surface. The assembly strategy, mimicking the mechanisms by which viruses and proteins naturally anchor to a cell, provided greater T1 relaxivity than liposomes loaded with gadolinium in both the interior and outer leaflet. Gadolinium-coated liposomes were ultimately evaluated in vivo using murine ischemia models to highlight the diagnostic capability of the system. Taken together, this process decouples particle assembly and functionalization, and therefore has considerable potential to enhance imaging quality while alleviating many of the difficulties associated with multifunctional particle fabrication. PMID:24083377

Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain.

PubMed

Taoka, Toshiaki; Naganawa, Shinji

2018-04-10

After Kanda's first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the 'glymphatic system', which is a coined word that combines 'gl' for glia cell and 'lymphatic' system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue.

Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain

PubMed Central

Taoka, Toshiaki; Naganawa, Shinji

2018-01-01

After Kanda’s first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the ‘glymphatic system’, which is a coined word that combines ‘gl’ for glia cell and ‘lymphatic’ system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue. PMID:29367513

High longitudinal relaxivity of ultra-small gadolinium oxide prepared by microsecond laser ablation in diethylene glycol

NASA Astrophysics Data System (ADS)

Luo, Ningqi; Tian, Xiumei; Xiao, Jun; Hu, Wenyong; Yang, Chuan; Li, Li; Chen, Dihu

2013-04-01

Ultra-small gadolinium oxide (Gd2O3) can be used as T1-weighted Magnetic Resonance Imaging (MRI) contrast agent own to its high longitudinal relaxivity (r1) and has attracted intensive attention in these years. In this paper, ultra-small Gd2O3 nanoparticles of 3.8 nm in diameter have been successfully synthesized by a microsecond laser ablating a gadolinium (Gd) target in diethylene glycol (DEG). The growth inhibition effect induced by the large viscosity of DEG makes it possible to synthesize ultra-small Gd2O3 by laser ablation in DEG. The r1 value and T1-weighted MR images are measured by a 3.0 T MRI spectroscope. The results show these nanoparticles with a high r1 value of 9.76 s-1 mM-1 to be good MRI contrast agents. We propose an explanation for the high r1 value of ultra-small Gd2O3 by considering the decreasing factor (surface to volume ratio of the nanoparticles, S/V) and the increasing factor (water hydration number of the Gd3+ on Gd2O3 surface, q), which offer a new look into the relaxivity studies of MRI contrast agents. Our research provides a new approach to preparing ultra-small Gd2O3 of high r1 value by laser ablation in DEG and develops the understanding of high relaxivity of ultra-small Gd2O3 MRI contrast agents.

Do we need gadolinium-based contrast medium for brain magnetic resonance imaging in children?

PubMed

Dünger, Dennis; Krause, Matthias; Gräfe, Daniel; Merkenschlager, Andreas; Roth, Christian; Sorge, Ina

2018-06-01

Brain imaging is the most common examination in pediatric magnetic resonance imaging (MRI), often combined with the use of a gadolinium-based contrast medium. The application of gadolinium-based contrast medium poses some risk. There is limited evidence of the benefits of contrast medium in pediatric brain imaging. To assess the diagnostic gain of contrast-enhanced sequences in brain MRI when the unenhanced sequences are normal. We retrospectively assessed 6,683 brain MR examinations using contrast medium in children younger than 16 years in the pediatric radiology department of the University Hospital Leipzig to determine whether contrast-enhanced sequences delivered additional, clinically relevant information to pre-contrast sequences. All examinations were executed using a 1.5-T or a 3-T system. In 8 of 3,003 (95% confidence interval 0.12-0.52%) unenhanced normal brain examinations, a relevant additional finding was detected when contrast medium was administered. Contrast enhancement led to a change in diagnosis in only one of these cases. Children with a normal pre-contrast brain MRI rarely benefit from contrast medium application. Comparing these results to the risks and disadvantages of a routine gadolinium application, there is substantiated numerical evidence for avoiding routine administration of gadolinium in a pre-contrast normal MRI examination.

Accumulation of MRI contrast agents in malignant fibrous histiocytoma for gadolinium neutron capture therapy.

PubMed

Fujimoto, T; Ichikawa, H; Akisue, T; Fujita, I; Kishimoto, K; Hara, H; Imabori, M; Kawamitsu, H; Sharma, P; Brown, S C; Moudgil, B M; Fujii, M; Yamamoto, T; Kurosaka, M; Fukumori, Y

2009-07-01

Neutron-capture therapy with gadolinium (Gd-NCT) has therapeutic potential, especially that gadolinium is generally used as a contrast medium in magnetic resonance imaging (MRI). The accumulation of gadolinium in a human sarcoma cell line, malignant fibrosis histiocytoma (MFH) Nara-H, was visualized by the MRI system. The commercially available MRI contrast medium Gd-DTPA (Magnevist, dimeglumine gadopentetate aqueous solution) and the biodegradable and highly gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles (Gd-nanoCPs) were prepared as MRI contrast agents. The MFH cells were cultured and collected into three falcon tubes that were set into the 3-tesra MRI system to acquire signal intensities from each pellet by the spin echo method, and the longitudinal relaxation time (T1) was calculated. The amount of Gd in the sample was measured by inductively coupled plasma atomic emission spectrography (ICP-AES). The accumulation of gadolinium in cells treated with Gd-nanoCPs was larger than that in cells treated with Gd-DTPA. In contrast, and compared with the control, Gd-DTPA was more effective than Gd-nanoCPs in reducing T1, suggesting that the larger accumulation exerted the adverse effect of lowering the enhancement of MRI. Further studies are warranted to gain insight into the therapeutic potential of Gd-NCT.

Measurement of gamma-ray production from thermal neutron capture on gadolinium for neutrino experiments

NASA Astrophysics Data System (ADS)

Yano, Takatomi; 2012B0025 Collaboration; 2014B0126 Collaboration

2017-02-01

Recently, several scientific applications of gadolinium are found in neutrino physics experiments. Gadolinium-157 is the nucleus, which has the largest thermal neutron capture cross-section among all stable nuclei. Gadolinium-155 also has the large cross-section. These neutron capture reactions provide the gamma-ray cascade with the total energy of about 8 MeV. This reaction is applied for several neutrino experiments, e.g. reactor neutrino experiments and Gd doped large water Cherenkov detector experiments, to recognize inverse-beta-decay reaction. A good Gd(n,γ) simulation model is needed to evaluate the detection efficiency of the neutron capture reaction, i.e. the efficiency of IBD detection. In this presentation, we will report the development and study status of a Gd(n,γ) calculation model and comparison with our experimental data taken at ANNRI/MLF beam line, J-PARC.

Critical Questions Regarding Gadolinium Deposition in the Brain and Body After Injections of the Gadolinium-Based Contrast Agents, Safety, and Clinical Recommendations in Consideration of the EMA's Pharmacovigilance and Risk Assessment Committee Recommendation for Suspension of the Marketing Authorizations for 4 Linear Agents.

PubMed

Runge, Val M

2017-06-01

For magnetic resonance, the established class of intravenous contrast media is the gadolinium-based contrast agents. In the 3 decades since initial approval, these have proven in general to be very safe for human administration. However, in 2006, a devastating late adverse reaction to administration of the less stable gadolinium-based contrast agents was identified, nephrogenic systemic fibrosis. The result of actions taken by the European Medicines Agency and the US Food and Drug Administration, stratifying the agents by risk and contraindicating specific agents in severe renal dysfunction, has led to no new cases being identified in North America or Europe. Subsequently, in 2014, long-term deposition in the brain of gadolinium was first shown, after administration of 2 nonionic linear chelates, gadodiamide, and gadopentetate dimeglumine. This has led to an intense focus on the question of in vivo distribution, possible dechelation, and subsequent deposition of gadolinium, together with substantial clarification of the phenomenon as well as stratification of the agents on this basis. This review focuses on 8 critical questions regarding gadolinium deposition in the brain and body, with the answers and discussion therein important for future regulatory decisions and clinical practice. It is now clear that dechelation of gadolinium occurs in vivo with the linear agents and is responsible for this phenomenon, with key experts in the field recommending, except where there is no suitable alternative, a shift in clinical practice from the linear to macrocyclic agents. In addition, on March 10, 2017, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency recommended suspension of the marketing authorization for 4 linear gadolinium contrast agents-specifically Omniscan, Optimark, Magnevist, and MultiHance (gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadobenate dimeglumine)-for intravenous injection. Cited in the report was

Type-II domains in ferroelectric gadolinium molybdate (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bohm, J.; Kuersten, H.D.

Etching (001)-faces of gadolinium molybdate (GMO) reveals new kinds of domains. They are created by a translation, that leaves the spontaneous polarization and the transition parameter invariant. The translation vector is a part of a lattice vector, similar to stacking faults. (auth)

The Effect of Pressure and Temperature on Separation of Free Gadolinium(III) From Gd-DTPA Complex by Nanofiltration-Complexation Method

NASA Astrophysics Data System (ADS)

Rahayu, Iman; Anggraeni, Anni; Ukun, MSS; Bahti, Husein H.

2017-05-01

Nowdays, the utilization of rare earth elements has been carried out widely in industry and medicine, one of them is gadolinium in Gd-DTPA complex is used as a contrast agent in a magnetic resonance imaging (MRI) diagnostic to increase the visual contrast between normal tissue and diseased. Although the stability of a given complex may be high enough, the complexation step couldnot have been completed, so there is possible to gadolinium(III) in the complex compound. Therefore, the function of that compounds should be dangerous because of the toxicity of gadolinium(III) in human body. So, it is necessarry to separate free gadolinium(III) from Gd-DTPA complex by nanofiltration-complexation. The method of this study is complexing of Gd2O3 with DTPA ligand by reflux and separation of Gd-DTPA complex from gadolinium(III) with a nanofiltration membrane on the variation of pressures(2, 3, 4, 5, 6 bars) and temperature (25, 30, 35, 40 °C) and determined the flux and rejection. The results of this study are the higher of pressures and temperatures, permeation flux are increasing and ion rejections are decreasing and gave the free gadolinium(III) rejection until 86.26%.

Nanoamplifiers synthesized from gadolinium and gold nanocomposites for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Tian, Xiumei; Shao, Yuanzhi; He, Haoqiang; Liu, Huan; Shen, Yingying; Huang, Wenlin; Li, Li

2013-03-01

We have synthesized an efficient and highly sensitive nanoamplifier composed of gadolinium-doped silica nanoparticles and gold nanoparticles (AuNPs). Magnetic resonance imaging (MRI) in vitro and in vivo assays revealed enhancement of signal sensitivity, which may be explained by electron transfer between water and gadolinium-doped nanoparticles, apparent in the presence of gold. In vitro and in vivo evaluation demonstrated nanoamplifier incurred minimal cytotoxicity and immunotoxicity, increased stability, and gradual excretion patterns. Tumor targeted properties were preliminarily determined when the nanoamplifier was injected into mouse models of colon cancer liver metastasis. Furthermore, although AuNPs departed from the nanoamplifiers in specific mice tissues, optical and magnetic resonance imaging was efficient, especially in metastatic tumors. These assays validate our nanoamplifier as an effective MRI signal enhancer with sensitive cancer diagnosis potential.We have synthesized an efficient and highly sensitive nanoamplifier composed of gadolinium-doped silica nanoparticles and gold nanoparticles (AuNPs). Magnetic resonance imaging (MRI) in vitro and in vivo assays revealed enhancement of signal sensitivity, which may be explained by electron transfer between water and gadolinium-doped nanoparticles, apparent in the presence of gold. In vitro and in vivo evaluation demonstrated nanoamplifier incurred minimal cytotoxicity and immunotoxicity, increased stability, and gradual excretion patterns. Tumor targeted properties were preliminarily determined when the nanoamplifier was injected into mouse models of colon cancer liver metastasis. Furthermore, although AuNPs departed from the nanoamplifiers in specific mice tissues, optical and magnetic resonance imaging was efficient, especially in metastatic tumors. These assays validate our nanoamplifier as an effective MRI signal enhancer with sensitive cancer diagnosis potential. Electronic supplementary information

High Relaxivity Gadolinium Hydroxypyridonate-Viral Capsid Conjugates: Nano-sized MRI Contrast Agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meux, Susan C.; Datta, Ankona; Hooker, Jacob M.

2007-08-29

High relaxivity macromolecular contrast agents based on the conjugation of gadolinium chelates to the interior and exterior surfaces of MS2 viral capsids are assessed. The proton nuclear magnetic relaxation dispersion (NMRD) profiles of the conjugates show up to a five-fold increase in relaxivity, leading to a peak relaxivity (per Gd{sup 3+} ion) of 41.6 mM{sup -1}s{sup -1} at 30 MHz for the internally modified capsids. Modification of the exterior was achieved through conjugation to flexible lysines, while internal modification was accomplished by conjugation to relatively rigid tyrosines. Higher relaxivities were obtained for the internally modified capsids, showing that (1) theremore » is facile diffusion of water to the interior of capsids and (2) the rigidity of the linker attaching the complex to the macromolecule is important for obtaining high relaxivity enhancements. The viral capsid conjugated gadolinium hydroxypyridonate complexes appear to possess two inner-sphere water molecules (q = 2) and the NMRD fittings highlight the differences in the local motion for the internal ({tau}{sub RI} = 440 ps) and external ({tau}{sub RI} = 310 ps) conjugates. These results indicate that there are significant advantages of using the internal surface of the capsids for contrast agent attachment, leaving the exterior surface available for the installation of tissue targeting groups.« less

Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

PubMed Central

2010-01-01

Biocompatible poly-[N-(2-hydroxyethyl)-d,l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd. PMID:21170410

Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

NASA Astrophysics Data System (ADS)

Jeong, Sang Young; Kim, Hyo Jeong; Kwak, Byung-Kook; Lee, Ha-Young; Seong, Hasoo; Shin, Byung Cheol; Yuk, Soon Hong; Hwang, Sung-Joo; Cho, Sun Hang

2010-12-01

Biocompatible poly-[ N-(2-hydroxyethyl)- d, l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd.

Electron magnetic resonance investigation of gadolinium diffusion in zircon powders

NASA Astrophysics Data System (ADS)

de Biasi, R. S.; Grillo, M. L. N.

2011-11-01

The electron magnetic resonance (EMR) technique was used to investigate the diffusion of gadolinium in zircon (ZrSiO4) powders. The EMR absorption intensity was measured for several annealing times and three different temperatures of isothermal annealing: 1273, 1323 and 1373 K. The activation energy for diffusion, calculated from the experimental data using a theoretical model based on the Fick equation, was found to be EA=506±5 kJ mol-1. This value is close to the ones for the diffusion of Gd in UO2 and CeO2, but much larger than for the diffusion of gadolinium in a compound with the same crystal structure as zircon, YVO4. This is attributed to a difference in the relative sizes of the ions involved in the diffusion process.

Gadolinium concentration analysis in brain phantom by X-ray fluorescence.

PubMed

Almalki, Musaed; Majid, Samir Abdul; Butler, Philip H; Reinisch, Lou

2010-06-01

We have measured the X-ray fluorescence from gadolinium as a function of concentration and position in tumors of different sizes and shapes in a head phantom. The gadolinium fluorescence was excited with a 36 GBq Am-241 source. The fluorescence signal was detected with a CdTe detector and a multi-channel analyzer. The fluorescence peak was clearly separated from the scattered X-rays. Concentrations of 5.62-78.63 mg/ml of Gd ion were used in 1, 2, and 3 cm diameter spherical tumors and a 2x4 cm oblate spheroid tumor. The data show trends approaching saturation for the highest concentrations, probably due to reabsorption in the tumor. A comparison of X-ray photographic imaging and densitometer measurements to determine concentration is also presented.

Structural, kinetic, and thermodynamic characterization of the interconverting isomers of MS-325, a gadolinium(III)-based magnetic resonance angiography contrast agent.

PubMed

Tyeklar, Zoltan; Dunham, Stephen U; Midelfort, Katarina; Scott, Daniel M; Sajiki, Hirano; Ong, Karen; Lauffer, Randall B; Caravan, Peter; McMurry, Thomas J

2007-08-06

The amphiphilic gadolinium complex MS-325 ((trisodium-{(2-(R)-[(4,4-diphenylcyclohexyl) phosphonooxymethyl] diethylenetriaminepentaacetato) (aquo)gadolinium(III)}) is a contrast agent for magnetic resonance angiography (MRA). MS-325 comprises a GdDTPA core with an appended phosphodiester moiety linked to a diphenylcyclohexyl group to facilitate noncovalent binding to serum albumin and extension of the plasma half-life in vivo. The chiral DTPA ligand (R) was derived from L-serine, and upon complexation with gadolinium, forms two interconvertible diastereomers, denoted herein as isomers A and B. X-ray crystallography of the tris(ethylenediamine)cobalt(III) salt derivative of isomer A revealed a structure in the polar acentric space group P32. The structure consisted of three independent molecules of the gadolinium complex in the asymmetric unit along with three Delta-[Co(en)3]3+ cations, and it represents an unusual example of spontaneous Pasteur resolution of the cobalt cation. The geometry of the coordination core was best described as a distorted trigonal prism, and the final R factor was 5.6%. The configuration of the chiral central nitrogen of the DTPA core was S. The Gd-water (2.47-2.48 A), the Gd-acetate oxygens (2.34-2.42 A), and the Gd-N bond distances (central N, 2.59-2.63 A; terminal N, 2.74-2.80 A) were similar to other reported GdDTPA structures. The structurally characterized single crystal was one of two interconvertable diastereomers (isomers A and B) that equilibrated to a ratio of 1.81 to 1 at pH 7.4 and were separable at elevated pH by ion-exchange chromatography. The rate of isomerization was highly pH dependent: k1 = (1.45 +/- 0.08) x 102[H+] + (4.16 +/- 0.30) x 105[H+]2; k-1 = (2.57 +/- 0.17) x 102[H+] + (7.54 +/- 0.60) x 105[H+]2.

Recovery of methamphetamine associated cardiomyopathy predicted by late gadolinium enhanced cardiovascular magnetic resonance.

PubMed

Lopez, Javier E; Yeo, Khung; Caputo, Gary; Buonocore, Michael; Schaefer, Saul

2009-11-11

Methamphetamine is known to cause a cardiomyopathy which may be reversible with appropriate medical therapy and cessation of use. Late gadolinium enhancement cardiovascular magnetic resonance (CMR) has been shown to identify fibrosis in ischemic and non-ischemic cardiomyopathies. We present a case of severe methamphetamine-associated cardiomyopathy in which cardiac function recovered after 6 months. Evaluation by CMR using late gadolinium enhancement was notable for an absence of enhancement, suggesting an absence of irreversible myocyte injury and a good prognosis. CMR may be useful to predict recovery in toxin-associated non-ischemic cardiomyopathies.

Recovery of methamphetamine associated cardiomyopathy predicted by late gadolinium enhanced cardiovascular magnetic resonance

PubMed Central

2009-01-01

Methamphetamine is known to cause a cardiomyopathy which may be reversible with appropriate medical therapy and cessation of use. Late gadolinium enhancement cardiovascular magnetic resonance (CMR) has been shown to identify fibrosis in ischemic and non-ischemic cardiomyopathies. We present a case of severe methamphetamine-associated cardiomyopathy in which cardiac function recovered after 6 months. Evaluation by CMR using late gadolinium enhancement was notable for an absence of enhancement, suggesting an absence of irreversible myocyte injury and a good prognosis. CMR may be useful to predict recovery in toxin-associated non-ischemic cardiomyopathies. PMID:19906310

Acute side effects of three commonly used gadolinium contrast agents in the paediatric population.

PubMed

Neeley, Chris; Moritz, Michael; Brown, Jeffrey J; Zhou, Yihua

2016-07-01

To determine the incidence of acute side effects of three commonly used gadolinium contrast agents in the paediatric population. A retrospective review of medical records was performed to determine the incidence of acute adverse side effects of i.v. gadolinium contrast agents [MultiHance(®) (Bracco Diagnostics Inc., Princeton, NJ), Magnevist(®) (Bayer Healthcare Pharmaceuticals, Wayne, NJ) or Gadavist(®) (Bayer HealthCare Pharmaceuticals)] in paediatric patients. 40 of the 2393 patients who received gadolinium contrast agents experienced acute side effects, representing an incidence of 1.7%. The majority of the acute side effects (in 30 patients) were nausea and vomiting. The incidence was significantly higher in non-sedated patients (2.37% vs 0.7%; p = 0.0018). Furthermore, without sedation, the incidence of both nausea and vomiting was significantly higher in children receiving MultiHance, with a 4.48% incidence of nausea when compared with Magnevist (0.33%, p < 0.0001) and Gadavist (0.28%, p < 0.0001) and a 2.36% incidence of vomiting compared with those for Magnevist (0.50%, p = 0.0054) and Gadavist (0.28%, p = 0.014), whereas no difference was observed between Magnevist and Gadavist within the power of the study. In addition, there was no apparent difference between any of the three contrast agents for the incidence of allergy or other acute side effects detected, given the sample size. The gadolinium contrast agents MultiHance, Magnevist and Gadavist have a low incidence of acute side effects in the paediatric population, a rate that is further reduced in moderately sedated patients. MultiHance demonstrated significantly increased incidence of gastrointestinal symptoms compared with Magnevist and Gadavist. The incidence of acute side effects of three commonly used gadolinium contrast agents was determined in the paediatric population, which can have clinical implications.

Layered gadolinium hydroxides for low-temperature magnetic cooling.

PubMed

Abellán, Gonzalo; Espallargas, Guillermo Mínguez; Lorusso, Giulia; Evangelisti, Marco; Coronado, Eugenio

2015-09-28

Layered gadolinium hydroxides have revealed to be excellent candidates for cryogenic magnetic refrigeration. These materials behave as pure 2D magnetic systems with a Heisenberg-Ising critical crossover, induced by dipolar interactions. This 2D character and the possibility offered by these materials to be delaminated open the possibility of rapid heat dissipation upon substrate deposition.

Gadolinium-148 and other spallation production cross section measurements for accelerator target facilities

NASA Astrophysics Data System (ADS)

Kelley, Karen Corzine

At the Los Alamos Neutron Science Center accelerator complex, protons are accelerated to 800 MeV and directed to two tungsten targets, Target 4 at the Weapons Neutron Research facility and the 1L target at the Lujan Center. The Department of Energy requires hazard classification analyses to be performed on these targets and places limits on certain radionuclide inventories in the targets to avoid characterizing the facilities as "nuclear facilities." Gadolinium-148 is a radionuclide created from the spallation of tungsten. Allowed isotopic inventories are particularly low for this isotope because it is an alpha-particle emitter with a 75-year half-life. The activity level of Gadolinium-148 is low, but it encompasses almost two-thirds of the total dose burden for the two tungsten targets based on present yield estimates. From a hazard classification standpoint, this severely limits the lifetime of these tungsten targets. The cross section is not well-established experimentally and this is the motivation for measuring the Gadolinium-148 production cross section from tungsten. In a series of experiments at the Weapons Neutron Research facility, Gadolinium-148 production was measured for 600- and 800-MeV protons on tungsten, tantalum, and gold. These experiments used 3 mum thin tungsten, tantalum, and gold foils and 10 mum thin aluminum activation foils. In addition, spallation yields were determined for many short-lived and long-lived spallation products with these foils using gamma and alpha spectroscopy and compared with predictions of the Los Alamos National Laboratory codes CEM2k+GEM2 and MCNPX. The cumulative Gadolinium-148 production cross section measured from tantalum, tungsten, and gold for incident 600-MeV protons were 15.2 +/- 4.0, 8.31 +/- 0.92, and 0.591 +/- 0.155, respectively. The average production cross sections measured at 800 MeV were 28.6 +/- 3.5, 19.4 +/- 1.8, and 3.69 +/- 0.50 for tantalum, tungsten, and gold, respectively. These cumulative

Characterization of PAH matrix with monazite stream containing uranium, gadolinium and iron

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pal, Sangita, E-mail: sangpal@barc.gov.in; Goswami, D.; Meena, Sher Singh

2016-05-23

Uranium (U) gadolinium (Gd) and iron (Fe) containing alkaline waste simulated effluent (relevant to alkaline effluent of monazite ore) has been treated with a novel amphoteric resin viz, Polyamidehydroxamate (PAH) containing amide and hydroxamic acid groups. The resin has been synthesized in an eco-friendly manner by polymerization nad conversion to functional groups characterized by FT-IR spectra and architectural overview by SEM. Coloration of the loaded matrix and de-coloration after extraction of uranium is the special characteristic of the matrix. Effluent streams have been analyzed by ICP-AES, U loaded PAH has been characterized by FT-IR, EXAFS, Gd and Fe by X-raymore » energy values of EDXRF at 6.053 KeVand 6.405 KeV respectively. The remarkable change has been observed in Mössbauer spectrum of Fe-loaded PAH samples.« less

The network formers role of gadolinium(III) ions in some zinc-borate glass ceramics

NASA Astrophysics Data System (ADS)

Bosca, Maria; Pop, Lidia; Pascuta, Petru

2017-12-01

EPR and magnetic susceptibility measurements were performed on glass ceramics from the (Gd2O3)x.(B2O3)(60-x).(ZnO)40 system, with 0 ≤ x ≤ 15 mol%, in order to determine the role of gadolinium ions on structural and magnetic properties. At low Gd2O3 contents (x ≤ 1 mol%) the EPR spectra show four resonance lines with effective g-values of ˜ 6, 4.8, 2.8 and 2, typical for Gd3+ ions uniformly distributed in the glass and glass ceramic samples. For higher contents of gadolinium ions (x ≥ 3 mol%) the EPR spectra are dominated by a single broad line centered at g ˜ 2, which can be due to the magnetic clusters containing Gd3+ ions. The magnetic susceptibility data show that the gadolinium ions are involved in superexchange interactions in all the investigated glass ceramics, being antiferromagnetically coupled.

MO-FG-BRA-07: Theranostic Gadolinium-Based AGuIX Nanoparticles for MRI-Guided Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Detappe, A; Institut Lumiere-Matiere, Villeurbanne; Nano-H, St-Quentin Fallavier

2015-06-15

Purpose: AGuIX are gadolinium-based nanoparticles, initially developed for MRI, that have a potential role in radiation therapy as a radiosensitizer. Our goal is to demonstrate that these nanoparticles can both be used as an MRI contrast agent, as well as to obtain local dose enhancement in a pancreatic tumor when delivered in combination with an external beam irradiation. Methods: We performed in vitro cell uptake and radiosensitization studies of a pancreatic cancer cell line in a low energy (220kVp) beam, a standard clinical 6MV beam (STD) and a flattening filter free clinical 6MV beam (FFF). After injection of 40mM ofmore » nanoparticles, a biodistribution study was performed in vivo on mice with subcutaneous xenograft pancreatic tumors. In vivo radiation therapy studies were performed at the time point of maximum tumor uptake. Results: The concentration of AGuIX nanoparticles in Panc-1 pancreatic cancer cells, determined in vitro by MRI and ICPMS, peaks after 30 minutes with 0.3% of the initial concentration (5mg/g). Clonogenic assays show a significant effect (p<0.05) when the AGuIX are coupled with MV photon irradiation (DEF20%=1.31). Similar AGuIX tumor uptake is found in vivo by both MRI and ICPMS 30 minutes after intravenous injection. For long term survival studies, the choice of the radiation dose is determined with 5 control groups (3mice/group) irradiated with 0, 5, 10, 15, and 20Gy. Afterwards, 4 groups (8mice/group) are used to evaluate the effect of the nanoparticles. A Logrank test is performed as a statistical test to evaluate the effect of the nanoparticles. Conclusion: The combination of the MRI contrast and radiosensitization properties of gadolinium nanoparticles reveals a strong potential for usage with MRI-guided radiation therapy.« less

Sensitive and transportable gadolinium-core plastic scintillator sphere for neutron detection and counting

NASA Astrophysics Data System (ADS)

Dumazert, Jonathan; Coulon, Romain; Carrel, Frédérick; Corre, Gwenolé; Normand, Stéphane; Méchin, Laurence; Hamel, Matthieu

2016-08-01

Neutron detection forms a critical branch of nuclear-related issues, currently driven by the search for competitive alternative technologies to neutron counters based on the helium-3 isotope. The deployment of plastic scintillators shows a high potential for efficient detectors, safer and more reliable than liquids, more easily scalable and cost-effective than inorganic. In the meantime, natural gadolinium, through its 155 and mostly 157 isotopes, presents an exceptionally high interaction probability with thermal neutrons. This paper introduces a dual system including a metal gadolinium core inserted at the center of a high-scale plastic scintillator sphere. Incident fast neutrons are thermalized by the scintillator shell and then may be captured with a significant probability by gadolinium 155 and 157 nuclei in the core. The deposition of a sufficient fraction of the capture high-energy prompt gamma signature inside the scintillator shell will then allow discrimination from background radiations by energy threshold, and therefore neutron detection. The scaling of the system with the Monte Carlo MCNPX2.7 code was carried out according to a tradeoff between the moderation of incident fast neutrons and the probability of slow neutron capture by a moderate-cost metal gadolinium core. Based on the parameters extracted from simulation, a first laboratory prototype for the assessment of the detection method principle has been synthetized. The robustness and sensitivity of the neutron detection principle are then assessed by counting measurement experiments. Experimental results confirm the potential for a stable, highly sensitive, transportable and cost-efficient neutron detector and orientate future investigation toward promising axes.

T1 relaxivity of core-encapsulated gadolinium liposomal contrast agents--effect of liposome size and internal gadolinium concentration.

PubMed

Ghaghada, Ketan; Hawley, Catherine; Kawaji, Keigo; Annapragada, Ananth; Mukundan, Srinivasan

2008-10-01

Long circulating core-encapsulated gadolinium (CE-Gd) liposomal nanoparticles that have surface conjugated polyethylene glycol are a promising platform technology for use as blood pool T1-based magnetic resonance (MR) contrast agents. The objective of this study was to investigate the effect of liposome size and internal (core) Gd concentration on the T1 relaxivity of CE-Gd liposomes. Twelve different liposomal formulations were synthesized and characterized, resulting in a size (50, 100, 200, and 400 nm) and core Gd-concentration (200, 350, and 500 mM) "matrix" of test samples. Subsequently, CE-Gd liposomes were diluted in deionized water (four diluted samples) and molar T1 relaxivity (r1) measurements were performed at 2- and 7-T MR field strengths. The r1 of CE-Gd liposomes was inversely related to the liposome size. The largest change in r1 was observed between liposomes that were extruded through 50- and 100-nm filter membranes. At both field strengths, the variation in internal gadolinium concentration did not show any significant correlation (alpha < or = 0.05) with r1. The size of CE-Gd liposomal nanoparticles significantly affects the T1 relaxivity. An inverse relation was observed between liposome size and T1 relaxivity. The T1 relaxivity did not change significantly with core Gd concentration over the measured concentration range.

Magnetization reversal and inverted magnetoresistance of exchange-biased spin valves with a gadolinium layer

NASA Astrophysics Data System (ADS)

Milyaev, M.; Naumova, L.; Chernyshova, T.; Proglyado, V.; Kamensky, I.; Krinitsina, T.; Ryabukhina, M.; Ustinov, V.

2017-03-01

FeMn-based spin valves with a gadolinium layer have been fabricated by magnetron sputtering. The magnetoresistive properties of the spin valves have been investigated at temperatures of 80-293 K. Temperature-induced switching between low- and high-resistance magnetic states has been revealed. Realization of the low- or high-resistance states depends on which magnetic moment dominates in the exchange-coupled Gd/CoFe, of Gd or CoFe. It has been shown that the switching temperature depends on the thickness of the gadolinium layer.

Gadolinium-based nanoparticles for highly efficient T1-weighted magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Lim, Eun-Kyung; Kang, Byunghoon; Choi, Yuna; Jang, Eunji; Han, Seungmin; Lee, Kwangyeol; Suh, Jin-Suck; Haam, Seungjoo; Huh, Yong-Min

2014-06-01

We developed Pyrene-Gadolinium (Py-Gd) nanoparticles as pH-sensitive magnetic resonance imaging (MRI) contrast agents capable of showing a high-Mr signal in cancer-specific environments, such as acidic conditions. Py-Gd nanoparticles were prepared by coating Py-Gd, which is a complex of gadolinium with pyrenyl molecules, with pyrenyl polyethyleneglycol PEG using a nano-emulsion method. These particles show better longitudinal relaxation time (T1) MR signals in acidic conditions than they do in neutral conditions. Furthermore, the particles exhibit biocompatibility and MR contrast effects in both in vitro and in vivo studies. From these results, we confirm that Py-Gd nanoparticles have the potential to be applied for accurate cancer diagnosis and therapy.

Characterization of the reaction products and precipitates at the interface of carbon fiber reinforced magnesium–gadolinium composite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yaping; Jiang, Longtao, E-mail: longtaojiang@163.com; Chen, Guoqin

2016-03-15

In the present work, carbon fiber reinforced magnesium-gadolinium composite was fabricated by pressure infiltration method. The phase composition, micro-morphology, and crystal structure of reaction products and precipitates at the interface of the composite were investigated. Scanning electron microscopy and energy dispersive spectroscopy analysis revealed the segregation of gadolinium element at the interface between carbon fiber and matrix alloy. It was shown that block-shaped Gd4C5, GdC2 and nano-sized Gd2O3 were formed at the interface during the fabrication process due to the interfacial reaction. Furthermore, magnesium-gadolinium precipitates including needle-like Mg5Gd (or Mg24Gd5) and thin plate-shaped long period stacking-ordered phase, were also observedmore » at the interface and in the matrix near the interface. The interfacial microstructure and bonding mode were influenced by these interfacial products, which were beneficial for the improvement of the interfacial bonding strength. - Highlights: • Gadolinium element segregated on the surface of carbon fibers. • Block-shaped Gd{sub 4}C{sub 5} and GdC{sub 2} were formed at the interface via chemical reaction. • Gadolinium and oxygen reacted at the interface and formed nano-scaled Gd{sub 2}O{sub 3}. • The precipitates formed in the interface were identified to be Mg{sub 5}Gd (or Mg{sub 24}Gd{sub 5}) and plate-shaped long period stacking-ordered phase.« less

Simple method for quantification of gadolinium magnetic resonance imaging contrast agents using ESR spectroscopy.

PubMed

Takeshita, Keizo; Kinoshita, Shota; Okazaki, Shoko

2012-01-01

To develop an estimation method of gadolinium magnetic resonance imaging (MRI) contrast agents, the effect of concentration of Gd compounds on the ESR spectrum of nitroxyl radical was examined. A solution of either 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPONE) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) was mixed with a solution of Gd compound and the ESR spectrum was recorded. Increased concentration of gadolinium-diethylenetriamine pentaacetic acid chelate (Gd-DTPA), an MRI contrast agent, increased the peak-to-peak line widths of ESR spectra of the nitroxyl radicals, in accordance with a decrease of their signal heights. A linear relationship was observed between concentration of Gd-DTPA and line width of ESR signal, up to approximately 50 mmol/L Gd-DTPA, with a high correlation coefficient. Response of TEMPONE was 1.4-times higher than that of TEMPOL as evaluated from the slopes of the lines. The response was slightly different among Gd compounds; the slopes of calibration curves for acua[N,N-bis[2-[(carboxymethyl)[(methylcarbamoyl)methyl]amino]ethyl]glycinato(3-)]gadolinium hydrate (Gd-DTPA-BMA) (6.22 μT·L/mmol) and gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid chelate (Gd-DOTA) (6.62 μT·L/mmol) were steeper than the slope for Gd-DTPA (5.45 μT·L/mmol), whereas the slope for gadolinium chloride (4.94 μT·L/mmol) was less steep than that for Gd-DTPA. This method is simple to apply. The results indicate that this method is useful for rough estimation of the concentration of Gd contrast agents if calibration is carried out with each standard compound. It was also found that the plot of the reciprocal square root of signal height against concentrations of contrast agents could be useful for the estimation if a constant volume of sample solution is taken and measured at the same position in the ESR cavity every time.

Nephrogenic systemic fibrosis (NSF): a late adverse reaction to some of the gadolinium based contrast agents

PubMed Central

Marckmann, Peter; Logager, Vibeke B.

2007-01-01

Abstract Until recently it was believed that extracellular gadolinium based contrast agents were safe for both the kidneys and all other organs within the dose range up to 0.3 mmol/kg body weight. However, in 2006, it was demonstrated that some gadolinium based contrast agents may trigger the development of nephrogenic systemic fibrosis, a generalised fibrotic disorder, in renal failure patients. Accordingly, the use of gadodiamide and gadopentate dimeglumine for renal failure patients was banned in Europe in spring 2007. The same two compounds should only be used cautiously in patients with moderate renal dysfunction. The current paper reviews the situation (July 2007) regarding gadolinium based contrast agent and the severe delayed reaction to some of these agents. The fear of nephrogenic systemic fibrosis should not lead to a denial of a well indicated enhanced magnetic resonance imaging examination. PMID:17905680

Measurement of gadolinium retention: current status and review from an applied radiation physics perspective.

PubMed

Gräfe, James L; McNeill, Fiona E

2018-06-28

This article briefly reviews the main measurement techniques for the non-invasive detection of residual gadolinium (Gd) in those exposed to gadolinium-based contrast agents (GBCAs). Approach and Main results: The current status of in vivo Gd measurement is discussed and is put into the context of concerns within the radiology community. The main techniques are based on applied atomic/nuclear medicine utilizing the characteristic atomic and nuclear spectroscopic signature of Gd. The main emission energies are in the 40-200 keV region and require spectroscopic detectors with good energy resolution. The two main techniques, prompt gamma neutron activation analysis and x-ray fluorescence, provide adequate detection limits for in vivo measurement, whilst delivering a low effective radiation dose on the order of a few µSv. Gadolinium is being detected in measureable quantities in people with healthy renal function who have received FDA approved GBCAs. The applied atomic/nuclear medicine techniques discussed in this review will be useful in determining the significance of this retention, and will help on advising future administration protocols.

Process factors facilitating and inhibiting medical ethics teaching in small groups.

PubMed

Bentwich, Miriam Ethel; Bokek-Cohen, Ya'arit

2017-11-01

To examine process factors that either facilitate or inhibit learning medical ethics during case-based learning. A qualitative research approach using microanalysis of transcribed videotaped discussions of three consecutive small-group learning (SGL) sessions on medical ethics teaching (MET) for three groups, each with 10 students. This research effort revealed 12 themes of learning strategies, divided into 6 coping and 6 evasive strategies. Cognitive-based strategies were found to relate to Kamin's model of critical thinking in medical education, thereby supporting our distinction between the themes of coping and evasive strategies. The findings also showed that cognitive efforts as well as emotional strategies are involved in discussions of ethical dilemmas. Based on Kamin's model and the constructivist learning theory, an examination of the different themes within the two learning strategies-coping and evasive-revealed that these strategies may be understood as corresponding to process factors either facilitating or inhibiting MET in SGL, respectively. Our classification offers a more nuanced observation, specifically geared to pinpointing the desired and less desired process factors in the learning involved in MET in the SGL environment. Two key advantages of this observation are: (1) it brings to the forefront process factors that may inhibit and not merely facilitate MET in SGL and (2) it acknowledges the existence of emotional and not just cognitive process factors. Further enhancement of MET in SGL may thus be achieved based on these observations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The evolution of gadolinium based contrast agents: from single-modality to multi-modality

NASA Astrophysics Data System (ADS)

Zhang, Li; Liu, Ruiqing; Peng, Hui; Li, Penghui; Xu, Zushun; Whittaker, Andrew K.

2016-05-01

Gadolinium-based contrast agents are extensively used as magnetic resonance imaging (MRI) contrast agents due to their outstanding signal enhancement and ease of chemical modification. However, it is increasingly recognized that information obtained from single modal molecular imaging cannot satisfy the higher requirements on the efficiency and accuracy for clinical diagnosis and medical research, due to its limitation and default rooted in single molecular imaging technique itself. To compensate for the deficiencies of single function magnetic resonance imaging contrast agents, the combination of multi-modality imaging has turned to be the research hotpot in recent years. This review presents an overview on the recent developments of the functionalization of gadolinium-based contrast agents, and their application in biomedicine applications.

Helium defectoscopy of cerium gadolinium ceramics Ce0.8Gd0.2O1.9 with a submicrocrystalline structure in the impurity disorder region

NASA Astrophysics Data System (ADS)

Koromyslov, A. V.; Zhiganov, A. N.; Kovalenko, M. A.; Kupryazhkin, A. Ya.

2013-12-01

The concentration of impurity anion vacancies formed upon the dissociation of gadolinium-vacancy complexes has been determined using helium defectoscopy of the cerium gadolinium ceramics Ce0.8Gd0.2O1.9 with a submicrocrystalline structure in the temperature range T = 740-1123 K and at saturation pressures ranging from 0.05 to 15 MPa. It has been found that the energy of dissociation of gadoliniumvacancy complexes is E {eff/ D }= 0.26 ± 0.06 eV, and the energy of dissolution of helium in anion vacancies in the impurity disorder region is E P = -0.31 ± 0.09 eV. The proposed mechanism of dissolution has been confirmed by the investigation of the electrical conductivity of the cerium gadolinium ceramics, as well as by the high-speed molecular dynamics simulation of the dissociation of gadolinium-vacancy complexes. It has been assumed that a decrease in the effective dissolution energy in comparison with the results of the previously performed low-temperature investigations is caused by the mutual repulsion of vacancies formed upon the dissociation of gadolinium-vacancy complexes in highly concentrated solutions of gadolinium in CeO2 with increasing temperature.

Light deflection in gadolinium molybdate ferroelastic crystals

NASA Astrophysics Data System (ADS)

Staniorowski, Piotr; Bornarel, Jean

2000-02-01

The deflection of a He-Ne light beam by polydomain gadolinium molybdate (GMO) crystals has been studied with respect to incidence angle icons/Journals/Common/alpha" ALT="alpha" ALIGN="TOP"/> i on the sample at room temperature. The A and B deflected beams do not cross each other during the icons/Journals/Common/alpha" ALT="alpha" ALIGN="TOP"/> i variation, in contrast to results and calculations previously published. The model using the Fresnel equation confirms this result. The model presented is more accurate for numerical calculation than that using the Huygens construction.

Impact of the Glymphatic System on the Kinetic and Distribution of Gadodiamide in the Rat Brain: Observations by Dynamic MRI and Effect of Circadian Rhythm on Tissue Gadolinium Concentrations.

PubMed

Taoka, Toshiaki; Jost, Gregor; Frenzel, Thomas; Naganawa, Shinji; Pietsch, Hubertus

2018-04-12

The glymphatic system is a recently hypothesized waste clearance system of the brain in which perivascular space constitutes a pathway similar to the lymphatic system in other body regions. Sleep and anesthesia are reported to influence the activity of the glymphatic system. Because rats are nocturnal animals, the glymphatic system is expected to be more active during the day. We attempted to elucidate the influence of the glymphatic system for intravenously injected gadodiamide in the rat brain by 2 experiments. One was a magnetic resonance imaging (MRI) experiment to evaluate the short-term dynamics of signal intensity changes after gadodiamide administration. The other was a quantification experiment to evaluate the concentration of retained gadolinium within the rat brain after repeated intravenous administration of gadodiamide at different times of day and levels of anesthesia. The imaging experiment was performed on 6 rats that received an intravenous injection of gadodiamide (1 mmol/kg) and dynamic MRI for 3 hours at 2.4-minute intervals. The time course of the signal intensity changes was evaluated for different brain structures. The tissue quantification experiment was performed on 24 rats divided into 4 groups by injection time (morning, late afternoon) and anesthesia (none, short, long) during administration. All animals received gadodiamide (1.8 mmol/kg, 8 times over 2 weeks). Gadolinium concentration of dissected brain tissues was quantified 5 weeks after the last administration by inductively coupled plasma mass spectrometry. In the imaging experiment, muscle and the fourth ventricle showed an instantaneous signal intensity increase immediately after gadodiamide injection. The signal curve of the cerebral cortex and deep cerebellar nuclei reached the peak signal intensity later than the fourth ventricle but earlier than that of the prepontine cistern. In the gadolinium quantification experiment, the concentration in the group with the morning

Ferromagnetic coupling in the three-dimensional malonato-bridged gadoliniumIII complex [Gd2(mal)3(H2O)6] (H2mal = malonic acid).

PubMed

Hernández-Molina, María; Ruiz-Pérez, Catalina; López, Trinidad; Lloret, Francesc; Julve, Miguel

2003-09-08

The novel gadolinium(III) complex of formula [Gd(2)(mal)(3)(H(2)O)(6)] (1) (H(2)mal = 1,3-propanedioic acid) has been prepared and characterized by X-ray diffraction analysis. Crystal data for 1: monoclinic, space group I2/a, a = 11.1064(10) A, b = 12.2524(10) A, c =13.6098(2) A, beta = 92.925(10) degrees, U = 1849.5(3) A(3), Z = 4. Compound 1 is a three-dimensional network made up of malonate-bridged gadolinium(III) ions where the malonate exhibits two bridging modes, eta(5)-bidentate + unidentate and eta(3):eta(3) + bis(unidentate). The gadolinium atom is nine-coordinate with three water molecules and six malonate oxygen atoms from three malonate ligands forming a distorted monocapped square antiprism. The shortest metal-metal separations are 4.2763(3) A [through the oxo-carboxylate bridge] and 6.541(3) A [through the carboxylate in the anti-syn coordination mode]. The value of the angle at the oxo-carboxylate atom is 116.8(2) degrees. Variable-temperature magnetic susceptibility measurements reveal the occurrence of a significant ferromagnetic interaction through the oxo-carboxylate pathway (J = +0.048(1) cm(-1), H = -JS(Gd(1)) x S(Gd(1a))).

Computational exploration of zinc binding groups for HDAC inhibition.

PubMed

Chen, Kai; Xu, Liping; Wiest, Olaf

2013-05-17

Histone deacetylases (HDACs) have emerged as important drug targets in epigenetics. The most common HDAC inhibitors use hydroxamic acids as zinc binding groups despite unfavorable pharmacokinetic properties. A two-stage protocol of M05-2X calculations of a library of 48 fragments in a small model active site, followed by QM/MM hybrid calculations of the full enzyme with selected binders, is used to prospectively select potential bidentate zinc binders. The energetics and interaction patterns of several zinc binders not previously used for the inhibition of HDACs are discussed.

Effects of exposure to gadolinium on the development of geographically and phylogenetically distant sea urchins species.

PubMed

Martino, Chiara; Bonaventura, Rosa; Byrne, Maria; Roccheri, Maria; Matranga, Valeria

2017-07-01

Gadolinium (Gd), a metal of the lanthanide series used as contrast agent for magnetic resonance imaging, is released into the aquatic environment. We investigated the effects of Gd on the development of four sea urchin species: two from Europe, Paracentrotus lividus and Arbacia lixula, and two from Australia, Heliocidaris tuberculata and Centrostephanus rodgersii. Exposure to Gd from fertilization resulted in inhibition or alteration of skeleton growth in the plutei. The similar morphological response to Gd in the four species indicates a similar mechanism underlying abnormal skeletogenesis. Sensitivity to Gd greatly varied, with the EC50 ranging from 56 nM to 132 μM across the four species. These different sensitivities highlight the importance of testing toxicity in several species for risk assessment. The strong negative effects of Gd on calcification in plutei, together with the plethora of marine species that have calcifying larvae, indicates that Gd pollution is urgent issue that needs to be addressed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Progressing Toward a Cohesive Pediatric 18F-FDG PET/MR Protocol: Is Administration of Gadolinium Chelates Necessary?

PubMed

Klenk, Christopher; Gawande, Rakhee; Tran, Vy Thao; Leung, Jennifer Trinh; Chi, Kevin; Owen, Daniel; Luna-Fineman, Sandra; Sakamoto, Kathleen M; McMillan, Alex; Quon, Andy; Daldrup-Link, Heike E

2016-01-01

With the increasing availability of integrated PET/MR scanners, the utility and need for MR contrast agents for combined scans is questioned. The purpose of our study was to evaluate whether administration of gadolinium chelates is necessary for evaluation of pediatric tumors on (18)F-FDG PET/MR images. First, in 119 pediatric patients with primary and secondary tumors, we used 14 diagnostic criteria to compare the accuracy of several MR sequences: unenhanced T2-weighted fast spin-echo imaging; unenhanced diffusion-weighted imaging; and-before and after gadolinium chelate contrast enhancement-T1-weighted 3-dimensional spoiled gradient echo LAVA (liver acquisition with volume acquisition) imaging. Next, in a subset of 36 patients who had undergone (18)F-FDG PET within 3 wk of MRI, we fused the PET images with the unenhanced T2-weighted MR images (unenhanced (18)F-FDG PET/MRI) and the enhanced T1-weighted MR images (enhanced (18)F-FDG PET/MRI). Using the McNemar test, we compared the accuracy of the two types of fused images using the 14 diagnostic criteria. We also evaluated the concordance between (18)F-FDG avidity and gadolinium chelate enhancement. The standard of reference was histopathologic results, surgical notes, and follow-up imaging. There was no significant difference in diagnostic accuracy between the unenhanced and enhanced MR images. Accordingly, there was no significant difference in diagnostic accuracy between the unenhanced and enhanced (18)F-FDG PET/MR images. (18)F-FDG avidity and gadolinium chelate enhancement were concordant in 30 of the 36 patients and 106 of their 123 tumors. Gadolinium chelate administration is not necessary for accurate diagnostic characterization of most solid pediatric malignancies on (18)F-FDG PET/MR images, with the possible exception of focal liver lesions. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Study of the Photon Strength Functions for Gadolinium Isotopes with the DANCE Array

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dashdorj, D.; Mitchell, G. E.; Baramsai, B.

2009-03-10

The gadolinium isotopes are interesting for reactor applications as well as for medicine and astrophysics. The gadolinium isotopes have some of the largest neutron capture cross sections. As a consequence they are used in the control rod in reactor fuel assembly. From the basic science point of view, there are seven stable isotopes of gadolinium with varying degrees of deformation. Therefore they provide a good testing ground for the study of deformation dependent structure such as the scissors mode. Decay gamma rays following neutron capture on Gd isotopes are detected by the DANCE array, which is located at flight pathmore » 14 at the Lujan Neutron Scattering Center at Los Alamos National Laboratory. The high segmentation and close packing of the detector array enable gamma-ray multiplicity measurements. The calorimetric properties of the DANCE array coupled with the neutron time-of-flight technique enables one to gate on a specific resonance of a specific isotope in the time-of-flight spectrum and obtain the summed energy spectrum for that isotope. The singles gamma-ray spectrum for each multiplicity can be separated by their DANCE cluster multiplicity. Various photon strength function models are used for comparison with experimentally measured DANCE data and provide insight for understanding the statistical decay properties of deformed nuclei.« less

Tissue gadolinium deposition in renally impaired rats exposed to different gadolinium-based MRI contrast agents: evaluation with inductively coupled plasma mass spectrometry (ICP-MS).

PubMed

Sato, Tomohiro; Ito, Katsuyoshi; Tamada, Tsutomu; Kanki, Akihiko; Watanabe, Shigeru; Nishimura, Hirotake; Tanimoto, Daigo; Higashi, Hiroki; Yamamoto, Akira

2013-10-01

To quantify tissue gadolinium (Gd) deposition in renally impaired rats exposed to Gd-EOB-DTPA and other Gd-based MRI contrast agents by means of inductively coupled plasma mass spectrometry (ICP-MS), and to compare the differences in distribution among major organs as possible triggers for nephrogenic systemic fibrosis (NSF). A total of 15 renally impaired rats were injected with Gd-EOB-DTPA, Gd-DTPA-BMA and Gd-HP-DO3A. Gd contents of skin, liver, kidney, lung, heart, spleen, diaphragm and femoral muscle were measured by inductively coupled plasma mass spectrometry (ICP-MS). Histological assessment was also conducted. Tissue Gd deposition in all organs was significantly higher (P=0.005~0.009) in the Gd-DTPA-BMA group than in the Gd-HP-DO3A and Gd-EOB-DTPA groups. In the Gd-DTPA-BMA group, Gd was predominantly deposited in kidney (1306±605.7μg/g), followed by skin, liver, lung, spleen, femoral muscle, diaphragm and heart. Comparing Gd-HP-DO3A and Gd-EOB-DTPA groups, Gd depositions in the kidney, liver and lung were significantly lower (P=0.009~0.011) in the Gd-EOB-DTPA group than in the Gd-HP-DO3A group although no significant differences were seen for any other organs. Gd-EOB-DTPA is a stable and safe Gd-based contrast agent (GBCA) showing lower Gd deposition in major organs in renally impaired rats, compared with other GBCAs. This fact suggests that the risk of NSF onset would be low in the use of Gd-EOB-DTPA. Copyright © 2013 Elsevier Inc. All rights reserved.

Kinetic characteristics of the luminescence decay for industrial yttrium-gadolinium-aluminium garnet based phosphors

NASA Astrophysics Data System (ADS)

Lisitsyn, V. M.; Stepanov, S. A.; Valiev, D. T.; Vishnyakova, E. A.; Abdullin, H. A.; Marhabaeva, A. A.; Tulegenova, A. T.

2016-02-01

The spectral and decay kinetic characteristics of pulse cathodoluminescence and photoluminescence of phosphors based on yttrium-gadolinium-aluminum garnet were investigated using pulsed optical time resolved spectroscopy.

Geometrically confined ultrasmall gadolinium oxide nanoparticles boost the T1 contrast ability

NASA Astrophysics Data System (ADS)

Ni, Kaiyuan; Zhao, Zhenghuan; Zhang, Zongjun; Zhou, Zijian; Yang, Li; Wang, Lirong; Ai, Hua; Gao, Jinhao

2016-02-01

High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon-Bloembergen-Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM-1 s-1. Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy provides new guidance for developing various high-performance T1 contrast agents for sensitive imaging and disease diagnosis.High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon-Bloembergen-Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM-1 s-1. Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy

MRI of normal and abnormal duodenum using Half-Fourier Single-Shot RARE and gadolinium-enhanced spoiled gradient echo sequences.

PubMed

Marcos, H B; Semelka, R C; Noone, T C; Woosley, J T; Lee, J K

1999-07-01

The objective of this research was two-fold: First, to describe the normal and abnormal MR appearances of the duodenum using combined Half-Fourier Acquisition Single Shot RARE (HASTE) and gadolinium-enhanced standard and fat suppressed spoiled gradient echo (SGE) sequences. The second objective was to assess the ability of these combined sequences to detect and characterize duodenal diseases. MR examinations were performed on fifty consecutive patients with no clinical history of duodenal diseases, who were 1) imaged with HASTE and gadolinium-enhanced standard and fat suppressed SGE sequences and 2) referred to MR examination for reasons other than duodenal diseases, and were reviewed retrospectively to determine the normal MR appearances of the duodenum. A second population of patients with abnormal duodenum who were imaged with the same MR sequences were included in the second part of this study. This population was composed of 20 consecutive patients with subsequently proven duodenal abnormalities, including: malrotation (2), diverticula (4), intussusception (1), sprue (1), polyps (2), neurofibroma (1), lymphoma (1), Zollinger Ellison syndrome (1), metastatic disease (1), Crohn's disease (1), and wall thickening and duodenitis (5). Normal measurements of the duodenum are described. Abnormalities of wall thickness and duodenal masses required combined HASTE and gadolinium-enhanced SGE images to evaluate well. Abnormalities of the bowel lumen (e.g., diverticula and intussusception), and developmental variants (e.g., malrotation), were sufficiently visualized on HASTE images alone. Bowel inflammation was best shown on gadolinium-enhanced fat suppressed SGE images. HASTE and gadolinium-enhanced fat suppressed SGE sequences are complementary techniques for the demonstration of normal and abnormal duodenum. The combined use of both sequences allows evaluation of different aspects of bowel diseases; abnormalities of position, lumen, and contents are well shown on HASTE

Applying Amide Proton Transfer MR Imaging to Hybrid Brain PET/MR: Concordance with Gadolinium Enhancement and Added Value to [18F]FDG PET.

PubMed

Sun, Hongzan; Xin, Jun; Zhou, Jinyuan; Lu, Zaiming; Guo, Qiyong

2018-06-01

The purpose of this study is to evaluate the diagnostic concordance and metric correlations of amide proton transfer (APT) imaging with gadolinium-enhanced magnetic resonance imaging (MRI) and 2-deoxy-2-[ 18 F-]fluoro-D-glucose ([ 18 F]FDG) positron emission tomography (PET), using hybrid brain PET/MRI. Twenty-one subjects underwent brain gadolinium-enhanced [ 18 F]FDG PET/MRI prospectively. Imaging accuracy was compared between unenhanced MRI, MRI with enhancement, APT-weighted (APTW) images, and PET based on six diagnostic criteria. Among tumors, the McNemar test was further used for concordance assessment between gadolinium-enhanced imaging, APT imaging, and [ 18 F]FDG PET. As well, the relation of metrics between APT imaging and PET was analyzed by the Pearson correlation analysis. APT imaging and gadolinium-enhanced MRI showed superior and similar diagnostic accuracy. APTW signal intensity and gadolinium enhancement were concordant in 19 tumors (100 %), while high [ 18 F]FDG avidity was shown in only 12 (63.2 %). For the metrics from APT imaging and PET, there was significant correlation for 13 hypermetabolic tumors (P < 0.05) and no correlation for the remaining six [ 18 F]FDG-avid tumors. APT imaging can be used to increase diagnostic accuracy with no need to administer gadolinium chelates. APT imaging may provide an added value to [ 18 F]FDG PET in the evaluation of tumor metabolic activity during brain PET/MR studies.

Oligosynaptic inhibition of group Ia afferents from brachioradialis to triceps brachii motor neurons in humans.

PubMed

Sato, Toshiaki; Nito, Mitsuhiro; Suzuki, Katsuhiko; Fujii, Hiromi; Hashizume, Wataru; Miyasaka, Takuji; Shindo, Masaomi; Naito, Akira

2018-01-01

This study examines effects of low-threshold afferents from the brachioradialis (BR) on excitability of triceps brachii (TB) motor neurons in humans. We evaluated the effects using a post stimulus time histogram (PSTH) and electromyogram averaging (EMG-A) methods in 13 healthy human participants. Electrical conditioning stimulation to the radial nerve branch innervating BR with the intensity below the motor threshold was delivered. In the PSTH study, the stimulation produced a trough (inhibition) in 36/69 TB motor units for all the participants. A cutaneous stimulation never provoked such inhibition. The central latency of the inhibition was 1.5 ± 0.5 ms longer than that of the homonymous facilitation. In the EMG-A study, the stimulation produced inhibition in EMG-A of TB in all participants. The inhibition diminished with a tonic vibration stimulation to BR. These findings suggest that oligosynaptic inhibition mediated by group Ia afferents from BR to TB exists in humans. Muscle Nerve 57: 122-128, 2018. © 2017 Wiley Periodicals, Inc.

Polythermal investigation of viscosity of solution of metal carboxylates in VIK-grade mixed carboxylic acids: Yttrium and gadolinium carboxylates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mezhov, E.A.; Samatov, A.V.; Troyanovskii, L.V.

Kinematic viscosities have been measured for solutions of yttrium and gadolinium carboxylates in grade VIK mixed carboxylic acids (MCA). It has been established that the optimal fluidity of these metal carboxylate solutions for application to articles is reached at 333 K. A regression model has been developed to describe the concentration and temperature dependences of the viscosity of yttrium- and gadolinium-containing MCA solutions. 2 refs., 3 tabs.

The performance of hafnium and gadolinium self powered neutron detectors in the TREAT reactor

NASA Astrophysics Data System (ADS)

Imel, G. R.; Hart, P. R.

1996-05-01

The use of gadolinium and hafnium self powered neutron detectors in a transient reactor is described in this paper. The detectors were calibrated to the fission rate of U-235 using calibrated fission chambers; the calibration factors were tested in two reactors in steady state and found to be consistent. Calibration of the detectors in transient reactor conditions was done by using uranium wires that were analyzed by radiochemistry techniques to determine total fissions during the transient. This was correlated to the time-integrated current of the detectors during the transient. A temperature correction factor was derived to account for self-shielding effects in the hafnium and gadolinium detectors. The dynamic response of the detectors under transient conditions was studied, and found to be excellent.

Hypophosphatemia is Associated with the Serial Administration of Triple-Dose Gadolinium to Patients for Brain MRI.

PubMed

Wolansky, Leo J; Cadavid, Diego; Punia, Vineet; Kim, Soyeon; Cheriyan, Jojy; Haghighi, Mershad; Cook, Stuart D

2015-01-01

The purpose of this study is to report a metabolic abnormality associated with frequent, triple-dose Gadolinium (TdGd) use in MS patients during BECOME trial. Potential clinical adverse events and lab abnormalities were monitored at each monthly MRI visit. Hypophosphatemia was defined as phosphate <2.5 mg/dL. Statistical analysis included McNemar's test for pairwise comparisons across visits and generalized estimating equations (GEE) to fit models over time. Eight hundred seventy seven phosphate values were analyzed from the first 12 months. Compared with 4% of subjects at screening, an average of 15.1% (95% confidence interval (CI): 11.4%-19.7%) of patients had hypophosphatemia at visits from months 1 to 12, during which subjects received serial TdGd. Forty four of seventy five (59%) patients developed hypophosphatemia at least once. We also found a significant increasing trend in hypophosphatemia by visit when treatment groups were evaluated together or separately (p < .001). There was a statistically significant decrease in frequency to 9.8% (95% CI: 4.6-19.8%) by month 24 (p = .005) coinciding with a period of less frequent gadolinium administration. Serial TdGd in MS patients, unrelated to immunomodulatory treatment, was associated with increased frequency of hypophosphatemia that progressed with cumulative triple-dose and markedly decreased in second year, with less frequent triple-dose administration. Copyright © 2015 by the American Society of Neuroimaging.

Breakthrough reactions of iodinated and gadolinium contrast media after oral steroid premedication protocol.

PubMed

Jingu, Akiko; Fukuda, Junya; Taketomi-Takahashi, Ayako; Tsushima, Yoshito

2014-10-06

Adverse reactions to iodinated and gadolinium contrast media are an important clinical issue. Although some guidelines have proposed oral steroid premedication protocols to prevent adverse reactions, some patients may have reactions to contrast media in spite of premedication (breakthrough reaction; BTR).The purpose of this study was to assess the frequency, type and severity of BTR when following an oral steroid premedication protocol. All iodinated and gadolinium contrast-enhanced radiologic examinations between August 2011 and February 2013 for which the premedication protocol was applied in our institution were assessed for BTRs. The protocol was applied to a total of 252 examinations (153 patients, ages 15-87 years; 63 males, 90 females). Of these, 152 were for prior acute adverse reactions to contrast media, 85 were for a history of bronchial asthma, and 15 were for other reasons. There were 198 contrast enhanced CTs and 54 contrast enhanced MRIs. There were nine BTR (4.5%) for iodinated contrast media, and only one BTR (1.9%) for gadolinium contrast media: eight were mild and one was moderate. No patient who had a mild index reaction (IR) had a severe BTR. Incidence of BTRs when following the premedication protocol was low. This study by no means proves the efficacy of premedication, but provides some support for following a premedication protocol to improve safety of contrast-enhanced examinations when prior adverse reactions are mild, or when there is a history of asthma.

Breakthrough reactions of iodinated and gadolinium contrast media after oral steroid premedication protocol

PubMed Central

2014-01-01

Background Adverse reactions to iodinated and gadolinium contrast media are an important clinical issue. Although some guidelines have proposed oral steroid premedication protocols to prevent adverse reactions, some patients may have reactions to contrast media in spite of premedication (breakthrough reaction; BTR). The purpose of this study was to assess the frequency, type and severity of BTR when following an oral steroid premedication protocol. Methods All iodinated and gadolinium contrast-enhanced radiologic examinations between August 2011 and February 2013 for which the premedication protocol was applied in our institution were assessed for BTRs. Results The protocol was applied to a total of 252 examinations (153 patients, ages 15–87 years; 63 males, 90 females). Of these, 152 were for prior acute adverse reactions to contrast media, 85 were for a history of bronchial asthma, and 15 were for other reasons. There were 198 contrast enhanced CTs and 54 contrast enhanced MRIs. There were nine BTR (4.5%) for iodinated contrast media, and only one BTR (1.9%) for gadolinium contrast media: eight were mild and one was moderate. No patient who had a mild index reaction (IR) had a severe BTR. Conclusion Incidence of BTRs when following the premedication protocol was low. This study by no means proves the efficacy of premedication, but provides some support for following a premedication protocol to improve safety of contrast-enhanced examinations when prior adverse reactions are mild, or when there is a history of asthma. PMID:25287952

Effect of Cu2+ substitution on the structural, magnetic and electrical properties of gadolinium orthoferrite

NASA Astrophysics Data System (ADS)

Sai Vandana, C.; Hemalatha Rudramadevi, B.

2018-04-01

The pure and copper (Cu) substituted Gadolinium orthoferrites, GdFeO3, GdCu0.1Fe0.9O3, GdCu0.2Fe0.8O3 and GdCu0.3Fe0.7O3 were synthesized by conventional solid state method. The structural, morphological, dielectric, magnetic and impedance properties of Cu substituted Gadolinium orthoferrites have been investigated. The crystallographic phase as well as the substitution of Cu2+ ions in the lattice of GdFeO3 is confirmed from the x-ray diffraction patterns. The Fourier transform infrared spectra exhibit two prominent fundamental absorption peaks at ∼417 cm‑1 and 545 cm‑1. These bands are related to inherent stretching vibrations of metals at octahedral and tetrahedral sites respectively. The coercivity (Hc) and saturation magnetization (Ms) of the synthesized samples at different temperatures were determined from the hysteresis plots. Higher coercive values, 598 Oe and 600 Oe were achieved in GdCu0.1Fe0.9O3 ferrites compared to 527 Oe and 360 Oe in pure GdFeO3 at room temperature (300 K) and low temperature (20 k) respectively. Dielectric dispersion has been observed for gadolinium ferrite samples with Maxwell–Wagner type interfacial polarization. The decrease of dielectric constant and dielectric loss tangent with an increase in frequency was observed. The conduction due to charge hopping between localized states was confirmed from AC conductivity measurements. The composition dependent cationic distributions estimated from XRD, magnetic and electrical studies are in good agreement with each other. The achieved results indicate that the substitution of Cu in gadolinium orthoferrite strongly influences the crystal structure, magnetic and electrical properties thereby making them suitable as multiple state memory devices, transducers, electronic field controlled ferromagnetic resonance devices and spintronic devices.

Serum Neutrophil Gelatinase-Associated Lipocalin and Urinary Kidney Injury Molecule-1 as Potential Biomarkers of Subclinical Nephrotoxicity After Gadolinium-Based and Iodinated-Based Contrast Media Exposure in Pediatric Patients with Normal Kidney Function

PubMed Central

Spasojević-Dimitrijeva, Brankica; Kotur-Stevuljević, Jelena; Đukić, Milan; Paripović, Dušan; Miloševski-Lomić, Gordana; Spasojević-Kalimanovska, Vesna; Pavićević, Polina; Mitrović, Jadranka; Kostić, Mirjana

2017-01-01

Background New renal biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) show promise in early diagnosis of contrast media induced acute kidney injury (CI-AKI). The purpose of our study was to compare the subclinical nephrotoxicity (a condition without changes in standard renal biomarkers) of gadolinium-based contrast media (Gd-DTPA, gadopentetate dimeglumine) and iodinated-based contrast media (iopromide) in pediatric patients with normal kidney function. Material/Methods The first group (n=58) of patients included in the study were undergoing angiography with iopromide, and the second group (n=65) were undergoing magnetic resonance (MR) angiography/urography with Gd-DTPA administration. The concentrations of NGAL and KIM-1 were measured four times in the urine (pre-contrast, then at four hours, 24 hours, and 48 hours after contrast administration), and serum NGAL was measured at 0 (baseline), 24 hours, and 48 hours after contrast exposure. Results After 24 hours, serum NGAL increase of ≥25% was noticed in 32.6% of the patients in the iopromide group and in 25.45% of the patients in the gadolinium group, with significantly higher average percent of this increase in first group (62.23% vs. 36.44%, p=0.002). In the Gd-DTPA group, we observed a statistically significant increase in urinary KIM-1 24 hours after the procedure. Normalized urinary KIM-1, 24 hours after contrast exposure, was a better predictive factor for CI-AKI than other biomarkers (AUC 0.757, cut off 214 pg/mg, sensitivity 83.3%, specificity 54.2%, p=0.035). Conclusions In children with normal renal function, exposure to iodinated-based and gadolinium-based media might lead to subclinical nephrotoxicity, which could be detected using serum NGAL and urinary KIM-1. PMID:28874655

Involvement of functional groups on the surface of carboxyl group-terminated polyamidoamine dendrimers bearing arbutin in inhibition of Na⁺/glucose cotransporter 1 (SGLT1)-mediated D-glucose uptake.

PubMed

Sakuma, Shinji; Kanamitsu, Shun; Teraoka, Yumi; Masaoka, Yoshie; Kataoka, Makoto; Yamashita, Shinji; Shirasaka, Yoshiyuki; Tamai, Ikumi; Muraoka, Masahiro; Nakatsuji, Yohji; Kida, Toshiyuki; Akashi, Mitsuru

2012-04-02

A carboxyl group-terminated polyamidoamine dendrimer (generation: 3.0) bearing arbutin, which is a substrate of Na⁺/glucose cotransporter 1 (SGLT1), via a nonbiodegradable ω-amino triethylene glycol linker (PAMAM-ARB), inhibits SGLT1-mediated D-glucose uptake, as does phloridzin, which is a typical SGLT1 inhibitor. Here, since our previous research revealed that the activity of arbutin was dramatically improved through conjugation with the dendrimer, we examined the involvement of functional groups on the dendrimer surface in inhibition of SGLT1-mediated D-glucose uptake. PAMAM-ARB, with a 6.25% arbutin content, inhibited in vitro D-glucose uptake most strongly; the inhibitory effect decreased as the arbutin content increased. In vitro experiments using arbutin-free original dendrimers indicated that dendrimer-derived carboxyl groups actively participated in SGLT1 inhibition. However, the inhibitory effect was much less than that of PAMAM-ARB and was equal to that of glucose moiety-free PAMAM-ARB. Data supported that the glucose moiety of arbutin was essential for the high activity of PAMAM-ARB in SGLT1 inhibition. Analysis of the balance of each domain further suggested that carboxyl groups anchored PAMAM-ARB to SGLT1, and the subsequent binding of arbutin-derived glucose moieties to the target sites on SGLT1 resulted in strong inhibition of SGLT1-mediated D-glucose uptake.

Apparent diffusion coefficient for molecular subtyping of non-gadolinium-enhancing WHO grade II/III glioma: volumetric segmentation versus two-dimensional region of interest analysis.

PubMed

Thust, S C; Hassanein, S; Bisdas, S; Rees, J H; Hyare, H; Maynard, J A; Brandner, S; Tur, C; Jäger, H R; Yousry, T A; Mancini, L

2018-03-23

To investigate if quantitative apparent diffusion coefficient (ADC) measurements can predict genetic subtypes of non-gadolinium-enhancing gliomas, comparing whole tumour against single slice analysis. Volumetric T2-derived masks of 44 gliomas were co-registered to ADC maps with ADC mean (ADC mean ) calculated. For the slice analysis, two observers placed regions of interest in the largest tumour cross-section. The ratio (ADC ratio ) between ADC mean in the tumour and normal appearing white matter was calculated for both methods. Isocitrate dehydrogenase (IDH) wild-type gliomas showed the lowest ADC values throughout (p < 0.001). ADC mean in the IDH-mutant 1p19q intact group was significantly higher than in the IDH-mutant 1p19q co-deleted group (p < 0.01). A volumetric ADC mean threshold of 1201 × 10 -6 mm 2 /s identified IDH wild-type with a sensitivity of 83% and a specificity of 86%; a volumetric ADC ratio cut-off value of 1.65 provided a sensitivity of 80% and a specificity of 92% (area under the curve (AUC) 0.9-0.94). A slice ADC ratio threshold for observer 1 (observer 2) of 1.76 (1.83) provided a sensitivity of 80% (86%), specificity of 91% (100%) and AUC of 0.95 (0.96). The intraclass correlation coefficient was excellent (0.98). ADC measurements can support the distinction of glioma subtypes. Volumetric and two-dimensional measurements yielded similar results in this study. • Diffusion-weighted MRI aids the identification of non-gadolinium-enhancing malignant gliomas • ADC measurements may permit non-gadolinium-enhancing glioma molecular subtyping • IDH wild-type gliomas have lower ADC values than IDH-mutant tumours • Single cross-section and volumetric ADC measurements yielded comparable results in this study.

Application of an oscillation-type linear cadmium telluride detector to enhanced gadolinium K-edge computed tomography

NASA Astrophysics Data System (ADS)

Matsukiyo, Hiroshi; Sato, Eiichi; Hagiwara, Osahiko; Abudurexiti, Abulajiang; Osawa, Akihiro; Enomoto, Toshiyuki; Watanabe, Manabu; Nagao, Jiro; Sato, Shigehiro; Ogawa, Akira; Onagawa, Jun

2011-03-01

A linear cadmium telluride (CdTe) detector is useful for carrying out energy-discrimination X-ray imaging, including computed tomography (CT). To perform enhanced gadolinium K-edge CT, we used an oscillation-type linear CdTe detector with an energy resolution of 1.2 keV. CT is performed by repeating the linear scan and the rotation of an object. Penetrating X-ray photons from the object are detected by the CdTe detector, and event signals of X-ray photons are produced using charge-sensitive and shaping amplifiers. Both the photon energy and the energy width are selected using a multichannel analyzer, and the number of photons is counted by a counter card. In energy-discrimination CT, tube voltage and current were 80 kV and 20 μA, respectively, and X-ray intensity was 1.55 μGy/s at 1.0 m from the source at a tube voltage of 80 kV. Demonstration of enhanced gadolinium K-edge X-ray CT was carried out by selecting photons with energies just beyond gadolinium K-edge energy of 50.3 keV.

Role of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging in the management of hepatocellular carcinoma: consensus at the Symposium of the 48th Annual Meeting of the Liver Cancer Study Group of Japan.

PubMed

Kudo, Masatoshi; Matsui, Osamu; Sakamoto, Michiie; Kitao, Azusa; Kim, Tonsok; Ariizumi, Shun-ichi; Ichikawa, Tomoaki; Kobayashi, Satoshi; Imai, Yasuharu; Izumi, Namiki; Fujinaga, Yasunari; Arii, Shigeki

2013-01-01

We summarize here the consensus reached at the Symposium of the 48th Annual Meeting of the Liver Cancer Study Group of Japan held in Kanazawa on July 20th and 21st, 2012, on the role of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) in the management of hepatocellular carcinoma (HCC). Currently, dynamic CT is the first choice of imaging modality when HCC is suspected. EOB-MRI is useful for differentiation and definitive diagnosis of HCC when dynamic CT/MRI does not show conclusive findings for HCC. In addition, contrast- enhanced ultrasound with Sonazoid is useful for making a decision on whether or not to treat a hypovascular lesion <1 cm when the nodules are shown with low intensity in the hepatocyte phase of EOB-MRI. Furthermore, EOB-MRI should be performed in selected cases of HCC ultrahigh-risk groups every 3-4 months, or EOB-MRI should be performed at least once at the first visit in all HCC ultrahigh-risk groups. Copyright © 2013 S. Karger AG, Basel.

3-Hydroxypyridin-2-thione as Novel Zinc Binding Group for Selective Histone Deacetylase Inhibition

PubMed Central

Patil, Vishal; Sodji, Quaovi H.; Kornacki, James R.; Mrksich, Milan; Oyelere, Adegboyega K.

2013-01-01

Small molecules bearing hydroxamic acid as the zinc binding group (ZBG) have been the most effective histone deacetylase inhibitor (HDACi) to date. However, concerns about the pharmacokinetic liabilities of the hydroxamic acid moiety have stimulated research efforts aimed at finding alternative non-hydroxamate ZBGs. We have identified 3-hydroxypyridin-2-thione (3-HPT) as a novel ZBG that is compatible with HDAC inhibition. 3-HPT inhibits HDAC 6 and HDAC 8 with an IC50 of 681 nM and 3675 nM respectively. Remarkably, 3-HPT gives no inhibition of HDAC 1. Subsequent optimization led to several novel 3HPT-based HDACi that are selective for HDAC 6 and HDAC 8. Furthermore, a subset of these inhibitors induces apoptosis in various cancer cell lines. PMID:23547652

3-Hydroxypyridin-2-thione as novel zinc binding group for selective histone deacetylase inhibition.

PubMed

Patil, Vishal; Sodji, Quaovi H; Kornacki, James R; Mrksich, Milan; Oyelere, Adegboyega K

2013-05-09

Small molecules bearing hydroxamic acid as the zinc binding group (ZBG) have been the most effective histone deacetylase inhibitors (HDACi) to date. However, concerns about the pharmacokinetic liabilities of the hydroxamic acid moiety have stimulated research efforts aimed at finding alternative nonhydroxamate ZBGs. We have identified 3-hydroxypyridin-2-thione (3-HPT) as a novel ZBG that is compatible with HDAC inhibition. 3-HPT inhibits HDAC 6 and HDAC 8 with an IC50 of 681 and 3675 nM, respectively. Remarkably, 3-HPT gives no inhibition of HDAC 1. Subsequent optimization led to several novel 3HPT-based HDACi that are selective for HDAC 6 and HDAC 8. Furthermore, a subset of these inhibitors induces apoptosis in various cancer cell lines.

Deep learning enables reduced gadolinium dose for contrast-enhanced brain MRI.

PubMed

Gong, Enhao; Pauly, John M; Wintermark, Max; Zaharchuk, Greg

2018-02-13

There are concerns over gadolinium deposition from gadolinium-based contrast agents (GBCA) administration. To reduce gadolinium dose in contrast-enhanced brain MRI using a deep learning method. Retrospective, crossover. Sixty patients receiving clinically indicated contrast-enhanced brain MRI. 3D T 1 -weighted inversion-recovery prepped fast-spoiled-gradient-echo (IR-FSPGR) imaging was acquired at both 1.5T and 3T. In 60 brain MRI exams, the IR-FSPGR sequence was obtained under three conditions: precontrast, postcontrast images with 10% low-dose (0.01mmol/kg) and 100% full-dose (0.1 mmol/kg) of gadobenate dimeglumine. We trained a deep learning model using the first 10 cases (with mixed indications) to approximate full-dose images from the precontrast and low-dose images. Synthesized full-dose images were created using the trained model in two test sets: 20 patients with mixed indications and 30 patients with glioma. For both test sets, low-dose, true full-dose, and the synthesized full-dose postcontrast image sets were compared quantitatively using peak-signal-to-noise-ratios (PSNR) and structural-similarity-index (SSIM). For the test set comprised of 20 patients with mixed indications, two neuroradiologists scored blindly and independently for the three postcontrast image sets, evaluating image quality, motion-artifact suppression, and contrast enhancement compared with precontrast images. Results were assessed using paired t-tests and noninferiority tests. The proposed deep learning method yielded significant (n = 50, P < 0.001) improvements over the low-dose images (>5 dB PSNR gains and >11.0% SSIM). Ratings on image quality (n = 20, P = 0.003) and contrast enhancement (n = 20, P < 0.001) were significantly increased. Compared to true full-dose images, the synthesized full-dose images have a slight but not significant reduction in image quality (n = 20, P = 0.083) and contrast enhancement (n = 20, P = 0.068). Slightly

Imaging of cauda equina edema in lumbar canal stenosis by using gadolinium-enhanced MR imaging: experimental constriction injury.

PubMed

Kobayashi, S; Uchida, K; Takeno, K; Baba, H; Suzuki, Y; Hayakawa, K; Yoshizawa, H

2006-02-01

It has been reported that disturbance of blood flow arising from circumferential compression of the cauda equina by surrounding tissue plays a major role in the appearance of neurogenic intermittent claudication (NIC) associated with lumbar spinal canal stenosis (LSCS). We created a model of LSCS to clarify the mechanism of enhancement within the cauda equina on gadolinium-enhanced MR images from patients with LSCS. In 20 dogs, a lumbar laminectomy was performed by applying circumferential constriction to the cauda equina by using a silicon tube, to produce 30% stenosis of the circumferential diameter of the dural tube. After 1 and 3 weeks, gadolinium and Evans blue albumin were injected intravenously at the same time. The sections were used to investigate the status of the blood-nerve barrier function under a fluorescence microscope and we compared gadolinium-enhanced MR images with Evans blue albumin distribution in the nerve. The other sections were used for light and transmission electron microscopic study. In this model, histologic examination showed congestion and dilation in many of the intraradicular veins, as well as inflammatory cell infiltration. The intraradicular edema caused by venous congestion and Wallerian degeneration can also occur at sites that are not subject to mechanical compression. Enhanced MR imaging showed enhancement of the cauda equina at the stenosed region, demonstrating the presence of edema. Gadolinium-enhanced MR imaging may be a useful tool for the diagnosis of microcirculatory disorders of the cauda equina associated with LSCS.

In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging.

PubMed

Gu, Meng-Jie; Li, Kun-Feng; Zhang, Lan-Xin; Wang, Huan; Liu, Li-Si; Zheng, Zhuo-Zhao; Han, Nan-Yin; Yang, Zhen-Jun; Fan, Tian-Yuan

2015-01-01

Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N'-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor.

In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging

PubMed Central

Gu, Meng-Jie; Li, Kun-Feng; Zhang, Lan-Xin; Wang, Huan; Liu, Li-Si; Zheng, Zhuo-Zhao; Han, Nan-Yin; Yang, Zhen-Jun; Fan, Tian-Yuan

2015-01-01

Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N′-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor. PMID:26316749

High-pressure high-temperature phase diagram of gadolinium studied using a boron-doped heater anvil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montgomery, J. M.; Samudrala, G. K.; Vohra, Y. K.

A boron-doped designer heater anvil is used in conjunction with powder x-ray diffraction to collect structural information on a sample of quasi-hydrostatically loaded gadolinium metal up to pressures above 8 GPa and 600 K. The heater anvil consists of a natural diamond anvil that has been surface modified with a homoepitaxially grown chemical-vapor-deposited layer of conducting boron-doped diamond, and is used as a DC heating element. Internally insulating both diamond anvils with sapphire support seats allows for heating and cooling of the high-pressure area on the order of a few tens of seconds. This device is then used to scan the phasemore » diagram of the sample by oscillating the temperature while continuously increasing the externally applied pressure and collecting in situ time-resolved powder diffraction images. In the pressure-temperature range covered in this experiment, the gadolinium sample is observed in its hcp, αSm, and dhcp phases. Under this temperature cycling, the hcp → αSm transition proceeds in discontinuous steps at points along the expected phase boundary. From these measurements (representing only one hour of synchrotron x-ray collection time), a single-experiment equation of state and phase diagram of each phase of gadolinium is presented for the range of 0–10 GPa and 300–650 K.« less

High-pressure high-temperature phase diagram of gadolinium studied using a boron-doped heater anvil

NASA Astrophysics Data System (ADS)

Montgomery, J. M.; Samudrala, G. K.; Velisavljevic, N.; Vohra, Y. K.

2016-04-01

A boron-doped designer heater anvil is used in conjunction with powder x-ray diffraction to collect structural information on a sample of quasi-hydrostatically loaded gadolinium metal up to pressures above 8 GPa and 600 K. The heater anvil consists of a natural diamond anvil that has been surface modified with a homoepitaxially grown chemical-vapor-deposited layer of conducting boron-doped diamond, and is used as a DC heating element. Internally insulating both diamond anvils with sapphire support seats allows for heating and cooling of the high-pressure area on the order of a few tens of seconds. This device is then used to scan the phase diagram of the sample by oscillating the temperature while continuously increasing the externally applied pressure and collecting in situ time-resolved powder diffraction images. In the pressure-temperature range covered in this experiment, the gadolinium sample is observed in its hcp, αSm, and dhcp phases. Under this temperature cycling, the hcp → αSm transition proceeds in discontinuous steps at points along the expected phase boundary. From these measurements (representing only one hour of synchrotron x-ray collection time), a single-experiment equation of state and phase diagram of each phase of gadolinium is presented for the range of 0-10 GPa and 300-650 K.

Disparate ultrafast dynamics of itinerant and localized magnetic moments in gadolinium metal

PubMed Central

Frietsch, B.; Bowlan, J.; Carley, R.; Teichmann, M.; Wienholdt, S.; Hinzke, D.; Nowak, U.; Carva, K.; Oppeneer, P. M.; Weinelt, M.

2015-01-01

The Heisenberg–Dirac intra-atomic exchange coupling is responsible for the formation of the atomic spin moment and thus the strongest interaction in magnetism. Therefore, it is generally assumed that intra-atomic exchange leads to a quasi-instantaneous aligning process in the magnetic moment dynamics of spins in separate, on-site atomic orbitals. Following ultrashort optical excitation of gadolinium metal, we concurrently record in photoemission the 4f magnetic linear dichroism and 5d exchange splitting. Their dynamics differ by one order of magnitude, with decay constants of 14 versus 0.8 ps, respectively. Spin dynamics simulations based on an orbital-resolved Heisenberg Hamiltonian combined with first-principles calculations explain the particular dynamics of 5d and 4f spin moments well, and corroborate that the 5d exchange splitting traces closely the 5d spin-moment dynamics. Thus gadolinium shows disparate dynamics of the localized 4f and the itinerant 5d spin moments, demonstrating a breakdown of their intra-atomic exchange alignment on a picosecond timescale. PMID:26355196

Group I mGlu receptor stimulation inhibits activation-induced cell death of human T lymphocytes

PubMed Central

Chiocchetti, Annalisa; Miglio, Gianluca; Mesturini, Riccardo; Varsaldi, Federica; Mocellin, Marco; Orilieri, Elisabetta; Dianzani, Chiara; Fantozzi, Roberto; Dianzani, Umberto; Lombardi, Grazia

2006-01-01

The effects of L-glutamate on activation-induced cell death (AICD) of human activated (1 μg ml−1 phytohemagglutinin plus 2 U ml−1 interleukin-2; 8 days) T lymphocytes were studied by measuring anti-CD3 monoclonal antibody (10 μg ml−1; 18 h)-induced cell apoptosis (Annexin V and propidium iodide staining). L-Glutamate (1 × 10−8–1 × 10−4 M) significantly (P⩽0.01) inhibited AICD in a concentration-dependent manner (EC50=6.3 × 10−8 M; maximum inhibition 54.8±6.3% at 1 × 10−6 M). The L-glutamate inhibitory effect was pharmacologically characterized as mediated by group I mGlu receptors, since mGlu receptor agonists reproduced this effect. The EC50 values were: 3.2 × 10−7 M for (1S,3R)-ACPD; 4.5 × 10−8 M for quisqualate; 1.0 × 10−6 M for (S)-3,5-DHPG; 2.0 × 10−5 M for CHPG. Group I mGlu receptor antagonists inhibited the effects of quisqualate 1.0 × 10−6 M. The IC50 values calculated were: 8.7 × 10−5, 4.3 × 10−6 and 6.3 × 10−7 M for AIDA, LY 367385 and MPEP, respectively. L-Glutamate (1 × 10−6 M; 18 h) significantly (P⩽0.05) inhibited FasL expression (40.8±11.3%) (cytofluorimetric analysis), whereas it did not affect Fas signalling. Expression of both mGlu1 and mGlu5 receptor mRNA by T lymphocytes and T-cell lines, as demonstrated by reverse transcriptase–PCR analysis, suggests that L-glutamate-mediated inhibition of AICD was exerted on T cells. These data depict a novel role for L-glutamate in the regulation of the immune response through group I mGlu receptor-mediated mechanisms. PMID:16751798

Transient arterial phase respiratory motion-related artifact in MR imaging of the liver: an analysis of four different gadolinium-based contrast agents.

PubMed

Shah, Mansi R; Flusberg, Milana; Paroder, Viktoriya; Rozenblit, Alla M; Chernyak, Victoria

The purpose was to compare hepatic arterial phase (HAP) respiratory motion artifact (RMA) between gadoxetate, gadobutrol, gadopentetate, and gadobenate. Two hundred cases of each gadolinium agent were included. RMA was assigned using 5-point Likert scale (1=no motion, 5=extreme motion) on precontrast and HAP. RMA increase (increase ≥1 on HAP from precontrast) was the outcome in logistic regression. Odds of RMA increase for gadoxetate were 5.5 (P<.001), 3.6 (P=.034), and 9.5 (P<.001) times higher than gadobutrol, gadopentetate, and gadobenate, respectively. Gadolinium volume and dose were not independent predictors of RMA increase. Gadoxetate has increased odds of RMA compared with other gadolinium agents; tight contrast bolus is not a contributor. Copyright © 2016 Elsevier Inc. All rights reserved.

Gadolinium released by the linear gadolinium-based contrast-agent Gd-DTPA decreases the activity of human epithelial Na+ channels (ENaCs).

PubMed

Knoepp, Fenja; Bettmer, Joerg; Fronius, Martin

2017-05-01

Gadolinium-based-contrast-agents (GBCAs) are used for magnetic-resonance-imaging and associated with renal and cardiovascular adverse reactions caused by released Gd 3+ ions. Gd 3+ is also a modulator of mechano-gated ion channels, including the epithelial Na + channel (ENaC) that is expressed in kidney epithelium and the vasculature. ENaC is important for salt-/water homeostasis and blood pressure regulation and a likely target of released Gd 3+ from GBCAs causing the above-mentioned adverse reactions. Therefore this study examined the effect of Gd 3+ and GBCAs on ENaC's activity. Human αβγENaC was expressed in Xenopus laevis oocytes and exposed to Gd 3+ , linear (Gd-DTPA, Magnevist) or cyclic (Dotarem) GBCAs. Transmembrane ion-currents (I M ) were recorded by the two-electrode-voltage-clamp technique and Gd 3+ -release by Gd-DTPA was confirmed by inductively coupled plasma-mass spectrometry. Gd 3+ exerts biphasic effects on ENaC's activity: ≤0.3mmol/l decreased I M which was preventable by DEPC (modifies histidines). Strikingly Gd 3+ ≥0.4mmol/l increased I M and this effect was prevented by cysteine-modifying MTSEA. Linear Gd-DTPA and Magnevist mimicked the effect of ≤0.3mmol/l Gd 3+ , whereas the chelator DTPA showed no effect. Gd 3+ and Gd-DTPA increased the IC 50 for amiloride, but did not affect ENaC's self-inhibition. Interestingly, cyclic Gd-DOTA (Dotarem) increased I M to a similar extent as its chelator DOTA, suggesting that the chelator rather than released Gd 3+ is responsible for this effect. These results confirm Gd 3+ -release from linear Gd-DTPA and indicate that the released Gd 3+ amount is sufficient to interfere with ENaC's activity to provide putative explanations for GBCA-related adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Gadolinium-enhanced inner ear magnetic resonance imaging for evaluation of delayed endolymphatic hydrops, including a bilateral case.

PubMed

Fukushima, Munehisa; Oya, Ryohei; Akazawa, Hitoshi; Tsuruta, Yukinori; Inohara, Hidenori

2016-01-01

The data suggests that gadolinium-enhanced inner ear MR imaging is useful for diagnosis of delayed endolymphatic hydrops (DEH) because it is independent of inner ear function, and the size of the affected endolymphatic space is clearly enlarged. This study was performed to semi-quantitatively evaluate the endolymphatic space in patients with all types of DEH using gadolinium-enhanced inner ear magnetic resonance (MR) imaging. Seven patients (age range = 21-77 years; five female, two male) with ipsilateral DEH (n = 5), contralateral DEH (n = 1), and bilateral DEH (n = 1). All patients underwent 3T MR imaging 4 h after intravenous injection of gadolinium. Software was used to determine the size of the endolymphatic space. Pure tone audiometry and caloric testing using an electronystagmogram were carried out. One side of the endolymphatic space was dominantly extended in patients with ipsilateral DEH, and both sides of the space were extended in patients with contralateral and bilateral DEH. In patients with ipsilateral DEH, the volume ratio of endolymph to vestibule was 2.5-4.3-times that in the unaffected ear. The volume ratio of endolymph to vestibule was nearly equal in patients with contralateral and bilateral DEH.

Monte Carlo simulation of energy absorbed in phenolic ESR dosimeters added with gadolinium exposed to thermal, epithermal and fast neutrons

NASA Astrophysics Data System (ADS)

Longo, A.; Collura, G.; Gallo, S.; Bartolotta, A.; Marrale, M.

2017-11-01

In this work analyses of the energy released per unit mass in phenolic compound exposed to neutron beams were performed with the aim of predicting the increase in dose achievable by addition of gadolinium (Gd) inside the pellets. In particular, Monte Carlo (MC) simulations were carried out for IRGANOX® 1076 phenolic compound irradiated with neutron beams with different energy spectra at various depths inside a water phantom. The addition of gadolinium increases sensitivity of phenolic ESR (electron spin resonance) dosimeters to neutrons thanks to the high gadolinium cross section for neutron capture and to the large number of secondary particles (mainly Auger and internal conversion electrons) which are able to release energy inside the sensitive material layers. For small depths in water phantom and low energy neutron spectra the increase in dose due to gadolinium is large (more than a factor 50). The enhancement is smaller in case of epithermal neutron beam, whereas the increase in dose for fast neutrons is less than 50%. In order to have a comparison with other ESR dosimeters the energy released per unit mass in phenolic compound was compared with that calculated in alanine pellets. For thermal neutron beams the energy released in phenolic compound with gadolinium is comparable to that released in alanine for small depths in phantom, whereas it is larger than in alanine for large depths. In case of epithermal and fast neutron beams the energy released in phenolic compound is larger than in alanine samples because the elastic scattering with hydrogen nuclei is more probable for high neutron energies and this phenolic compound is characterized by an higher number of 1H nuclei than alanine. All results here found suggest that these phenolic pellets could be fruitfully used for dosimetric applications in Neutron Capture Therapy.

Gadolinium chelate coated gold nanoparticles as contrast agents for both X-ray computed tomography and magnetic resonance imaging.

PubMed

Alric, Christophe; Taleb, Jacqueline; Le Duc, Géraldine; Mandon, Céline; Billotey, Claire; Le Meur-Herland, Alice; Brochard, Thierry; Vocanson, Francis; Janier, Marc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier

2008-05-07

Functionalized gold nanoparticles were applied as contrast agents for both in vivo X-ray and magnetic resonance imaging. These particles were obtained by encapsulating gold cores within a multilayered organic shell which is composed of gadolinium chelates bound to each other through disulfide bonds. The contrast enhancement in MRI stems from the presence of gadolinium ions which are entrapped in the organic shell, whereas the gold core provides a strong X-ray absorption. This study revealed that these particles suited for dual modality imaging freely circulate in the blood vessels without undesirable accumulation in the lungs, spleen, and liver.

Bioconjugation of luminescent silicon quantum dots to gadolinium ions for bioimaging applications

NASA Astrophysics Data System (ADS)

Erogbogbo, Folarin; Chang, Ching-Wen; May, Jasmine L.; Liu, Liwei; Kumar, Rajiv; Law, Wing-Cheung; Ding, Hong; Yong, Ken Tye; Roy, Indrajit; Sheshadri, Mukund; Swihart, Mark T.; Prasad, Paras N.

2012-08-01

Luminescent imaging agents and MRI contrast agents are desirable components in the rational design of multifunctional nanoconstructs for biological imaging applications. Luminescent biocompatible silicon quantum dots (SiQDs) and gadolinium chelates can be applied for fluorescence microscopy and MRI, respectively. Here, we report the first synthesis of a nanocomplex incorporating SiQDs and gadolinium ions (Gd3+) for biological applications. The nanoconstruct is composed of a PEGylated micelle, with hydrophobic SiQDs in its core, covalently bound to DOTA-chelated Gd3+. Dynamic light scattering reveals a radius of 85 nm for these nanoconstructs, which is consistent with the electron microscopy results depicting radii ranging from 25 to 60 nm. Cellular uptake of the probes verified that they maintain their optical properties within the intracellular environment. The magnetic resonance relaxivity of the nanoconstruct was 2.4 mM-1 s-1 (in terms of Gd3+ concentration), calculated to be around 6000 mM-1 s-1 per nanoconstruct. These desirable optical and relaxivity properties of the newly developed probe open the door for use of SiQDs in future multimodal applications such as tumour imaging.Luminescent imaging agents and MRI contrast agents are desirable components in the rational design of multifunctional nanoconstructs for biological imaging applications. Luminescent biocompatible silicon quantum dots (SiQDs) and gadolinium chelates can be applied for fluorescence microscopy and MRI, respectively. Here, we report the first synthesis of a nanocomplex incorporating SiQDs and gadolinium ions (Gd3+) for biological applications. The nanoconstruct is composed of a PEGylated micelle, with hydrophobic SiQDs in its core, covalently bound to DOTA-chelated Gd3+. Dynamic light scattering reveals a radius of 85 nm for these nanoconstructs, which is consistent with the electron microscopy results depicting radii ranging from 25 to 60 nm. Cellular uptake of the probes verified that they

Tissue gadolinium deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA: evaluation with inductively coupled plasma mass spectrometry (ICP-MS).

PubMed

Sato, Tomohiro; Tamada, Tsutomu; Watanabe, Shigeru; Nishimura, Hirotake; Kanki, Akihiko; Noda, Yasufumi; Higaki, Atsushi; Yamamoto, Akira; Ito, Katsuyoshi

2015-06-01

This study was undertaken to quantify tissue gadolinium (Gd) deposition in hepatorenally impaired rats exposed to gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) by means of inductively coupled plasma mass spectrometry (ICP-MS) and to compare differences in Gd distribution among major organs as possible triggers for nephrogenic systemic fibrosis. Five hepatorenally impaired rats (5/6-nephrectomized, with carbon-tetrachloride-induced liver fibrosis) were injected with Gd-EOB-DTPA. Histological assessment was conducted and Gd content of the skin, liver, kidneys, lungs, heart, spleen, diaphragm, and femoral muscle was measured by inductively coupled plasma mass spectrometry (ICP-MS) at 7 days after last injection. In addition, five renally impaired rats were injected with Gd-EOB-DTPA and the degree of tissue Gd deposition was compared with that in the hepatorenally impaired rats. ICP-MS analysis revealed significantly higher Gd deposition in the kidneys, spleen, and liver (p = 0.009-0.047) in the hepatorenally impaired group (42.6 ± 20.1, 17.2 ± 6.1, 8.4 ± 3.2 μg/g, respectively) than in the renally impaired group (17.2 ± 7.7, 5.4 ± 2.1, 2.8 ± 0.7 μg/g, respectively); no significant difference was found for other organs. In the hepatorenally impaired group, Gd was predominantly deposited in the kidneys, followed by the spleen, liver, lungs, skin, heart, diaphragm, and femoral muscle. Histopathological investigation revealed hepatic fibrosis in the hepatorenally impaired group. Compared with renally impaired rats, tissue Gd deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA was significantly increased in the kidneys, spleen, and liver, probably due to the impairment of the dual excretion pathways of the urinary and biliary systems.

Removal of gadolinium nitrate from heavy water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilde, E.W.

2000-03-22

Work was conducted to develop a cost-effective process to purify 181 55-gallon drums containing spent heavy water moderator (D2O) contaminated with high concentrations of gadolinium nitrate, a chemical used as a neutron poison during former nuclear reactor operations at the Savannah River Site (SRS). These drums also contain low level radioactive contamination, including tritium, which complicates treatment options. Presently, the drums of degraded moderator are being stored on site. It was suggested that a process utilizing biological mechanisms could potentially lower the total cost of heavy water purification by allowing the use of smaller equipment with less product loss andmore » a reduction in the quantity of secondary waste materials produced by the current baseline process (ion exchange).« less

Studies of MRI relaxivities of gadolinium-labeled dendrons

NASA Astrophysics Data System (ADS)

Pan, Hongmu; Daniel, Marie-Christine

2011-05-01

In cancer detection, imaging techniques have a great importance in early diagnosis. The more sensitive the imaging technique and the earlier the tumor can be detected. Contrast agents have the capability to increase the sensitivity in imaging techniques such as magnetic resonance imaging (MRI). Until now, gadolinium-based contrast agents are mainly used for MRI, and show good enhancement. But improvement is needed for detection of smaller tumors at the earliest stage possible. The dendrons complexed with Gd(DOTA) were synthesized and evaluated as a new MRI contrast agent. The longitudinal and transverse relaxation effects were tested and compared with commercial drug Magnevist, Gd(DTPA).

Insights into the use of gadolinium and gadolinium/boron-based agents in imaging-guided neutron capture therapy applications.

PubMed

Deagostino, Annamaria; Protti, Nicoletta; Alberti, Diego; Boggio, Paolo; Bortolussi, Silva; Altieri, Saverio; Crich, Simonetta Geninatti

2016-05-01

Gadolinium neutron capture therapy (Gd-NCT) is currently under development as an alternative approach for cancer therapy. All of the clinical experience to date with NCT is done with (10)B, known as boron neutron capture therapy (BNCT), a binary treatment combining neutron irradiation with the delivery of boron-containing compounds to tumors. Currently, the use of Gd for NCT has been getting more attention because of its highest neutron cross-section. Although Gd-NCT was first proposed many years ago, its development has suffered due to lack of appropriate tumor-selective Gd agents. This review aims to highlight the recent advances for the design, synthesis and biological testing of new Gd- and B-Gd-containing compounds with the task of finding the best systems able to improve the NCT clinical outcome.

High-pressure high-temperature phase diagram of gadolinium studied using a boron-doped heater anvil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montgomery, J. M.; Samudrala, G. K.; Velisavljevic, N.

A boron-doped designer heater anvil is used in conjunction with powder x-ray diffraction to collect structural information on a sample of quasi-hydrostatically loaded gadolinium metal up to pressures above 8 GPa and 600 K. The heater anvil consists of a natural diamond anvil that has been surface modified with a homoepitaxially-grown chemical-vapor-deposited layer of conducting boron-doped diamond, and is used as a DC heating element. Internally insulating both diamond anvils with sapphire support seats allows for heating and cooling of the high pressure area on the order of a few tens of seconds. This device is then used to scanmore » the phase diagram of the sample by oscillating the temperature while continuously increasing the externally applied pressure and collecting in situ time-resolved powder diffraction images. In the pressure-temperature range covered in the experiment the gadolinium sample is observed in its hcp, αSm, and dhcp phases. Under this temperature cycling, the hcp→αSm transition proceeds in discontinuous steps at points along the expected phase boundary. Additionally, the unit cell volumes of each phase deviate from the expected thermal expansion behavior just before each transition is observed from the diffraction data. From these measurements (representing only one hour of synchrotron x-ray collection time), a single-experiment equation of state and phase diagram of each phase of gadolinium is presented for the range of 0 - 10 GPa and 300 - 650 K.« less

Quantitative assessment of the rheumatoid synovial microvascular bed by gadolinium-DTPA enhanced magnetic resonance imaging

PubMed Central

Gaffney, K.; Cookson, J.; Blades, S.; Coumbe, A.; Blake, D.

1998-01-01

OBJECTIVE—To examine the relation between rate of synovial membrane enhancement, intra-articular pressure (IAP), and histologically determined synovial vascularity in rheumatoid arthritis, using gadolinium-DTPA enhanced magnetic resonance imaging (MRI).
METHODS—Dynamic gadolinium-DTPA enhanced MRI was performed in 31 patients with knee synovitis (10 patients IAP study, 21 patients vascular morphometry study). Rate of synovial membrane enhancement was quantified by line profile analysis using the image processing package ANALYZE. IAP was measured using an intra-compartmental pressure monitor system. Multiple synovial biopsy specimens were obtained by a blind biopsy technique. Blood vessels were identified immunohistochemically using the endothelial cell marker QBend30 and quantified (blood vessel numerical density and fractional area).
RESULTS—Median blood vessel numerical density and fractional area were 77.5/mm2 (IQR; 69.3-110.7) and 5.6% (IQR; 3.4-8.5) respectively. The rate of synovial membrane enhancement (median 2.74 signal intensity units/s, IQR 2.0-3.8) correlated with both blood vessel numerical density (r = 0.46, p < 0.05) and blood vessel fractional area (r = 0.55, p < 0.02). IAP did not influence the rate of enhancement.
CONCLUSIONS—Gadolinium-DTPA enhanced MRI may prove to be a valuable technique for evaluating drugs that influence angiogenesis.

 Keywords: magnetic resonance imaging; rheumatoid arthritis; synovitis; vascularity PMID:9640130

High-pressure high-temperature phase diagram of gadolinium studied using a boron-doped heater anvil

DOE PAGES

Montgomery, J. M.; Samudrala, G. K.; Velisavljevic, N.; ...

2016-04-07

A boron-doped designer heater anvil is used in conjunction with powder x-ray diffraction to collect structural information on a sample of quasi-hydrostatically loaded gadolinium metal up to pressures above 8 GPa and 600 K. The heater anvil consists of a natural diamond anvil that has been surface modified with a homoepitaxially-grown chemical-vapor-deposited layer of conducting boron-doped diamond, and is used as a DC heating element. Internally insulating both diamond anvils with sapphire support seats allows for heating and cooling of the high pressure area on the order of a few tens of seconds. This device is then used to scanmore » the phase diagram of the sample by oscillating the temperature while continuously increasing the externally applied pressure and collecting in situ time-resolved powder diffraction images. In the pressure-temperature range covered in the experiment the gadolinium sample is observed in its hcp, αSm, and dhcp phases. Under this temperature cycling, the hcp→αSm transition proceeds in discontinuous steps at points along the expected phase boundary. Additionally, the unit cell volumes of each phase deviate from the expected thermal expansion behavior just before each transition is observed from the diffraction data. From these measurements (representing only one hour of synchrotron x-ray collection time), a single-experiment equation of state and phase diagram of each phase of gadolinium is presented for the range of 0 - 10 GPa and 300 - 650 K.« less

Stereoselective HDAC inhibition from cysteine-derived zinc-binding groups.

PubMed

Butler, Kyle V; He, Rong; McLaughlin, Kathryn; Vistoli, Giulio; Langley, Brett; Kozikowski, Alan P

2009-08-01

A series of small-molecule histone deacetylase (HDAC) inhibitors, which feature zinc binding groups derived from cysteine, were synthesized. These inhibitors were tested against multiple HDAC isoforms, and the most potent, compound 10, was determined to have IC(50) values below 1 microM. The compounds were also tested in a cellular assay of oxidative stress-induced neurodegeneration. Many of the inhibitors gave near-complete protection against cell death at 10 microM without the neurotoxicity seen with hydroxamic acid-based inhibitors, and were far more neuroprotective than HDAC inhibitors currently in clinical trials. Both enantiomers of cysteine were used in the synthesis of a variety of novel zinc-binding groups (ZBGs). Derivatives of L-cysteine were active in the HDAC inhibition assays, while the derivatives of D-cysteine were inactive. Notably, the finding that both the D- and L-cysteine derivatives were active in the neuroprotection assays suggests that multiple mechanisms are working to protect the neurons from cell death. Molecular modeling was employed to investigate the differences in inhibitory activity between the HDAC inhibitors generated from the two enantiomeric forms of cysteine.

Hybrid Calcium Phosphate-Polymeric Micelles Incorporating Gadolinium Chelates for Imaging-Guided Gadolinium Neutron Capture Tumor Therapy.

PubMed

Mi, Peng; Dewi, Novriana; Yanagie, Hironobu; Kokuryo, Daisuke; Suzuki, Minoru; Sakurai, Yoshinori; Li, Yanmin; Aoki, Ichio; Ono, Koji; Takahashi, Hiroyuki; Cabral, Horacio; Nishiyama, Nobuhiro; Kataoka, Kazunori

2015-06-23

Gadolinium (Gd) chelates-loaded nanocarriers have high potential for achieving magnetic resonance imaging (MRI)-guided Gd neutron capture therapy (GdNCT) of tumors. Herein, we developed calcium phosphate micelles hybridized with PEG-polyanion block copolymers, and incorporated with the clinical MRI contrast agent Gd-diethylenetriaminepentaacetic acid (Gd-DTPA/CaP). The Gd-DTPA/CaP were nontoxic to cancer cells at the concentration of 100 μM based on Gd-DTPA, while over 50% of the cancer cells were killed by thermal neutron irradiation at this concentration. Moreover, the Gd-DTPA/CaP showed a dramatically increased accumulation of Gd-DTPA in tumors, leading to the selective contrast enhancement of tumor tissues for precise tumor location by MRI. The enhanced tumor-to-blood distribution ratio of Gd-DTPA/CaP resulted in the effective suppression of tumor growth without loss of body weight, indicating the potential of Gd-DTPA/CaP for safe cancer treatment.

Are gadolinium contrast agents suitable for gadolinium neutron capture therapy?

PubMed

De Stasio, Gelsomina; Rajesh, Deepika; Casalbore, Patrizia; Daniels, Matthew J; Erhardt, Robert J; Frazer, Bradley H; Wiese, Lisa M; Richter, Katherine L; Sonderegger, Brandon R; Gilbert, Benjamin; Schaub, Sebastien; Cannara, Rachel J; Crawford, John F; Gilles, Mary K; Tyliszczak, Tolek; Fowler, John F; Larocca, Luigi M; Howard, Steven P; Mercanti, Delio; Mehta, Minesh P; Pallini, Roberto

2005-06-01

Gadolinium neutron capture therapy (GdNCT) is a potential treatment for malignant tumors based on two steps: (1) injection of a tumor-specific (157)Gd compound; (2) tumor irradiation with thermal neutrons. The GdNC reaction can induce cell death provided that Gd is proximate to DNA. Here, we studied the nuclear uptake of Gd by glioblastoma (GBM) tumor cells after treatment with two Gd compounds commonly used for magnetic resonance imaging, to evaluate their potential as GdNCT agents. Using synchrotron X-ray spectromicroscopy, we analyzed the Gd distribution at the subcellular level in: (1) human cultured GBM cells exposed to Gd-DTPA or Gd-DOTA for 0-72 hours; (2) intracerebrally implanted C6 glioma tumors in rats injected with one or two doses of Gd-DOTA, and (3) tumor samples from GBM patients injected with Gd-DTPA. In cell cultures, Gd-DTPA and Gd-DOTA were found in 84% and 56% of the cell nuclei, respectively. In rat tumors, Gd penetrated the nuclei of 47% and 85% of the tumor cells, after single and double injection of Gd-DOTA, respectively. In contrast, in human GBM tumors 6.1% of the cell nuclei contained Gd-DTPA. Efficacy of Gd-DTPA and Gd-DOTA as GdNCT agents is predicted to be low, due to the insufficient number of tumor cell nuclei incorporating Gd. Although multiple administration schedules in vivo might induce Gd penetration into more tumor cell nuclei, a search for new Gd compounds with higher nuclear affinity is warranted before planning GdNCT in animal models or clinical trials.

Reaction of gadolinium chelates with ozone and hydroxyl radicals.

PubMed

Cyris, Maike; Knolle, Wolfgang; Richard, Jessica; Dopp, Elke; von Sonntag, Clemens; Schmidt, Torsten C

2013-09-03

Gadolinium chelates are used in increasing amounts as contrast agents in magnetic resonance imaging, and their fate in wastewater treatment has recently become the focus of research. Oxidative processes, in particular the application of ozone, are currently discussed or even implemented for advanced wastewater treatment. However, reactions of the gadolinium chelates with ozone are not yet characterized. In this study, therefore, rate constants with ozone were determined for the three commonly used chelates Gd-DTPA, Gd-DTPA-BMA, and Gd-BT-DO3A, which were found to be 4.8 ± 0.88, 46 ± 2.5, and 24 ± 1.5 M(-1) s(-1), respectively. These low rate constants indicate that a direct reaction with ozone in wastewater is negligible. However, application of ozone in wastewater leads to substantial yields of (•)OH. Different methods have been applied and compared for determination of k((•)OH+Gd chelate). From rate constants determined by pulse radiolysis experiments (k((•)OH+Gd-DTPA) = 2.6 ± 0.2 × 10(9) M(-1) s(-1), k((•)OH+Gd-DTPA-BMA) = 1.9 ± 0.7 × 10(9) M(-1) s(-1), k((•)OH+Gd-BT-DO3A) = 4.3 ± 0.2 × 10(9) M(-1) s(-1)), it is concluded that a reaction in wastewater via (•)OH radicals is feasible. Toxicity has been tested for educt and product mixtures of both reactions. Cytotoxicity (MTT test) and genotoxicity (micronuclei assay) were not detectable.

Metabolomic Analysis of N-acetylcysteine Protection of Injury from Gadolinium-DTPA Contrast Agent in Rats with Chronic Renal Failure.

PubMed

Wan, Chuanling; Xue, Rong; Zhan, Youyang; Wu, Yijie; Li, Xiaojing; Pei, Fengkui

2017-09-01

Gadolinium-based contrast agents (GBCAs) are frequently used to enhance the diagnostic efficacy of magnetic resonance imaging. On the other hand, the association between GBCA administration in patients with advanced renal disease and nephrogenic systemic fibrosis (NSF) was also noted. NSF is a systemic disorder characterized by widespread tissue fibrosis that may lead to death. N-acetylcysteine (NAC) protects rats from injury induced by gadolinium-based contrast agents, but the underlying mechanisms remain unclear. In this study, a nuclear magnetic resonance-based metabolomic approach was used to systematically investigate the protective effects of NAC on Gd-DTPA-induced injury. Thirty-two male Sprague-Dawley rats were given adenine (200 mg·kg -1 body weight) by oral gavage once a day for 3 weeks to induce chronic renal failure (CRF). NAC (600 mg/L in drinking water for 9 days) pretreatment was initiated 2 days before Gd-DTPA injection (a single tail vein injection, 2 mmol/kg body weight). Serum and liver samples were collected on day 7 after Gd-DTPA injection. By study design, the serum and hepatic metabolic changes of rats were measured in four groups of eight each: CRF, CRF-Gd, CRF-Gd-NAC, and CRF-NAC. Gd-DTPA administration to rats with CRF resulted in disturbances of several metabolic pathways, including glucose, lipid, glutamate, choline, gut microbiota, one-carbon, and purine metabolism. NAC pretreatment reversed the abundance changes of high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, glutamate, glutamine, oxidized glutathione, choline, phosphocholine, glycerophosphocholine, trimethylamine, and trimethylamine-N-oxide induced by Gd-DTPA. It is noteworthy, however, that the ameliorating effects of NAC on the disturbance of glutamate, choline, and gut microbiota metabolism may be specific to Gd-DTPA. In all, these findings could be potentially useful to decipher the underlying mechanisms of NAC protective effects from the

Neuroprotective effect of gadolinium: a stretch-activated calcium channel blocker in mouse model of ischemia-reperfusion injury.

PubMed

Gulati, Puja; Muthuraman, Arunachalam; Jaggi, Amteshwar S; Singh, Nirmal

2013-03-01

The present study was designed to investigate the potential of gadolinium, a stretch-activated calcium channel blocker in ischemic reperfusion (I/R)-induced brain injury in mice. Bilateral carotid artery occlusion of 12 min followed by reperfusion for 24 h was given to induce cerebral injury in male Swiss mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using Morris water maze test and motor incoordination was evaluated using rota-rod, lateral push, and inclined beam walking tests. In addition, total calcium, thiobarbituric acid reactive substance (TBARS), reduced glutathione (GSH), and acetylcholinesterase (AChE) activity were also estimated in brain tissue. I/R injury produced a significant increase in cerebral infarct size. A significant loss of memory along with impairment of motor performance was also noted. Furthermore, I/R injury also produced a significant increase in levels of TBARS, total calcium, AChE activity, and a decrease in GSH levels. Pretreatment of gadolinium significantly attenuated I/R-induced infarct size, behavioral and biochemical changes. On the basis of the present findings, we can suggest that opening of stretch-activated calcium channel may play a critical role in ischemic reperfusion-induced brain injury and that gadolinium has neuroprotective potential in I/R-induced injury.

Analytical Interference in Serum Iron Determination Reveals Iron Versus Gadolinium Transmetallation With Linear Gadolinium-Based Contrast Agents

PubMed Central

Fretellier, Nathalie; Poteau, Nathalie; Factor, Cécile; Mayer, Jean-François; Medina, Christelle; Port, Marc; Idée, Jean-Marc; Corot, Claire

2014-01-01

Objectives The purposes of this study were to evaluate the risk for analytical interference with gadolinium-based contrast agents (GBCAs) for the colorimetric measurement of serum iron (Fe3+) and to investigate the mechanisms involved. Materials and Methods Rat serum was spiked with several concentrations of all molecular categories of GBCAs, ligands, or “free” soluble gadolinium (Gd3+). Serum iron concentration was determined by 2 different colorimetric methods at pH 4.0 (with a Vitros DT60 analyzer or a Cobas Integra 400 analyzer). Secondly, the cause of interference was investigated by (a) adding free soluble Gd3+ or Mn2+ to serum in the presence of gadobenic acid or gadodiamide and (b) electrospray ionization mass spectrometry. Results Spurious decrease in serum Fe3+ concentration was observed with all linear GBCAs (only with the Vitros DT60 technique occurring at pH 4.0) but not with macrocyclic GBCAs or with free soluble Gd3+. Spurious hyposideremia was also observed with the free ligands present in the pharmaceutical solutions of the linear GBCAs gadopentetic acid and gadodiamide (ie, diethylene triamine pentaacetic acid and calcium-diethylene triamine pentaacetic acid bismethylamide, respectively), suggesting the formation of Fe-ligand chelate. Gadobenic acid-induced interference was blocked in a concentration-dependent fashion by adding a free soluble Gd3+ salt. Conversely, Mn2+, which has a lower affinity than Gd3+ and Fe3+ for the ligand of gadobenic acid (ie, benzyloxypropionic diethylenetriamine tetraacetic acid), was less effective (interference was only partially blocked), suggesting an Fe3+ versus Gd3+ transmetallation phenomenon at pH 4.0. Similar results were observed with gadodiamide. Mass spectrometry detected the formation of Fe-ligand with all linear GBCAs tested in the presence of Fe3+ and the disappearance of Fe-ligand after the addition of free soluble Gd3+. No Fe-ligand chelate was found in the case of the macrocyclic GBCA gadoteric

Stability of Gadolinium-Doped Liquid Organic Scintillators

NASA Astrophysics Data System (ADS)

Gromov, M. B.; Kuznetsov, D. S.; Murchenko, A. E.; Novikova, G. Ya.; Obinyakov, B. A.; Oralbaev, A. Yu.; Plakitina, K. V.; Skorokhvatov, M. D.; Sukhotin, S. V.; Chepurnov, A. S.; Etenko, A. V.

2018-03-01

The technology of preparing a linear-alkylbenzene-based gadolinium-doped liquid organic scintillator (Gd-LOS) as a target material in reactor antineutrino detectors has been developed. Results of longterm measurements of the light yield of Gd-LOS in contact with acryl and stainless steel are presented, which confirm the compatibility of Gd-LOS with these materials. The measurements were performed for two otherwise identical LOS detectors only differing in wall materials of the sensitive volume: acryl versus stainless steel. The results of measurements over about one year showed almost the same, relatively small decreases in the light yield of both detectors. It is concluded that both structural materials can be used in detector parts contacting with Gd-doped scintillator. Such a long-term parallel comparative test was carried out for the first time.

Analysis of Blood Gadolinium in an Isotope Geochemist Following Contrast MRI

NASA Astrophysics Data System (ADS)

Wasylenki, L. E.

2011-12-01

Normal brain tissue does not have blood flowing throughout it; instead oxygen diffuses across a blood-brain barrier in order to oxygenate brain cells. Brain tumors, however, do grow blood supplies, so an abnormal distribution of blood in the brain is a key indicator of abnormal cell growth. But how is the distribution of blood in inside the brain observed? The lanthanide ion gadolinium(III) has unpaired 5f-shell electrons and is thus paramagnetic. As such, the presence of Gd causes the nuclei of nearby atoms to relax more quickly when excited to high-energy spin states by pulses of radio-frequency energy than they would without Gd nearby. The signal in magnetic resonance imaging correlates with this nuclear spin relaxation time, so gadolinium's presence in certain body tissues makes those tissues appear as bright areas on MRI images. Gadolinium is therefore commonly injected intravenously just prior to MRI imaging, so that the distribution of blood in and around the brain can be mapped. Gadolinium as a free ion is toxic, so it is injected in a relatively inert form, often as gadoversetamide, in which Gd is tightly bound in nine-fold coordination with N, C, and O. This compound is removed from the blood by the kidneys at a rate that is fast compared to the rate of breakdown of this compound in the blood, thus preventing release of toxic Gd in the bloodstream. But how quickly can the kidneys of an isotope geochemist remove Gd from blood? In this experiment, a single isotope geochemist's wristwatch was synchronized with that of the MRI technician and then left in a dressing room with all other magnetically susceptible objects until after the MRI. The time of intravenous injection of gadoversetamide into the isotopist was recorded by the technician and later transmitted verbally to the isotopist. Following the MRI session, blood samples were collected by self-fingerprick, in a Class 100 trace metal clean lab, from 47 to 281 minutes after intravenous injection. For each

N-(4-Trifluoromethylphenyl)amide group of the synthetic histamine receptor agonist inhibits nicotinic acetylcholine receptor-mediated catecholamine secretion.

PubMed

Kim, Dong-Chan; Park, Yong-Soo; Jun, Dong-Jae; Hur, Eun-Mi; Kim, Sun-Hee; Choi, Bo-Hwa; Kim, Kyong-Tai

2006-02-28

The therapeutic targeting of nicotinic receptors requires the identification of drugs that selectively activate or inhibit a limited range of nicotine acetylcholine receptors (nAChRs). In this study, we identified N-(4-trifluoromethylphenyl)amide group of the synthetic histamine receptor ligands, histamine-trifluoromethyltoluide, that act as potent inhibitors of nAChRs in bovine adrenal chromaffin cells. Catecholamine secretion induced by the nAChRs agonist, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), was significantly inhibited by histamine-trifluoromethyltoluide. Real time carbon-fiber amperometry confirmed the ability of histamine-trifluoromethyltoluide to inhibit DMPP-induced exocytosis in single chromaffin cells. We also found that histamine-trifluoromethyltoluide inhibited DMPP-induced [Ca(2+)](i) and [Na(+)](i) increases, as well as DMPP-induced inward currents in the absence of extracellular calcium. Histamine-trifluoromethyltoluide had no effect on [(3)H]nicotine binding or on calcium increases induced by high K(+), bradykinin, veratridine, histamine, and benzoylbenzoyl ATP. Among the synthetic histamine receptor ligands, clobenpropit exhibited similarity. In addition, 4'-nitroacetanilide also significantly attenuated nAChR-mediated catecholamine secretion. In conclusion, the N-(4-trifluoromethylphenyl)amide group of the histamine-trifluoromethyltoluide might be the critical moiety in the inhibition of nAChR-mediated CA secretion.

Teachers' Promotion or Inhibition of Children's Aggression Depends on Peer-Group Characteristics.

PubMed

Peets, Kätlin; Kikas, Eve

2017-01-01

Researchers have increasingly started to pay attention to how contextual factors, such as the classroom peer context and the quality of student-teacher interactions, influence children's aggressive behavior. This longitudinal study was designed to examine the degree to which benefits and costs of different teaching practices (child-centered and child-dominated) would be dependent on the initial peer-group composition (aggregate levels of aggression and victimization at the beginning of first grade). Teachers provided ratings of aggression and victimization (N = 523 first-grade students; M age at the beginning of first grade = 7.49 years, SD = 0.52). Information about different teaching practices was obtained via observations. Our results show that whereas child-centered practices are beneficial in high-victimization classrooms, child-dominated practices inhibit the development of aggression in low-victimization classroom contexts. Our findings highlight the importance of moving beyond main-effect models to studying how different contextual influences interact to promote, or inhibit, the development of aggression.

Dramatic impact of the giant local magnetic fields on spin-dependent recombination processes in gadolinium based garnets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Romanov, N. G., E-mail: nikolai.romanov@mail.ioffe.ru; Tolmachev, D. O.; Gurin, A. S.

2015-06-29

A giant magnetic field effect on spin-dependent recombination of the radiation-induced defects has been found in cerium doped gadolinium based garnet crystals and ceramics, promising materials for scintillator applications. A sharp and strong increase in the afterglow intensity stimulated by external magnetic field and an evidence of the magnetic field memory have been discovered. The effect was ascribed to huge Gd-induced internal magnetic fields, which suppress the recombination, and cross-relaxation with Gd{sup 3+} ions leading to reorientation of the spins of the electron and hole centers. Thus, the spin system of radiation-induced defects in gadolinium garnet based scintillator materials wasmore » shown to accumulate significant energy which can be released in external magnetic fields.« less

The effect of various zinc binding groups on inhibition of histone deacetylases 1-11.

PubMed

Madsen, Andreas S; Kristensen, Helle M E; Lanz, Gyrithe; Olsen, Christian A

2014-03-01

Histone deacetylases (HDACs) have the ability to cleave the acetyl groups of ε-N-acetylated lysine residues in a variety of proteins. Given that human cells contain thousands of different acetylated lysine residues, HDACS may regulate a wide variety of processes including some implicated in conditions such as cancer and neurodegenerative disorders. Herein we report the synthesis and in vitro biochemical profiling of a series of compounds, including known inhibitors as well as novel chemotypes, that incorporate putative new zinc binding domains. By evaluating the compound collection against all 11 recombinant human HDACs, we found that the trifluoromethyl ketone functionality provides potent inhibition of all four subclasses of the Zn(2+) -dependent HDACs. Potent inhibition was observed with two different scaffolds, demonstrating the efficiency of the trifluoromethyl ketone moiety as a zinc binding motif. Interestingly, we also identified silanediol as a zinc binding group with potential for future development of non-hydroxamate class I and class IIb HDAC inhibitors. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gadolinium enhanced cardiovascular magnetic resonance in Anderson-Fabry disease. Evidence for a disease specific abnormality of the myocardial interstitium.

PubMed

Moon, James C C; Sachdev, Bhavesh; Elkington, Andrew G; McKenna, William J; Mehta, Atul; Pennell, Dudley J; Leed, Philip J; Elliott, Perry M

2003-12-01

Anderson-Fabry Disease (AFD), an X-linked disorder of sphingolipid metabolism, is a cause of idiopathic left ventricular hypertrophy but the mechanism of hypertrophy is poorly understood. Gadolinium enhanced cardiovascular magnetic resonance can detect focal myocardial fibrosis. We hypothesised that hyperenhancement would be present in AFD. Eighteen males (mean 43+/-14 years) and eight female heterozygotes (mean 48+/-12 years) with AFD underwent cine and late gadolinium cardiovascular magnetic resonance. Nine male (50%) had myocardial hyperenhancement ranging from 3.4% to 20.6% (mean 7.7+/-5.7%) of total myocardium; in males, percentage hyperenhancement related to LV mass index (r=0.78, P=0.0002) but not to ejection fraction or left ventricular volumes. Lesser hyperenhancement was also found in four (50%) heterozygous females (mean 4.6%). In 12 (92%) patients with abnormal gadolinium uptake, hyperenhancement occurred in the basal infero-lateral wall where, unlike myocardial infarction, it was not sub-endocardial. In two male patients with severe LVH (left ventricular hypertrophy) and systolic impairment there was additional hyperenhancement in other myocardial segments. These observations suggests that myocardial fibrosis occurs in AFD and may contribute to the hypertrophy and the natural history of the disease.

Electrical and Structural Substrate of Arrhythmogenic Right Ventricular Cardiomyopathy Determined Using Noninvasive Electrocardiographic Imaging and Late Gadolinium Magnetic Resonance Imaging.

PubMed

Andrews, Christopher M; Srinivasan, Neil T; Rosmini, Stefania; Bulluck, Heerajnarain; Orini, Michele; Jenkins, Sharon; Pantazis, Antonis; McKenna, William J; Moon, James C; Lambiase, Pier D; Rudy, Yoram

2017-07-01

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a significant cause of sudden cardiac death in the young. Improved noninvasive assessment of ARVC and better understanding of the disease substrate are important for improving patient outcomes. We studied 20 genotyped ARVC patients with a broad spectrum of disease using electrocardiographic imaging (a method for noninvasive cardiac electrophysiology mapping) and advanced late gadolinium enhancement cardiac magnetic resonance scar imaging. Compared with 20 healthy controls, ARVC patients had longer ventricular activation duration (median, 52 versus 42 ms; P =0.007) and prolonged mean epicardial activation-recovery intervals (a surrogate for local action potential duration; median, 275 versus 241 ms; P =0.014). In these patients, we observed abnormal and varied epicardial activation breakthrough locations and regions of nonuniform conduction and fractionated electrograms. Nonuniform conduction and fractionated electrograms were present in the early concealed phase of ARVC. Electrophysiological abnormalities colocalized with late gadolinium enhancement scar, indicating a relationship with structural disease. Premature ventricular contractions were common in ARVC patients with variable initiation sites in both ventricles. Premature ventricular contraction rate increased with exercise, and within anatomic segments, it correlated with prolonged repolarization, electric markers of scar, and late gadolinium enhancement (all P <0.001). Electrocardiographic imaging reveals electrophysiological substrate properties that differ in ARVC patients compared with healthy controls. A novel mechanistic finding is the presence of repolarization abnormalities in regions where ventricular ectopy originates. The results suggest a potential role for electrocardiographic imaging and late gadolinium enhancement in early diagnosis and noninvasive follow-up of ARVC patients. © 2017 American Heart Association, Inc.

Switching of the polarization of ferroelectric-ferroelastic gadolinium molybdate in a magnetic field

NASA Astrophysics Data System (ADS)

Yakushkin, E. D.

2017-10-01

A change in the character of the electric switching of polydomain ferroelectric-ferroelastic gadolinium molybdate in an external magnetic field has been detected. This change has been attributed to a magnetically stimulated increase in the pinning of domain walls. Under certain conditions, the loop of switchable polarization is degenerated into an ellipse characteristic of a linear insulator with leakage current.

Neurosarcoidosis--demonstration of meningeal disease by gadolinium enhanced magnetic resonance imaging.

PubMed Central

Khaw, K T; Manji, H; Britton, J; Schon, F

1991-01-01

Arriving at a firm diagnosis of neurosarcoidosis continues to pose serious problems, particularly when evidence of granulomatous disease outside the nervous system is lacking. The commonest mode of presentation of neurosarcoidosis is with cranial nerve palsies. Two cases of presumed neurosarcoidosis with cranial nerve palsies showed clear evidence of focal meningeal disease on gadolinium-DTPA enhanced MRI brain scans. Although not specific for sarcoidosis, this technique may be very useful in aiding the diagnosis in suspected cases. Images PMID:1880510

Gadolinium-modulated 19F signals from Perfluorocarbon Nanoparticles as a New Strategy for Molecular Imaging

PubMed Central

Neubauer, Anne M.; Myerson, Jacob; Caruthers, Shelton D.; Hockett, Franklin D.; Winter, Patrick M.; Chen, Junjie; Gaffney, Patrick J.; Robertson, J. David; Lanza, Gregory M.; Wickline, Samuel A.

2008-01-01

Recent advances in the design of fluorinated nanoparticles for magnetic resonance molecular imaging have enabled specific detection of 19F nuclei, providing unique and quantifiable spectral signatures. However, a pressing need for signal enhancement exists because the total 19F in imaging voxels is often limited. By directly incorporating a relaxation agent (gadolinium) into the lipid monolayer that surrounds the perfluorocarbon, a marked augmentation of the 19F signal from 200nm nanoparticles was achieved. This design increases the magnetic relaxation rate of the 19F nuclei 4-fold at 1.5 T and effects a 125% increase in signal, an effect which is maintained when they are targeted to human plasma clots. By varying the surface concentration of gadolinium, the relaxation effect can be quantitatively modulated to tailor particle properties. This novel strategy dramatically improves the sensitivity and range of 19F MRI/MRS and forms the basis for designing contrast agents capable of sensing their surface chemistry. PMID:18956457

Right ventricular stress-induced perfusion defects and late gadolinium enhancement in coronary artery disease.

PubMed

Milks, Michael Wesley; Upadhya, Bharathi; Hall, Michael E; Vasu, Sujethra; Hundley, William Gregory; Stacey, Richard Brandon

2015-01-01

The assessment of right ventricular (RV) perfusion defects has remained challenging during vasodilator stress perfusion with cardiovascular magnetic resonance (CMR). The significance of RV signal abnormalities during vasodilator stress perfusion and late gadolinium-enhanced CMR is yet uncertain. Among 61 individuals who underwent adenosine CMR stress testing before cardiac catheterization, we assessed the severity of coronary artery stenoses, mortality, the presence of stress and rest perfusion defects, as well as the presence of late gadolinium enhancement (LGE). Right ventricular stress-induced perfusion defects were positively associated with left anterior descending artery and proximal right coronary artery stenoses but were negatively associated with left circumflex artery stenoses. The presence of RVLGE was associated with mortality, but 77% of those with RVLGE also had left ventricular LGE. Proximal right coronary artery and left anterior descending artery stenoses are positively associated, whereas left circumflex artery stenoses are negatively associated with RV stress-induced perfusion defects. Right ventricular LGE was associated with mortality, but further study is needed to determine whether this is independent of left ventricular LGE.

Effect of solid-phase amorphization on the spectral characteristics of europium-doped gadolinium molybdate

NASA Astrophysics Data System (ADS)

Shmurak, S. Z.; Kiselev, A. P.; Kurmasheva, D. M.; Red'Kin, B. S.; Sinitsyn, V. V.

2010-05-01

A method is proposed for detecting spectral characteristics of optically inactive molybdates of rare-earth elements by their doping with rare-earth ions whose luminescence lies in the transparency region of all structural modifications of the sample. Gadolinium molybdate is chosen as the object of investigations, while europium ions are used as an optically active and structurally sensitive admixture. It is shown that after the action of a high pressure under which gadolinium molybdate passes to the amorphous state, the spectral characteristics of Gd1.99Eu0.01(MoO4)3 (GMO:Eu) change radically; namely, considerable line broadening is observed in the luminescence spectra and the luminescence excitation spectra, while the long-wave threshold of optical absorption is shifted considerably (by approximately 1.1 eV) towards lower energies. It is found that by changing the structural state of GMO:Eu by solid-state amorphization followed by annealing, the spectral characteristics of the sample can be purposefully changed. This is extremely important for solving the urgent problem of designing high-efficiency light-emitting diodes producing “white” light.

Graphene oxide-gadolinium (III) oxide nanoparticle composite: a novel MR contrast agent with high longitudinal and transverse relaxivity

NASA Astrophysics Data System (ADS)

Venkatesha, N.; Poojar, Pavan; Geethanath, Sairam; Srivastava, Chandan

2014-12-01

Production of bio-compatible contrast agent materials to enhance the sensitivity of the magnetic resonance imaging (MRI) technique is a highly active area in MRI related research. This work illustrates the potential of a new material: graphene oxide-gadolinium (III) oxide nanoparticle (GO-Gd2O3) composite in yielding both transverse (16.3 mM-1 s-1) and longitudinal relaxivity (40 mM-1 s-1) values which are significantly higher than the proton relaxivity values achieved using the gadolinium based contrast agents currently used in MRI. Such high proton relaxivity values can facilitate low dosage of GO-Gd2O3 composite for obtaining both T1 and T2 weighted high signal-to-noise ratio images in MRI.

A comparison of the COG and MCNP codes in computational neutron capture therapy modeling, Part II: gadolinium neutron capture therapy models and therapeutic effects.

PubMed

Wangerin, K; Culbertson, C N; Jevremovic, T

2005-08-01

The goal of this study was to evaluate the COG Monte Carlo radiation transport code, developed and tested by Lawrence Livermore National Laboratory, for gadolinium neutron capture therapy (GdNCT) related modeling. The validity of COG NCT model has been established for this model, and here the calculation was extended to analyze the effect of various gadolinium concentrations on dose distribution and cell-kill effect of the GdNCT modality and to determine the optimum therapeutic conditions for treating brain cancers. The computational results were compared with the widely used MCNP code. The differences between the COG and MCNP predictions were generally small and suggest that the COG code can be applied to similar research problems in NCT. Results for this study also showed that a concentration of 100 ppm gadolinium in the tumor was most beneficial when using an epithermal neutron beam.

Gadolinium chloride as a contrast agent for imaging wood composite components by magnetic resonance

Treesearch

Thomas L. Eberhardt; Chi-Leung So; Andrea Protti; Po-Wah So

2009-01-01

Although paramagnetic contrast agents have an established track record in medical uses of magnetic resonance imaging (MRI), only recently has a contrast agent been used for enhancing MRI images of solid wood specimens. Expanding on this concept, wood veneers were treated with a gadolinium-based contrast agent and used in a model system comprising three-ply plywood...

Comparison of gadolinium-EOB-DTPA-enhanced and diffusion-weighted liver MRI for detection of small hepatic metastases.

PubMed

Shimada, Kotaro; Isoda, Hiroyoshi; Hirokawa, Yuusuke; Arizono, Shigeki; Shibata, Toshiya; Togashi, Kaori

2010-11-01

To compare the accuracy of gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI with that of diffusion-weighted MRI (DWI) in the detection of small hepatic metastases (2 cm or smaller). Forty-five patients underwent abdominal MRI at 3 T, including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), heavily T2WI (HASTE), DWI with a b-value of 500 s/mm(2) and contrast-enhanced MRI with Gd-EOB-DTPA. Two groups were assigned and compared: group A (T1WI, T2WI, HASTE and contrast-enhanced study with Gd-EOB-DTPA), and group B (T1WI, T2WI, HASTE and DWI). Two observers independently interpreted the images obtained in a random order. For all hepatic metastases, the diagnostic performance using each imaging set was evaluated by receiver-operating characteristic (ROC) curve analysis. A total of 51 hepatic metastases were confirmed. The area under the ROC curve (Az) of group A was larger than that of group B, and the difference in the mean Az values between the two image sets was statistically significant, whereas, there were three metastases that lay near thin vessels or among multiple cysts and were better visualised in group B than in group A. Gd-EOB-DTPA-enhanced MRI showed higher accuracy in the detection of small metastases than DWI.

Use of gadolinium chloride as a contrast agent for imaging spruce knots by magnetic resonance

Treesearch

Thomas L. Eberhardt; Chi-Leung So; Amy H. Herlihy; Po-Wah So

2006-01-01

Treatments of knot-containing spruce wood blocks with a paramagnetic salt, gadolinium (III) chloride, in combination with solvent pretreatments, were evaluated as strategies to enhance the visualization of wood features by magnetic resonance imaging (MRI). Initial experiments with clear wood and excised knot samples showed differences in moisture uptake after...

Strategies for the preparation of bifunctional gadolinium(III) chelators

PubMed Central

Frullano, Luca; Caravan, Peter

2012-01-01

The development of gadolinium chelators that can be easily and readily linked to various substrates is of primary importance for the development high relaxation efficiency and/or targeted magnetic resonance imaging (MRI) contrast agents. Over the last 25 years a large number of bifunctional chelators have been prepared. For the most part, these compounds are based on ligands that are already used in clinically approved contrast agents. More recently, new bifunctional chelators have been reported based on complexes that show a more potent relaxation effect, faster complexation kinetics and in some cases simpler synthetic procedures. This review provides an overview of the synthetic strategies used for the preparation of bifunctional chelators for MRI applications. PMID:22375102

SWI enhances vein detection using gadolinium in multiple sclerosis

PubMed Central

Mazzoni, Lorenzo N; Moretti, Marco; Grammatico, Matteo; Chiti, Stefano; Massacesi, Luca

2015-01-01

Susceptibility weighted imaging (SWI) combined with the FLAIR sequence provides the ability to depict in vivo the perivenous location of inflammatory demyelinating lesions – one of the most specific pathologic features of multiple sclerosis (MS). In addition, in MS white matter (WM) lesions, gadolinium-based contrast media (CM) can increase vein signal loss on SWI. This report focuses on two cases of WM inflammatory lesions enhancing on SWI images after CM injection. In these lesions in fact the CM increased the contrast between the parenchyma and the central vein allowing as well, in one of the two cases, the detection of a vein not visible on the same SWI sequence acquired before CM injection. PMID:25815209

Group III metabotropic glutamate receptors and exocytosed protons inhibit L-type calcium currents in cones but not in rods.

PubMed

Hosoi, Nobutake; Arai, Itaru; Tachibana, Masao

2005-04-20

Light responses of photoreceptors (rods and cones) are transmitted to the second-order neurons (bipolar cells and horizontal cells) via glutamatergic synapses located in the outer plexiform layer of the retina. Although it has been well established that postsynaptic group III metabotropic glutamate receptors (mGluRs) of ON bipolar cells contribute to generating the ON signal, presynaptic roles of group III mGluRs remain to be elucidated at this synaptic connection. We addressed this issue by applying the slice patch-clamp technique to the newt retina. OFF bipolar cells and horizontal cells generate a steady inward current in the dark and a transient inward current at light offset, both of which are mediated via postsynaptic non-NMDA receptors. A group III mGluR-specific agonist, L-2-amino-4-phosphonobutyric acid (L-AP-4), inhibited both the steady and off-transient inward currents but did not affect the glutamate-induced current in these postsynaptic neurons. L-AP-4 inhibited the presynaptic L-type calcium current (ICa) in cones by shifting the voltage dependence of activation to more positive membrane potentials. The inhibition of ICa was most prominent around the physiological range of cone membrane potentials. In contrast, L-AP-4 did not affect L-type ICa in rods. Paired recordings from photoreceptors and the synaptically connected second-order neurons confirmed that L-AP-4 inhibited both ICa and glutamate release in cones but not in rods. Furthermore, we found that exocytosed protons also inhibited ICa in cones but not in rods. Selective modulation of ICa in cones may help broaden the dynamic range of synaptic transfer by controlling the amount of transmitter release from cones.

The structural response of gadolinium phosphate to pressure

DOE PAGES

Heffernan, Karina M.; Ross, Nancy L.; Spencer, Elinor C.; ...

2016-06-16

In this study, accurate elastic constants for gadolinium phosphate (GdPO 4) have been measured by single-crystal high-pressure diffraction methods. The bulk modulus of GdPO 4 determined under hydrostatic conditions, 128.1(8) GPa (K'=5.8(2)), is markedly different from that obtained with GdPO 4 under non-hydrostatic conditions (160(2) GPa), which indicates the importance of shear stresses on the elastic response of this phosphate. Finally, high pressure Raman and diffraction analysis indicate that the PO 4 tetrahedra behave as rigid units in response to pressure and that contraction of the GdPO 4 structure is facilitated by bending/twisting of the Gd–O–P links that result inmore » increased distortion in the GdO 9 polyhedra.« less

Dielectric properties and activation behavior of gadolinium doped nanocrystalline yttrium chromite

NASA Astrophysics Data System (ADS)

Sinha, R.; Basu, S.; Meikap, A. K.

2018-04-01

Gadolinium doped Yttrium Chromite nanoparticles are synthesized following sol-gel method. The formation of the nanoparticles are confirmed by XRD and TEM measurements. Dielectric permittivity and dielectric loss are estimated within the temperature range 298K to 523K and in the frequency range 20 Hz to 1 MHz. Dielectric permittivity follows the power law ɛ'(f) ∝ Tm. It is observed that the temperature exponent m increases with the decreasing frequency. The temperature variation of resistivity shows that the samples have semiconducting behavior. The activation energy is also measured.

Preparation of 152Gd targets from a small quantity of gadolinium oxide in a pyrochemical reaction

NASA Astrophysics Data System (ADS)

Lipski, A. R.

1995-02-01

A simple method utilizing small amounts (< 5 mg) of isotopically enriched material for the production of gadolinium targets is discussed. An electrostatically focused e-gun is used in the procedure in which 152Gd 2O 3 powder undergoes reduction-distillation and deposition onto an Fe foil.

Motexafin-Gadolinium and Involved Field Radiation Therapy for Intrinsic Pontine Glioma of Childhood: A Children's Oncology Group Phase 2 Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bradley, Kristin A., E-mail: bradley@humonc.wisc.edu; Zhou Tianni; McNall-Knapp, Rene Y.

2013-01-01

Purpose: To evaluate the effects on 1-year event-free survival (EFS) and overall survival (OS) of combining motexafin and gadolinium (MGd), a potent radiosensitizer, with daily fractionated radiation therapy in children with newly diagnosed intrinsic pontine gliomas. Methods and Materials: Patients with newly diagnosed intrinsic pontine glioma were treated with MGd daily for 5 consecutive days each week, for a total of 30 doses. Patients received a 5- to 10-min intravenous bolus of MGd, 4.4 mg/kg/day, given 2 to 5 h prior to standard dose irradiation. Radiation therapy was administered at a daily dose of 1.8 Gy for 30 treatments overmore » 6 weeks. The total dose was 54 Gy. Results: Sixty eligible children received MGd daily, concurrent with 6 weeks of radiation therapy. The estimated 1-year EFS was 18% {+-} 5%, and the estimated 1-year OS was 53% {+-} 6.5%. The most common grade 3 to 4 toxicities were lymphopenia, transient elevation of liver transaminases, and hypertension. Conclusions: Compared to historical controls, the addition of MGd to a standard 6-week course of radiation did not improve the survival of pediatric patients with newly diagnosed intrinsic pontine gliomas.« less

Corrosion resistance of 0Kh18N10T steel in gadolinium nitrate solutions in the liquid regulation of the reactivity of nuclear reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganzha, V.D.; Konoplev, K.A.; Mashchetov, V.P.

1986-03-01

This study was carried out in connection with the preparation of the design for the PIK research reactor. The corrosion resistance of 0Kh18N10T steel in gadolinium nitrate solutions was tested in laboratory, ampule, and loop corrosion tests. At all stages of the tests, the authors investigated the effect produced on the corrosion processes by factors related to the technology of preparation of the equipment (mechanical working of the surfaces, welding, sensitizing, annealing, stressed state of the material, cracks, etc.). Ampule tests were conducted in order to determine the effect produced by reactor radiation and shutdown regimes on the corrosion resistancemore » of the steel. Special ampules made of 0Kh18N10T steel were filled with gadolinium nitrate solutions of various concentrations, sealed, and irradiated for a long period in the core of the VVR-M reactor at a temperature of 20-50 degrees C. The results of the tests are shown. The investigations showed that the corrosion of 0Kh18N10T steel in solutions of gadolinium nitrate is uniform, regardless of the state of the surface, the concentration of gadolinium nitrate, the duration of the tests, the action of the reactor radiation under static and dynamic conditions, and the presence of mechanical stresses.« less

Influence of acquired obesity on coronary vessel wall late gadolinium enhancement in discordant monozygote twins.

PubMed

Makowski, Marcus R; Jansen, Christian H P; Ebersberger, Ullrich; Schaeffter, Tobias; Razavi, Reza; Mangino, Massimo; Spector, Tim D; Botnar, Rene M; Greil, Gerald F

2017-11-01

The aim of this study was to investigate the impact of BMI on late gadolinium enhancement (LGE) of the coronary artery wall in identical monozygous twins discordant for BMI. Coronary LGE represents a useful parameter for the detection and quantification of atherosclerotic coronary vessel wall disease. Thirteen monozygote female twin pairs (n = 26) with significantly different BMIs (>1.6 kg/m2) were recruited out of >10,000 twin pairs (TwinsUK Registry). A coronary 3D-T2prep-TFE MR angiogram and 3D-IR-TFE vessel wall scan were performed prior to and following the administration of 0.2 mmol/kg of Gd-DTPA on a 1.5 T MR scanner. The number of enhancing coronary segments and contrast to noise ratios (CNRs) of the coronary wall were quantified. An increase in BMI was associated with an increased number of enhancing coronary segments (5.3 ± 1.5 vs. 3.5 ± 1.6, p < 0.0001) and increased coronary wall enhancement (6.1 ± 1.1 vs. 4.8 ± 0.9, p = 0.0027) compared to matched twins with lower BMI. This study in monozygous twins indicates that acquired factors predisposing to obesity, including lifestyle and environmental factors, result in increased LGE of the coronary arteries, potentially reflecting an increase in coronary atherosclerosis in this female study population. • BMI-discordant twins allow the investigation of the influence of lifestyle factors independent from genetic confounders. • Only thirteen obesity-discordant twins were identified underlining the strong genetic component of BMI. • In female twins, a BMI increase is associated with increased coronary late gadolinium enhancement. • Increased late gadolinium enhancement in the coronary vessel wall potentially reflects increased atherosclerosis.

Synthesis of samarium doped gadolinium oxide nanorods, its spectroscopic and physical properties

NASA Astrophysics Data System (ADS)

Boopathi, G.; Gokul Raj, S.; Ramesh Kumar, G.; Mohan, R.; Mohan, S.

2018-06-01

One-dimensional samarium doped gadolinium oxide [Sm:Gd2O3] nanorods have been synthesized successfully through co-precipitation technique in aqueous solution. The as-synthesized and calcined products were characterized by using powder X-ray diffraction pattern, Fourier transform Raman spectroscopy, thermogravimetric/differential thermal analysis, scanning electron microscopy with energy-dispersive X-ray analysis, transmission electron microscopy, Fourier transform infrared spectroscopy, Ultraviolet-Visible spectrometry, photoluminescence spectrophotometer and X-ray photoelectron spectroscopy techniques. The obtained results are discussed in detailed manner.

Investigation of suspected Guillain-Barre syndrome in childhood: what is the role for gadolinium enhanced magnetic resonance imaging of the spine?

PubMed

Smith, Nicholas; Pereira, John; Grattan-Smith, Padraic

2014-10-01

To review the role of gadolinium-enhanced magnetic resonance imaging of the spine in the diagnosis of paediatric Guillain-Barre syndrome and compare it with nerve conduction studies and cerebrospinal fluid analysis. A retrospective review of investigations undertaken in children admitted to our institution with acute Guillain-Barre syndrome over a 10-year period was performed. Seven of eight children (88%) displayed post-gadolinium nerve root enhancement consistent with Guillain-Barre syndrome. This compared with supportive nerve conduction studies in 21/24 children (88%) and cerebrospinal fluid protein analysis consistent with the diagnosis in 16/20 children (80%). Nerve conduction studies are the recognised 'gold standard' technique for confirming a clinical diagnosis of Guillain-Barre syndrome. In this study, a high positive rate was demonstrated. While more experience is necessary, this study and the literature support gadolinium enhanced magnetic resonance imaging of the spine as a valuable, although not necessarily superior, investigation in the diagnosis of Guillain-Barre syndrome. It may be of particular benefit when specialist neurophysiology expertise is unavailable. © 2010 The Authors. Journal compilation © 2010 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Group II intron inhibits conjugative relaxase expression in bacteria by mRNA targeting

PubMed Central

Piazza, Carol Lyn; Smith, Dorie

2018-01-01

Group II introns are mobile ribozymes that are rare in bacterial genomes, often cohabiting with various mobile elements, and seldom interrupting housekeeping genes. What accounts for this distribution has not been well understood. Here, we demonstrate that Ll.LtrB, the group II intron residing in a relaxase gene on a conjugative plasmid from Lactococcus lactis, inhibits its host gene expression and restrains the naturally cohabiting mobile element from conjugative horizontal transfer. We show that reduction in gene expression is mainly at the mRNA level, and results from the interaction between exon-binding sequences (EBSs) in the intron and intron-binding sequences (IBSs) in the mRNA. The spliced intron targets the relaxase mRNA and reopens ligated exons, causing major mRNA loss. Taken together, this study provides an explanation for the distribution and paucity of group II introns in bacteria, and suggests a potential force for those introns to evolve into spliceosomal introns. PMID:29905149

Group II intron inhibits conjugative relaxase expression in bacteria by mRNA targeting.

PubMed

Qu, Guosheng; Piazza, Carol Lyn; Smith, Dorie; Belfort, Marlene

2018-06-15

Group II introns are mobile ribozymes that are rare in bacterial genomes, often cohabiting with various mobile elements, and seldom interrupting housekeeping genes. What accounts for this distribution has not been well understood. Here, we demonstrate that Ll.LtrB, the group II intron residing in a relaxase gene on a conjugative plasmid from Lactococcus lactis , inhibits its host gene expression and restrains the naturally cohabiting mobile element from conjugative horizontal transfer. We show that reduction in gene expression is mainly at the mRNA level, and results from the interaction between exon-binding sequences (EBSs) in the intron and intron-binding sequences (IBSs) in the mRNA. The spliced intron targets the relaxase mRNA and reopens ligated exons, causing major mRNA loss. Taken together, this study provides an explanation for the distribution and paucity of group II introns in bacteria, and suggests a potential force for those introns to evolve into spliceosomal introns. © 2018, Qu et al.

Removal of gadolinium-based contrast agents: adsorption on activated carbon.

PubMed

Elizalde-González, María P; García-Díaz, Esmeralda; González-Perea, Mario; Mattusch, Jürgen

2017-03-01

Three carbon samples were employed in this work, including commercial (1690 m 2  g -1 ), activated carbon prepared from guava seeds (637 m 2  g -1 ), and activated carbon prepared from avocado kernel (1068 m 2  g -1 ), to study the adsorption of the following gadolinium-based contrast agents (GBCAs): gadoterate meglumine Dotarem®, gadopentetate dimeglumine Magnevist®, and gadoxetate disodium Primovist®. The activation conditions with H 3 PO 4 were optimized using a Taguchi methodology to obtain mesoporous materials. The best removal efficiency by square meter in a batch system in aqueous solution and model urine was achieved by avocado kernel carbon, in which mesoporosity prevails over microporosity. The kinetic adsorption curves were described by a pseudo-second-order equation, and the adsorption isotherms in the concentration range 0.5-6 mM fit the Freundlich equation. The chemical characterization of the surfaces shows that materials with a greater amount of phenolic functional groups adsorb the GBCA better. Adsorption strongly depends on the pH due to the combination of the following factors: contrast agent protonated forms and carbon surface charge. The tested carbon samples were able to adsorb 70-90% of GBCA in aqueous solution and less in model urine. This research proposes a method for the elimination of GBCA from patient urine before its discharge into wastewater.

Evaluation of Novel 64Cu-Labeled Theranostic Gadolinium-Based Nanoprobes in HepG2 Tumor-Bearing Nude Mice

NASA Astrophysics Data System (ADS)

Hu, Pengcheng; Cheng, Dengfeng; Huang, Tao; Banizs, Anna B.; Xiao, Jie; Liu, Guobing; Chen, Quan; Wang, Yuenan; He, Jiang; Shi, Hongcheng

2017-09-01

Radiation therapy of liver cancer is limited by low tolerance of the liver to radiation. Radiosensitizers can effectively reduce the required radiation dose. AGuIX nanoparticles are small, multifunctional gadolinium-based nanoparticles that can carry radioisotopes or fluorescent markers for single-photon emission computed tomography (SPECT), positron emission tomography (PET), fluorescence imaging, and even multimodality imaging. In addition, due to the high atomic number of gadolinium, it can also serve as a tumor radiation sensitizer. It is critical to define the biodistribution and pharmacokinetics of these gadolinium-based nanoparticles to quantitate the magnitude and duration of their retention within the tumor microenvironment during radiotherapy. Therefore, in this study, we successfully labeled AGuIX with 64Cu through the convenient built-in chelator. The biodistribution studies indicated that the radiotracer 64Cu-AGuIX accumulates to high levels in the HepG2 xenograft of nude mice, suggesting that it would be a potential theranostic nanoprobe for image-guided radiotherapy in HCC. We also used a transmission electron microscope to confirm AGuIX uptake in the HepG2 cells. In radiation therapy studies, a decrease in 18F-FDG uptake was observed in the xenografts of the nude mice irradiated with AGuIX, which was injected 1 h before. These results provide proof-of-concept that AGuIX can be used as a theranostic radiosensitizer for PET imaging to guide radiotherapy for liver cancer.

Evaluation of Novel 64Cu-Labeled Theranostic Gadolinium-Based Nanoprobes in HepG2 Tumor-Bearing Nude Mice.

PubMed

Hu, Pengcheng; Cheng, Dengfeng; Huang, Tao; Banizs, Anna B; Xiao, Jie; Liu, Guobing; Chen, Quan; Wang, Yuenan; He, Jiang; Shi, Hongcheng

2017-09-06

Radiation therapy of liver cancer is limited by low tolerance of the liver to radiation. Radiosensitizers can effectively reduce the required radiation dose. AGuIX nanoparticles are small, multifunctional gadolinium-based nanoparticles that can carry radioisotopes or fluorescent markers for single-photon emission computed tomography (SPECT), positron emission tomography (PET), fluorescence imaging, and even multimodality imaging. In addition, due to the high atomic number of gadolinium, it can also serve as a tumor radiation sensitizer. It is critical to define the biodistribution and pharmacokinetics of these gadolinium-based nanoparticles to quantitate the magnitude and duration of their retention within the tumor microenvironment during radiotherapy. Therefore, in this study, we successfully labeled AGuIX with 64 Cu through the convenient built-in chelator. The biodistribution studies indicated that the radiotracer 64 Cu-AGuIX accumulates to high levels in the HepG2 xenograft of nude mice, suggesting that it would be a potential theranostic nanoprobe for image-guided radiotherapy in HCC. We also used a transmission electron microscope to confirm AGuIX uptake in the HepG2 cells. In radiation therapy studies, a decrease in 18 F-FDG uptake was observed in the xenografts of the nude mice irradiated with AGuIX, which was injected 1 h before. These results provide proof-of-concept that AGuIX can be used as a theranostic radiosensitizer for PET imaging to guide radiotherapy for liver cancer.

Relaxivity enhancement of aquated Tris(β-diketonate)gadolinium(III) chelates by confinement within ultrashort single-walled carbon nanotubes.

PubMed

Law, Justin J; Guven, Adem; Wilson, Lon J

2014-01-01

Ultrashort single-walled carbon nanotubes loaded with gadolinium ions (gadonanotubes) have been previously shown to exhibit extremely high T1 -weighted relaxivities (>100 mm(-1) s(-1) ). To further examine the effect of nanoconfinement on the relaxivity of gadolinium-based contrast agents for magnetic resonance imaging, a series of ultrashort single-walled carbon nanotube (US-tube) materials internally loaded with gadolinium chelates have been prepared and studied. US-tubes were loaded with Gd(acac)3  · 2H2 O, Gd(hfac)3  · 2H2 O, and Gd(thd)3 (acac = acetylacetone, hfac = hexafluoroacetylacetone, thd = tetramethylheptanedione). The longitudinal relaxivities of the prepared materials determined at 25°C in a 1.5 T field were 103 mm(-1) s(-1) for Gd(acac)3  · 2H2 O@US-tubes, 105 mm(-1) s(-1) for Gd(hfac)3  · 2H2 O@US-tubes and 26 mm(-1) s(-1) for Gd(thd)3 @US-tubes. Compared with the relaxivities obtained for the unloaded chelates (<10 mm(-1) s(-1) ) as well as accounting for the T1 reduction observed for the empty US-tubes, the boost in relaxivity for chelate-loaded US-tubes is attributed to confinement within the nanotube and depends on the number of coordinated water molecules. Copyright © 2014 John Wiley & Sons, Ltd.

Thermophysical Property Measurements of Liquid Gadolinium by Containerless Methods

NASA Astrophysics Data System (ADS)

Ishikawa, T.; Okada, J. T.; Paradis, P.-F.; Watanabe, Y.

2010-02-01

Thermophysical properties of liquid gadolinium were measured using non-contact diagnostic techniques with an electrostatic levitator. Over the 1585 K to 1920 K temperature range, the density can be expressed as ρ( T) = 7.41 × 103 - 0.46 ( T - T m) (kg · m-3) where T m = 1585 K, yielding a volume expansion coefficient of 6.2 × 10-5 K-1. In addition, the surface tension data can be fitted as γ( T) = 8.22 × 102 - 0.097( T - T m)(10-3 N · m-1) over the 1613 K to 1803 K span and the viscosity as η( T) = 1.7exp[1.4 × 104/( RT)](10-3 Pa · s) over the same temperature range.

Complex imaging features of accidental cerebral intraventricular gadolinium administration.

PubMed

Nayak, Nita B; Huang, Jimmy C; Hathout, Gasser M; Shaba, Wisam; El-Saden, Suzie M

2013-05-01

Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) is a contrast agent commonly used for enhancing MRI. In this paper, the authors report on 2 cases of postoperative inadvertent administration of Gd-DTPA directly into a ventriculostomy tubing side port that was mistaken for intravenous tubing. Both cases demonstrated a low signal on MRI throughout the ventricular system and dependent portions of the subarachnoid spaces, which was originally believed to be CSF with areas of T1 shortening in the nondependent portions of the subarachnoid spaces, and misinterpreted as basal leptomeningeal enhancement and meningitis. The authors propose that the appearance of profound T1 hypointensity within the ventricles and diffuse susceptibility artifact along the ependyma is pathognomonic of intraventricular Gd-DTPA and should be recognized.

High-mobility group box 1 inhibits HCO3− absorption in the medullary thick ascending limb through RAGE-Rho-ROCK-mediated inhibition of basolateral Na+/H+ exchange

PubMed Central

Watts, Bruns A.; George, Thampi; Badalamenti, Andrew

2016-01-01

High-mobility group box 1 (HMGB1) is a nuclear protein released extracellularly in response to infection or injury, where it activates immune responses and contributes to the pathogenesis of kidney dysfunction in sepsis and sterile inflammatory disorders. Recently, we demonstrated that HMGB1 inhibits HCO3− absorption in perfused rat medullary thick ascending limbs (MTAL) through a basolateral receptor for advanced glycation end products (RAGE)-dependent pathway that is additive to Toll-like receptor 4 (TLR4)-ERK-mediated inhibition by LPS (Good DW, George T, Watts BA III. Am J Physiol Renal Physiol 309: F720–F730, 2015). Here, we examined signaling and transport mechanisms that mediate inhibition by HMGB1. Inhibition of HCO3− absorption by HMGB1 was eliminated by the Rho-associated kinase (ROCK) inhibitor Y27632 and by a specific inhibitor of Rho, the major upstream activator of ROCK. HMGB1 increased RhoA and ROCK1 activity. HMGB1-induced ROCK1 activation was eliminated by the RAGE antagonist FPS-ZM1 and by inhibition of Rho. The Rho and ROCK inhibitors had no effect on inhibition of HCO3− absorption by bath LPS. Inhibition of HCO3− absorption by HMGB1 was eliminated by bath amiloride, 0 Na+ bath, and the F-actin stabilizer jasplakinolide, three conditions that selectively prevent inhibition of MTAL HCO3− absorption mediated through NHE1. HMGB1 decreased basolateral Na+/H+ exchange activity through activation of ROCK. We conclude that HMGB1 inhibits HCO3− absorption in the MTAL through a RAGE-RhoA-ROCK1 signaling pathway coupled to inhibition of NHE1. The HMGB1-RAGE-RhoA-ROCK1 pathway thus represents a potential target to attenuate MTAL dysfunction during sepsis and other inflammatory disorders. HMGB1 and LPS inhibit HCO3− absorption through different receptor signaling and transport mechanisms, which enables these pathogenic mediators to act directly and independently to impair MTAL function. PMID:27358052

Magnetic resonance imaging with gadolinium arthrography to assess acetabular cartilage delamination.

PubMed

Zaragoza, Edward; Lattanzio, Pierre-Jean; Beaule, Paul E

2009-01-01

Recent reports have demonstrated magnetic resonance imaging (MRI) as a promising technique in detecting articular cartilage lesions of the hip joint. The purpose of our study was to evaluate the diagnostic performance of MRI with gadolinium arthrography in detecting acetabular cartilage delamination in patients with pre-arthritic hip pain. 46 patients (48 hips) underwent surgical dislocation of the hip. Mean age was 38.8 (range 17-56). There were 26 males and 20 females. All patients had Magnetic Resonance Imaging with gadolinium arthrography (MRA) before undergoing open hip surgery where the acetabular cartilage was inspected. Acetabular cartilage delamination on MRA was seen on sagittal images as a linear intra-articular filling defect of low signal intensity >1mm in thickness on T1 weighted images and surrounded by contrast. On MRA all hips had a labral tear confirmed at surgery. At surgery 30 hips had evidence of acetabular cartilage delamination, 4 hips had ulceration and 14 had no articular cartilage damage. The majority of labral tears and cartilage damage were located in the antero-superior quadrant. The sensitivity and specificity of MRA detection of cartilage delamination confirmed at surgery were 97% and 84%, respectively. The positive and negative predictive values of the MRA finding were 90% and 94%, respectively. The presence of the acetabular cartilage delamination represents an early stage of articular cartilage degeneration. When evaluating a young adult with hip pain, labral tears in association with cartilage delamination should be considered. MRA represents an effective diagnostic tool.

Liver acquisition with acceleration volume acquisition gadolinium-enhanced magnetic resonance combined with T2 sequences in the diagnosis of local recurrence of rectal cancer.

PubMed

Cao, Wuteng; Li, Fangqian; Gong, Jiaying; Liu, Dechao; Deng, Yanhong; Kang, Liang; Zhou, Zhiyang

2016-11-22

To investigate the efficacy of liver acquisition with acceleration volume acquisition (LAVA) gadolinium-enhanced magnetic resonance (MR) sequences and to assess its added accuracy in diagnosing local recurrence (LR) of rectal cancer with conventional T2-weighted fast spin echo (FSE) sequences. Pelvic MRI, including T2-weighted FSE sequences, gadolinium-enhanced sequences of LAVA and T1-weighted FSE with fat suppression, was performed on 225 patients with postoperative rectal cancer. Two readers evaluated the presence of LR according to "T2" (T2 sequences only), "T2 + LAVA-Gad" (LAVA and T2 imaging), and "T2 + T1-fs-Gad" (T1 fat suppression-enhanced sequence with T2 images). To evaluate diagnostic efficiency, imaging quality with LAVA and T1-fs-Gad by subjective scores and the signal intensity (SI) ratio. In the result, the SI ratio of LAVA was significantly higher than that of T1-fs-Gad (p = 0.0001). The diagnostic efficiency of "T2 + LAVA-Gad" was better than that of "T2 + T1-fs-Gad" (p = 0.0016 for Reader 1, p = 0.0001 for Reader 2) and T2 imaging only (p = 0.0001 for Reader 1; p = 0.0001 for Reader 2). Therefore, LAVA gadolinium-enhanced MR increases the accuracy of diagnosis of LR from rectal cancer and could replace conventional T1 gadolinium-enhanced sequences in the postoperative pelvic follow-up of rectal cancer.

Gadolinium Enhanced MR Coronary Vessel Wall Imaging at 3.0 Tesla.

PubMed

Kelle, Sebastian; Schlendorf, Kelly; Hirsch, Glenn A; Gerstenblith, Gary; Fleck, Eckart; Weiss, Robert G; Stuber, Matthias

2010-10-11

Purpose. We evaluated the influence of the time between low-dose gadolinium (Gd) contrast administration and coronary vessel wall enhancement (LGE) detected by 3T magnetic resonance imaging (MRI) in healthy subjects and patients with coronary artery disease (CAD). Materials and Methods. Four healthy subjects (4 men, mean age 29 ± 3 years and eleven CAD patients (6 women, mean age 61 ± 10 years) were studied on a commercial 3.0 Tesla (T) whole-body MR imaging system (Achieva 3.0 T; Philips, Best, The Netherlands). T1-weighted inversion-recovery coronary magnetic resonance imaging (MRI) was repeated up to 75 minutes after administration of low-dose Gadolinium (Gd) (0.1 mmol/kg Gd-DTPA). Results. LGE was seen in none of the healthy subjects, however in all of the CAD patients. In CAD patients, fifty-six of 62 (90.3%) segments showed LGE of the coronary artery vessel wall at time-interval 1 after contrast. At time-interval 2, 34 of 42 (81.0%) and at time-interval 3, 29 of 39 evaluable segments (74.4%) were enhanced. Conclusion. In this work, we demonstrate LGE of the coronary artery vessel wall using 3.0 T MRI after a single, low-dose Gd contrast injection in CAD patients but not in healthy subjects. In the majority of the evaluated coronary segments in CAD patients, LGE of the coronary vessel wall was already detectable 30-45 minutes after administration of the contrast agent.

Bi-atrial fibrosis detected using three-dimensional late gadolinium enhancement magnetic resonance imaging in a patient with cardiac sarcoidosis.

PubMed

Spence, Stewart; Pena, Elena; Thornhill, Rebecca E; Nery, Pablo B; Birnie, David H

2018-05-01

Presented is the case of a 62-year old male with a history of sarcoidosis and sinus node dysfunction, who underwent late gadolinium enhancement magnetic resonance imaging, which demonstrated left ventricular hyperenhancement and bi-atrial fibrosis.

Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents

DOE PAGES

Rees, Julian A.; Deblonde, Gauthier J. -P.; An, Dahlia D.; ...

2018-03-13

Several MRI contrast agent clinical formulations are now known to leave deposits of the heavy metal gadolinium in the brain, bones, and other organs of patients. This persistent biological accumulation of gadolinium has been recently recognized as a deleterious outcome in patients administered Gd-based contrast agents (GBCAs) for MRI, prompting the European Medicines Agency to recommend discontinuing the use of over half of the GBCAs currently approved for clinical applications. Here, to address this problem, we find that the orally-available metal decorporation agent 3,4,3-LI(1,2-HOPO) demonstrates superior efficacy at chelating and removing Gd from the body compared to diethylenetriaminepentaacetic acid, amore » ligand commonly used in the United States in the GBCA Gadopentetate (Magnevist). Using the radiotracer 153Gd to obtain precise biodistribution data, the results herein, supported by speciation simulations, suggest that the prophylactic or post-hoc therapeutic use of 3,4,3-LI(1,2-HOPO) may provide a means to mitigate Gd retention in patients requiring contrast-enhanced MRI.« less

Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rees, Julian A.; Deblonde, Gauthier J. -P.; An, Dahlia D.

Several MRI contrast agent clinical formulations are now known to leave deposits of the heavy metal gadolinium in the brain, bones, and other organs of patients. This persistent biological accumulation of gadolinium has been recently recognized as a deleterious outcome in patients administered Gd-based contrast agents (GBCAs) for MRI, prompting the European Medicines Agency to recommend discontinuing the use of over half of the GBCAs currently approved for clinical applications. Here, to address this problem, we find that the orally-available metal decorporation agent 3,4,3-LI(1,2-HOPO) demonstrates superior efficacy at chelating and removing Gd from the body compared to diethylenetriaminepentaacetic acid, amore » ligand commonly used in the United States in the GBCA Gadopentetate (Magnevist). Using the radiotracer 153Gd to obtain precise biodistribution data, the results herein, supported by speciation simulations, suggest that the prophylactic or post-hoc therapeutic use of 3,4,3-LI(1,2-HOPO) may provide a means to mitigate Gd retention in patients requiring contrast-enhanced MRI.« less

[Combined use of contrast media containing iodine and gadolinium for imaging and intervention : A hitherto widely ignored topic in radiological practice].

PubMed

Golder, W

2012-02-01

The synchronous use of chemically different contrast media in the same body compartment is a challenge for the radiologist, whether it is scheduled or unexpected. However, to inject contrast media containing iodine and gadolinium at the same time can be a prerequisite for the examination of several organs or organ systems. Unlike other topics of contrast-enhanced imaging procedures, the difficulties encountered with double contrast injections have been widely ignored in the literature. In the absence of reliable data from experimental and clinical studies the radiologist is dependent on case reports, information provided by the contrast media manufacturers, personal communications, mostly scanty personal experiences and a skilful time management, in order to overcome the situation. Only the combination of X-ray, computed tomography and magnetic resonance arthrography can be performed without another thought. However, the more or less synchronous vascular application of contrast media containing iodine and gadolinium requires vigilance. The more seriously ill the patient is, the more caution is advised even if the decision on the combined administration has to be reached urgently. The following overview gives a description of the properties of contrast media containing iodine and gadolinium as far as interactions following simultaneous administration are concerned. Subsequently, the clinically relevant situations and constellations are outlined and analyzed.

Rapid colorimetric sensing of gadolinium by EGCG-derived AgNPs: the development of a nanohybrid bioimaging probe.

PubMed

Singh, Rohit Kumar; Mishra, Sourav; Jena, Satyapriya; Panigrahi, Bijayananda; Das, Bhaskar; Jayabalan, Rasu; Parhi, Pankaj Kumar; Mandal, Dindyal

2018-04-17

Polyphenol functionalized silver nanoparticles (AgNPs) have been developed and demonstrated as colorimetric sensors for the selective detection of gadolinium. The newly obtained AgNP-Gd3+ conjugates exhibit high aqueous dispersibility and excitation dependent fluorescence emission. The conjugates offer multicolor bioimaging potential owing to their excellent luminescence properties.

A first principles kinetic Monte Carlo investigation of the adsorption and mobility of gadolinium on the (100) surface of tungsten

NASA Astrophysics Data System (ADS)

Samin, Adib J.; Zhang, Jinsuo

2017-05-01

An accurate characterization of lanthanide adsorption and mobility on tungsten surfaces is important for pyroprocessing. In the present study, the adsorption and diffusion of gadolinium on the (100) surface of tungsten was investigated. It was found that the hollow sites were the most energetically favorable for the adsorption. It was further observed that a magnetic moment was induced following the adsorption of gadolinium on the tungsten surface and that the system with adsorbed hollow sites had the largest magnetization. A pathway for the surface diffusion of gadolinium was determined to occur by hopping between the nearest neighbor hollow sites via the bridge site and the activation energy for the hop was calculated to be 0.75 eV. The surface diffusion process was further assessed using two distinct kinetic Monte Carlo models; one that accounted for lateral adsorbate interactions up to the second nearest neighbor and one that did not account for such interatomic interactions in the adlayer. When the lateral interactions were included in the simulations, the diffusivity was observed to have a strong dependence on coverage (for the coverage values being studied). The effects of lateral interactions were further observed in a one-dimensional simulation of the diffusion equation where the asymmetry in the surface coverage profile upon its approach to a steady state distribution was clear in comparison with the simulations which did not account for those interactions.

Acrolein with an alpha, beta-unsaturated Carbonyl Group Inhibits LPS-induced Homodimerization of Toll-like Receptor 4

USDA-ARS?s Scientific Manuscript database

Acrolein is a highly electrophilic a,ß-unsaturated aldehyde present in a number of environmental sources, especially cigarette smoke. It reacts strongly with the thiol groups of cysteine residues by Michael addition and has been reported to inhibit nuclear factor-kB (NF-kB) activation by lipopolysac...

The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy

PubMed Central

Sancey, L; Kotb, S; Roux, S; Dufort, S; Bianchi, A; Crémillieux, Y; Fries, P; Coll, J-L; Rodriguez-Lafrasse, C; Janier, M; Dutreix, M; Barberi-Heyob, M; Boschetti, F; Denat, F; Louis, C; Porcel, E; Lacombe, S; Le Duc, G; Deutsch, E; Perfettini, J-L; Detappe, A; Verry, C; Berbeco, R; Butterworth, K T; McMahon, S J; Prise, K M; Perriat, P; Tillement, O

2014-01-01

A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed. PMID:24990037

Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue.

PubMed

Jost, Gregor; Frenzel, Thomas; Lohrke, Jessica; Lenhard, Diana Constanze; Naganawa, Shinji; Pietsch, Hubertus

2017-07-01

Signal hyperintensity on unenhanced MRI in certain brain regions has been reported after multiple administrations of some, but not all, gadolinium-based contrast agents (GBCAs). One potential initial pathway of GBCA entry into the brain, infiltration from blood into the cerebrospinal fluid (CSF), was systematically evaluated in this preclinical study. GBCA infiltration and distribution in the CSF were investigated in healthy rats using repeated fluid-attenuated MRI up to 4 h after high-dose (1.8 mmol/kg) administration of six marketed and one experimental GBCA. Additionally, gadolinium measurements in CSF, blood and brain tissue samples (after 24 h) were performed using inductively coupled plasma mass spectrometry. Enhanced MRI signals in the CSF spaces with similar distribution kinetics were observed for all GBCAs. No substantial differences in the gadolinium concentrations among the marketed GBCAs were found in the CSF, blood or brain tissue. After 4.5 h, the concentration in the CSF was clearly higher than in blood but was almost completely cleared and lower than the brain tissue concentration after 24 h. In contrast to the brain signal hyperintensities, no differences in penetration and distribution into the CSF of healthy rats exist among the marketed GBCAs. • Gadolinium-based contrast agents can cross the blood-CSF barrier. • Fluid-attenuated MRI shows GBCA distribution with CSF flow. • GBCA structure and physicochemical properties do not impact CSF penetration and distribution. • GBCA clearance from CSF was almost complete within 24 h in rats. • CSF is a potential pathway of GBCA entry into the brain.

Gadolinium embedded iron oxide nanoclusters as T1-T2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery

NASA Astrophysics Data System (ADS)

Wang, Xiaoyong; Zhou, Zijian; Wang, Zhiyong; Xue, Yunxin; Zeng, Yun; Gao, Jinhao; Zhu, Lei; Zhang, Xianzhong; Liu, Gang; Chen, Xiaoyuan

2013-08-01

This report illustrates a new strategy of designing a T1-T2 dual-modal magnetic resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into nanoclusters in the water phase with the help of stearic acid modified low molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO-stPEI nanoclusters possess good stability, monodispersity with narrow size distribution and competitive T1-T2 dual-modal MR imaging properties. The nanocomposite system is capable of binding and delivering siRNA for knockdown of a gene of interest while maintaining its magnetic properties and biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an important platform for safe and efficient gene delivery with non-invasive T1-T2 dual-modal MRI monitoring capability.This report illustrates a new strategy of designing a T1-T2 dual-modal magnetic resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into nanoclusters in the water phase with the help of stearic acid modified low molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO-stPEI nanoclusters possess good stability, monodispersity with narrow size distribution and competitive T1-T2 dual-modal MR imaging properties. The nanocomposite system is capable of binding and delivering siRNA for knockdown of a gene of interest while maintaining its magnetic properties and biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an important platform for safe and efficient gene delivery with non-invasive T1-T2 dual-modal MRI monitoring capability. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr02797j

The effect of boron and gadolinium burnable poisons on the hot-to-cold reactivity swing of a pressurized water reactor assembly

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galperin, A.; Segev, M.; Radkowsky, A.

1986-11-01

Control requirements for advanced pressurized water reactor designs must be met with heavy loadings of burnable poison rods, the required reactivity hold-down typically amounting to 30% or more in a poisoned subassembly. Two apparent choices for poisons are natural boron rods and natural gadolinium rods. Studied and analyzed is the effect of these two poisons on the hot-to-cold reactivity upswing. Compared with an upswing of 2.9% in a nonpoisoned assembly, the upswing in the gadolinium-poisoned assembly is 3.0%, and the upswing in the boron-poisoned assembly is 8.8%. Thus the hot-to-cold control penalty is almost nil for the choice of gadoliniummore » and is considerable for the choice of boron.« less

Usefulness of the advanced neuroimaging protocol based on plain and gadolinium-enhanced constructive interference in steady state images for gamma knife radiosurgery and planning microsurgical procedures for skull base tumors.

PubMed

Hayashi, Motohiro; Chernov, Mikhail F; Tamura, Noriko; Yomo, Shoji; Tamura, Manabu; Horiba, Ayako; Izawa, Masahiro; Muragaki, Yoshihiro; Iseki, Hiroshi; Okada, Yoshikazu; Ivanov, Pavel; Régis, Jean; Takakura, Kintomo

2013-01-01

Gamma Knife radiosurgery (GKS) is currently performed with 0.1 mm preciseness, which can be designated microradiosurgery. It requires advanced methods for visualizing the target, which can be effectively attained by a neuroimaging protocol based on plain and gadolinium-enhanced constructive interference in steady state (CISS) images. Since 2003, the following thin-sliced images are routinely obtained before GKS of skull base lesions in our practice: axial CISS, gadolinium-enhanced axial CISS, gadolinium-enhanced axial modified time-of-flight (TOF), and axial computed tomography (CT). Fusion of "bone window" CT and magnetic resonance imaging (MRI), and detailed three-dimensional (3D) delineation of the anatomical structures are performed with the Leksell GammaPlan (Elekta Instruments AB). Recently, a similar technique has been also applied to evaluate neuroanatomy before open microsurgical procedures. Plain CISS images permit clear visualization of the cranial nerves in the subarachnoid space. Gadolinium-enhanced CISS images make the tumor "lucid" but do not affect the signal intensity of the cranial nerves, so they can be clearly delineated in the vicinity to the lesion. Gadolinium-enhanced TOF images are useful for 3D evaluation of the interrelations between the neoplasm and adjacent vessels. Fusion of "bone window" CT and MRI scans permits simultaneous assessment of both soft tissue and bone structures and allows 3D estimation and correction of MRI distortion artifacts. Detailed understanding of the neuroanatomy based on application of the advanced neuroimaging protocol permits performance of highly conformal and selective radiosurgical treatment. It also allows precise planning of the microsurgical procedures for skull base tumors.

Investigation of Plutonium and Uranium Precipitation Behavior with Gadolinium as a Neutron Poison

DOE Office of Scientific and Technical Information (OSTI.GOV)

Visser, A.E.

2003-10-17

The caustic precipitation of plutonium (Pu)-containing solutions has been investigated to determine whether the presence of 3:1 uranium (U):Pu in solutions stored in the H-Canyon Facility at the U.S. Department of Energy's (DOE) Savannah River Site (SRS) would adversely impact the use of gadolinium nitrate (Gd(NO3)3) as a neutron poison. In the past, this disposition strategy has been successfully used to discard solutions containing approximately 100 kg of Pu to the SRS high level waste (HLW) system. In the current experiments, gadolinium (as Gd(NO3)3) was added to samples of a 3:1 U:Pu solution, a surrogate 3 g/L U solution, andmore » a surrogate 3 g/L U with 1 g/L Pu solution. A series of experiments was then performed to observe and characterize the precipitate at selected pH values. Solids formed at pH 4.5 and were found to contain at least 50 percent of the U and 94 percent of the Pu, but only 6 percent of the Gd. As the pH of the solution increased (e.g., pH greater than 14 with 1.2 or 3.6 M sodium hydroxide (NaOH) excess), the precipitate contained greater than 99 percent of the Pu, U, and Gd. After the pH greater than 14 systems were undisturbed for one week, no significant changes were found in the composition of the solid or supernate for each sample. The solids were characterized by X-ray diffraction (XRD) which found sodium diuranate (Na2U2O7) and gadolinium hydroxide (Gd(OH)3) at pH 14. Thermal gravimetric analysis (TGA) indicated sufficient water molecules were present in the solids to thermalize the neutrons, a requirement for the use of Gd as a neutron poison. Scanning electron microscopy (SEM) was also performed and the accompanying back-scattering electron analysis (BSE) found Pu, U, and Gd compounds in all pH greater than 14 precipitate samples. The rheological properties of the slurries at pH greater than 14 were also investigated by performing precipitate settling rate studies and measuring the viscosity and density of the materials. Based

Comparative theoretical study of the structures and stabilities of four typical gadolinium carboxylates in different scintillator solvents.

PubMed

Huang, Pin-Wen

2016-03-01

The structural properties and stabilities of four typical gadolinium carboxylates (Gd-CBX) in toluene, linear alkyl benzene (LAB), and phenyl xylyl ethane (PXE) solvents were theoretically studied using density functional theory (DFT/B3LYP with the basis sets 6-311G(d) and MWB54) and the polarizable continuum model (PCM). The average Gd-ligand interaction energies (E int, corrected for dispersion) and the values of the energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital (ΔHL) for the gadolinium complexes were calculated to compare the relative stabilities of the four Gd-CBX molecules in the three liquid scintillator solvents. According to the calculations, the values of E int and ΔHL for Gd-CBX in LAB are larger than the corresponding values in PXE and toluene. Gd-CBX may therefore be more compatible with LAB than with PXE and toluene. It was also found that, in the three scintillator solvents, the stabilities of the four Gd-CBX molecules increase in the order Gd-2EHA < Gd-2MVA < Gd-pivalate < Gd-TMHA.

Selective modification of NMR relaxation time in human colorectal carcinoma by using gadolinium-diethylenetriaminepentaacetic acid conjugated with monoclonal antibody 19-9.

PubMed Central

Curtet, C; Tellier, C; Bohy, J; Conti, M L; Saccavini, J C; Thedrez, P; Douillard, J Y; Chatal, J F; Koprowski, H

1986-01-01

Monoclonal antibody 19-9 (mAb 19-9) against human colon adenocarcinoma was conjugated with gadolinium X diethylenetriaminepentaacetic acid (Gd X DTPA) and used as a contrast agent in nuclear magnetic resonance (NMR) in an effort to improve tumor target selectivity in nude mice. The data indicate that Gd X DTPA-mAb 19-9 in solution decreased the T1 relaxation of water protons at 90 MHz in direct proportion to the gadolinium concentration, and this effect was greater than in Gd X DTPA solutions. T1 relaxation time at 90 MHz, measured in tumors removed from nude mice 24 hr after injection of Gd X DTPA-mAb 19-9 (Gd, 20 mumol/kg; 16 DTPA molecules per mAb molecule), was significantly decreased (by 15%) as compared with the control group. Similar results were obtained in tumors from mice injected with Gd X DTPA-mAb 19-9 solutions in which Gd was used at 2, 6, or 10 mumol/kg (16 DTPA molecules per mAb molecule). These doses are lower than those commonly used for Gd X DTPA (10-100 mumol/kg) as contrast agent. Tumor localization by the Gd X DTPA-mAb 19-9 complex containing radioactive Gd (0.3 microCi/microgram of 153Gd) to confirm scintigraphy revealed significant concentrations of the complex (5% of the injected dose per gram of tissue) in the tumor. Scan images recorded in planar scintigraphy at day 5 showed good visualization of tumors. Images PMID:3459174

Synthesis route and three different core-shell impacts on magnetic characterization of gadolinium oxide-based nanoparticles as new contrast agents for molecular magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Azizian, Gholamreza; Riyahi-Alam, Nader; Haghgoo, Soheila; Moghimi, Hamid Reza; Zohdiaghdam, Reza; Rafiei, Behrooz; Gorji, Ensieh

2012-10-01

Despite its good resolution, magnetic resonance imaging intrinsically has low sensitivity. Recently, contrast agent nanoparticles have been used as sensitivity and contrast enhancer. The aim of this study was to investigate a new controlled synthesis method for gadolinium oxide-based nanoparticle preparation. For this purpose, diethyleneglycol coating of gadolinium oxide (Gd2O3-DEG) was performed using new supervised polyol route, and small particulate gadolinium oxide (SPGO) PEGylation was obtained with methoxy-polyethylene-glycol-silane (550 and 2,000 Da) coatings as SPGO-mPEG-silane550 and 2,000, respectively. Physicochemical characterization and magnetic properties of these three contrast agents in comparison with conventional Gd-DTPA were verified by dynamic light scattering transmission electron microscopy, Fourier transform infrared spectroscopy, inductively coupled plasma, X-ray diffraction, vibrating sample magnetometer, and the signal intensity and relaxivity measurements were performed using 1.5-T MRI scanner. As a result, the nanoparticle sizes of Gd2O3-DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000 could be reached to 5.9, 51.3, 194.2 nm, respectively. The image signal intensity and longitudinal ( r 1) and transverse relaxivity ( r 2) measurements in different concentrations (0.3 to approximately 2.5 mM), revealed the r 2/ r 1 ratios of 1.13, 0.89, 33.34, and 33.72 for Gd-DTPA, Gd2O3-DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000, respectively. The achievement of new synthesis route of Gd2O3-DEG resulted in lower r 2/ r 1 ratio for Gd2O3-DEG than Gd-DTPA and other previous synthesized methods by this and other groups. The smaller r 2/ r 1 ratios of two PEGylated-SPGO contrast agents in our study in comparison with r 2/ r 1 ratio of previous PEGylation ( r 2/ r 1 = 81.9 for mPEG-silane 6,000 MW) showed that these new three introduced contrast agents could potentially be proper contrast enhancers for cellular and molecular MR imaging.

Microstructural Anisotropy of Magnetocaloric Gadolinium Cylinders: Effect on the Mechanical Properties of the Material

PubMed Central

Petrovič, Darja Steiner; Šturm, Roman; Naglič, Iztok; Markoli, Boštjan; Pepelnjak, Tomaž

2016-01-01

The development of advanced materials and technologies based on magnetocaloric Gd and its compounds requires an understanding of the dependency of mechanical properties on their underlying microstructure. Therefore, the aim of the study was to characterize microstructural inhomogeneities in the gadolinium that can be used in magnetocaloric refrigeration systems. Microstructures of magnetocaloric gadolinium cylinders were investigated by light microscopy and FE-SEM (Field Emission Scanning Electron Microscopy), EDS (Energy-dispersive X-ray Spectroscopy), and BSE (Back-scattered Electrons) in both the extrusion and the extrusion-transversal directions. XRD (X-ray Diffraction) analyses were performed to reveal the presence of calcium- and fluorine-based compounds. Metallographic characterization showed an oxidized and inhomogeneous microstructure of the cross-sections. The edges and the outer parts of the cylinders were oxidized more intensively on the surfaces directly exposed to the processing tools. Moreover, a significant morphological anisotropy of the non-metallic inclusions was observed. CaF inclusions act as active nucleation sites for internal oxidation. The non-metallic, Ca- and F-containing inclusions can be classified as complex calciumoxyfluorides. The solubility of Er and Yb in the CaF was negligible compared to the Gd matrix and/or the oxide phase. Lower mechanical properties of the material are a consequence of the lower structural integrity due to selective oxidation of surfaces and interfaces. PMID:28773502

Modulation of channel activity and gadolinium block of MscL by static magnetic fields.

PubMed

Petrov, Evgeny; Martinac, Boris

2007-02-01

The magnetic field of the Earth has for long been known to influence the behaviour and orientation of a variety of living organisms. Experimental studies of the magnetic sense have, however, been impaired by the lack of a plausible cellular and/or molecular mechanism providing meaningful explanation for detection of magnetic fields by these organisms. Recently, mechanosensitive (MS) ion channels have been implied to play a role in magnetoreception. In this study we have investigated the effect of static magnetic fields (SMFs) of moderate intensity on the activity and gadolinium block of MscL, the bacterial MS channel of large conductance, which has served as a model channel to study the basic physical principles of mechanosensory transduction in living cells. In addition to showing that direct application of the magnetic field decreased the activity of the MscL channel, our study demonstrates for the first time that SMFs can reverse the effect of gadolinium, a well-known blocker of MS channels. The results of our study are consistent with a notion that (1) the effects of SMFs on the MscL channels may result from changes in physical properties of the lipid bilayer due to diamagnetic anisotropy of phospholipid molecules and consequently (2) cooperative superdiamagnetism of phospholipid molecules under influence of SMFs could cause displacement of Gd(3+) ions from the membrane bilayer and thus remove the MscL channel block.

Gadolinium(III)-sensitized fluorescence of europium in its mixed-metal compounds with trifluroacetate

NASA Astrophysics Data System (ADS)

Kalinovskaya, I. V.; Zadorozhnaya, A. N.

2017-04-01

The fluorescence properties of mixed-metal compounds of Eu(III) and Gd(III) with trifluoroacetic acid, Eu1-хGdx(С2F3O2)3·yD·zH2O, where D - 1,10-phenanthroline, 2,2-dipyridil, diphenylguanidine, x = 0, 0.25, 0.5, or 0.7, were studied. Luminescence spectroscopic evidence and the examination of excitation spectra indicate the occurrence of efficient energy transfer from the gadolinium to the europium ion. The greatest promotion of Eu3+ photoluminescence at 615 nm is observed when Eu:Gd = 1:1.

Modification of the crystal structure of gadolinium gallium garnet by helium ion irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ostafiychuk, B. K.; Yaremiy, I. P., E-mail: yaremiy@rambler.ru; Yaremiy, S. I.

2013-12-15

The structure of gadolinium gallium garnet (GGG) single crystals before and after implantation by He{sup +} ions has been investigated using high-resolution X-ray diffraction methods and the generalized dynamic theory of X-ray scattering. The main types of growth defects in GGG single crystals and radiation-induced defects in the ion-implanted layer have been determined. It is established that the concentration of dislocation loops in the GGG surface layer modified by ion implantation increases and their radius decreases with an increase in the implantation dose.

Gadolinium for neutron detection in current nuclear instrumentation research: A review

NASA Astrophysics Data System (ADS)

Dumazert, J.; Coulon, R.; Lecomte, Q.; Bertrand, G. H. V.; Hamel, M.

2018-02-01

Natural gadolinium displays a number of remarkable physical properties: it is a rare earth element, composed of seven stable or quasi-stable isotopes, with an exceptionally high magnetization and a Curie point near room temperature. Its use in the field of nuclear instrumentation historically relates to its efficiency as a neutron poison in power reactors. Gadolinium is indeed the naturally occurring element with the highest interaction probability with neutrons at thermal energy, shared between Gd-157 (15.65%, 254000 b cross section) and Gd-155 (14.8%, 60900 b) isotopes. Considering that neutron capture results in an isotopic change, followed by a radiative rearrangement of nuclear and atomic structures, Gd may be embodied not merely as a neutron poison but as a neutron converter into a prompt photon and an electron source term. Depending on the nature and energy of the reaction products (from a few-keV Auger electrons up to 8 MeV gamma rays) that the detector aims at isolating as an indirect neutron signature, a variety of sensor media and counting methods have been introduced during the last decades. This review first draws a theoretical description of the radiative cascade following Gd(n , γ) capture. The cascade may be subdivided into regions of interest, each corresponding to dedicated detection designs and optimizations whose current status is detailed. This inventory has allowed the authors to extract and benchmark key figures of merit for the definition of a detection scheme: neutron attenuation, neutron sensitivity (cps/nv), gamma rejection, neutron detection limit in a mixed field, intrinsic or extrinsic moderation, and transportability. On this basis, the authors have identified promising paths for Gd-based neutron detection in contemporary instrumentation.

The use of innovative gadolinium-based contrast agent for MR-diagnosis of cancer in the experiment

NASA Astrophysics Data System (ADS)

Chernov, V.; Medvedeva, A.; Sinilkin, I.; Zelchan, R.; Grigorev, E.; Frolova, I.; Nam, I.

2016-02-01

The present study of the functional suitability and specific activity of the contrast agent gadolinium-based for magnetic resonance imaging demonstrated that the investigated contrast agent intensively accumulates in organs and anatomical structures of the experimental animals. In the model of tumor lesions in animals, study have shown that investigational contrast agent accumulates in the tumor tissue and retained there in for a long enough time.

Bicuculline and strychnine suppress the mesencephalic locomotor region-induced inhibition of group III muscle afferent input to the dorsal horn.

PubMed

Degtyarenko, A M; Kaufman, M P

2003-01-01

We examined the effect of iontophoretic application of bicuculline methiodide and strychnine hydrochloride on the mesencephalic locomotor region (MLR)-induced inhibition of dorsal horn cells in paralyzed cats. The activity of 60 dorsal horn cells was recorded extracellularly in laminae I, II, V-VII of spinal segments L7-S1. Each of the cells was shown to receive group III muscle afferent input as demonstrated by their responses to electrical stimulation of the tibial nerve (mean latency and threshold of activation: 20.1+/-6.4 ms and 15.2+/-1.4 times motor threshold, respectively). Electrical stimulation of the MLR suppressed transmission in group III muscle afferent pathways to dorsal horn cells. Specifically the average number of impulses generated by the dorsal horn neurons in response to a single pulse applied to the tibial nerve was decreased by 78+/-2.8% (n=60) during the MLR stimulation. Iontophoretic application (10-50 nA) of bicuculline and strychnine (5-10 mM) suppressed the MLR-induced inhibition of transmission of group III afferent input to laminae I and II cells by 69+/-5% (n=10) and 29+/-7% (n=7), respectively. Likewise, bicuculline and strychnine suppressed the MLR-induced inhibition of transmission of group III afferent input to lamina V cells by 59+/-13% (n=14) and 39+/-11% (n=10), respectively. Our findings raise the possibility that GABA and glycine release onto dorsal horn neurons in the spinal cord may play an important role in the suppression by central motor command of thin fiber muscle afferent-reflex pathways.

Geometry of electromechanically active structures in Gadolinium - doped Cerium oxides

DOE PAGES

Li, Yuanyuan; Kraynis, Olga; Kas, Joshua; ...

2016-05-20

Local distortions from average structure are important in many functional materials, such as electrostrictors or piezoelectrics, and contain clues about their mechanism of work. However, the geometric attributes of these distortions are exceedingly difficult to measure, leading to a gap in knowledge regarding their roles in electromechanical response. This task is particularly challenging in the case of recently reported non-classical electrostriction in Cerium-Gadolinium oxides (CGO), where only a small population of Ce-O bonds that are located near oxygen ion vacancies responds to external electric field. In this study, we used high-energy resolution fluorescence detection (HERFD) technique to collect X-ray absorptionmore » spectra in CGO in situ, with and without an external electric field, coupled with theoretical modeling to characterize three-dimensional geometry of electromechanically active units.« less

Geometry of electromechanically active structures in Gadolinium - doped Cerium oxides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yuanyuan; Zacharowicz, Renee; Frenkel, Anatoly I., E-mail: igor.lubomirsky@weizmann.ac.il, E-mail: anatoly.frenkel@yu.edu

2016-05-15

Local distortions from average structure are important in many functional materials, such as electrostrictors or piezoelectrics, and contain clues about their mechanism of work. However, the geometric attributes of these distortions are exceedingly difficult to measure, leading to a gap in knowledge regarding their roles in electromechanical response. This task is particularly challenging in the case of recently reported non-classical electrostriction in Cerium-Gadolinium oxides (CGO), where only a small population of Ce-O bonds that are located near oxygen ion vacancies responds to external electric field. We used high-energy resolution fluorescence detection (HERFD) technique to collect X-ray absorption spectra in CGOmore » in situ, with and without an external electric field, coupled with theoretical modeling to characterize three-dimensional geometry of electromechanically active units.« less

Adsorption Studies of Gadolinium ion on Graphitic Carbon Nitride

NASA Astrophysics Data System (ADS)

Kuila, S. K.; Kundu, T. K.

2018-03-01

Bulk graphitic carbon nitride (g-C3N4) is synthesized by thermal decomposition of urea and used as an adsorbent for gadolinium ion (Gd3+) from aqueous solution. Adsorption capacity of g-C3N4 is found to be influenced by initial Gd3+ concentration, solution pH and contact time. Adsorbed Gd3+is separated from g-C3N4 by ultracentrifuge. Initial and Gd ion accumulated g-C3N4 adsorbent are characterized by X-ray diffraction technique (XRD) for phase identification, UV-visible and Fourier transform infrared (FTIR) spectroscopy for adsorption characteristics and optical property, scanning electron microscopy (SEM) for morphological behaviour along with energy dispersive X-ray spectroscopy (EDS) for elemental study. HNO3(0.1M), NaOH (0.1M) and de-ionized water are used for desorption and around 97% quantitative recovery of Gd ion is observed.

Intraoperative Near-Infrared Optical Imaging Can Localize Gadolinium-Enhancing Gliomas During Surgery

PubMed Central

Lee, John Y-K.; Thawani, Jayesh P.; Pierce, John; Zeh, Ryan; Martinez-Lage, Maria; Chanin, Michelle; Venegas, Ollin; Nims, Sarah; Learned, Kim; Keating, Jane; Singhal, Sunil

2016-01-01

Background Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense. Objective To propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease. Methods Fifteen patients were identified and administered an FDA-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) prior to surgical resection. An NIR camera was utilized to localize the tumor prior to resection and to visualize surgical margins following resection. Neuropathology and MR imaging data were used to assess the accuracy and precision of NIR-fluorescence in identifying tumor tissue. Results NIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12/15 tumors were visualized with the NIR camera. The mean signal-to-background ratio was 9.5 ± 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with SBR (P = .03). Non-enhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71). Conclusion Using Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity. PMID:27741220

Reverse microemulsion synthesis of layered gadolinium hydroxide nanoparticles

NASA Astrophysics Data System (ADS)

Xu, Yadong; Suthar, Jugal; Egbu, Raphael; Weston, Andrew J.; Fogg, Andrew M.; Williams, Gareth R.

2018-02-01

A reverse microemulsion approach has been explored for the synthesis of layered gadolinium hydroxide (LGdH) nanoparticles in this work. This method uses oleylamine as a multifunctional agent, acting as surfactant, oil phase and base. 1-butanol is additionally used as a co-surfactant. A systematic study of the key reaction parameters was undertaken, including the volume ratio of surfactant (oleylamine) to water, the reaction time, synthesis temperature, and the amount of co-surfactant (1-butanol) added. It proved possible to obtain pristine LGdH materials at temperatures of 120 °C or below with an oleylamine: water ratio of 1:4. Using larger amounts of surfactant or higher temperatures caused the formation of Gd(OH)3, either as the sole product or as a major impurity phase. The LGdH particles produced have sizes of ca. 200 nm, with this size being largely independent of temperature or reaction time. Adjusting the amount of 1-butanol co-surfactant added permits the size to be varied between 200 and 300 nm.

Gadolinium-Based Contrast Agents for MR Cancer Imaging

PubMed Central

Zhou, Zhuxian; Lu, Zheng-Rong

2013-01-01

Magnetic resonance imaging (MRI) is a clinical imaging modality effective for anatomical and functional imaging of diseased soft tissues, including solid tumors. MRI contrast agents have been routinely used for detecting tumor at an early stage. Gadolinium based contrast agents are the most commonly used contrast agents in clinical MRI. There have been significant efforts to design and develop novel Gd(III) contrast agents with high relaxivity, low toxicity and specific tumor binding. The relaxivity of the Gd(III) contrast agents can be increased by proper chemical modification. The toxicity of Gd(III) contrast agents can be reduced by increasing the agents’ thermodynamic and kinetic stability, as well as optimizing their pharmacokinetic properties. The increasing knowledge in the field of cancer genomics and biology provides an opportunity for designing tumor-specific contrast agents. Various new Gd(III) chelates have been designed and evaluated in animal models for more effective cancer MRI. This review outlines the design and development, physicochemical properties, and in vivo properties of several classes of Gd(III)-based MR contrast agents for tumor imaging. PMID:23047730

Inhibition of Group IIA Secretory Phospholipase A2 and its Inflammatory Reactions in Mice by Ethanolic Extract of Andrographis paniculata, a Well-known Medicinal Food

PubMed Central

Kishore, V.; Yarla, N. S.; Zameer, F.; Nagendra Prasad, M. N.; Santosh, M. S.; More, S. S.; Rao, D. G.; Dhananjaya, Bhadrapura Lakkappa

2016-01-01

Andrographis paniculata Nees is an important medicinal plant found in the tropical regions of the world, which has been traditionally used in Indian and Chinese medicinal systems. It is also used as medicinal food. A. paniculata is found to exhibit anti-inflammatory activities; however, its inhibitory potential on inflammatory Group IIA phospholipases A2 (PLA2) and its associated inflammatory reactions are not clearly understood. The aim of the present study is to evaluate the inhibitory/neutralizing potential of ethanolic extract of A. paniculata on the isolated inflammatory PLA2 (VRV-PL-VIIIa) from Daboii rusellii pulchella (belonging to Group IIA inflammatory secretory PLA2 [sPLA2]) and its associated edema-induced activities in Swiss albino mice. A. paniculata extract dose dependently inhibited the Group IIA sPLA2 enzymatic activity with an IC50 value of 10.3 ± 0.5 μg/ml. Further, the extract dose dependently inhibited the edema formation, when co-injected with enzyme indicating that a strong correlation exists between lipolytic and pro-inflammatory activities of the enzyme. In conclusion, results of this study shows that the ethanolic extract of A. paniculata effectively inhibits Group IIA sPLA2 and its associated inflammatory activities, which substantiate its anti-inflammatory properties. The results of the present study warranted further studies to develop bioactive compound (s) in ethanolic extract of A. paniculata as potent therapeutic agent (s) for inflammatory diseases. SUMMARY This study emphasis the anti-inflammatory effect of A. paniculata by inhibiting the inflammatory Group IIA sPLA2 and its associated inflammatory activities such as edema. It was found that there is a strong correlation between lipolytic activity and pro-inflammatory activity inhibition. Therefore, the study suggests that the extract processes potent anti-inflammatory agents, which could be developed as a potential therapeutic agent against inflammatory and related diseases

Validation of the analytical methods in the LWR code BOXER for gadolinium-loaded fuel pins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paratte, J.M.; Arkuszewski, J.J.; Kamboj, B.K.

1990-01-01

Due to the very high absorption occurring in gadolinium-loaded fuel pins, calculations of lattices with such pins present are a demanding test of the analysis methods in light water reactor (LWR) cell and assembly codes. Considerable effort has, therefore, been devoted to the validation of code methods for gadolinia fuel. The goal of the work reported in this paper is to check the analysis methods in the LWR cell/assembly code BOXER and its associated cross-section processing code ETOBOX, by comparison of BOXER results with those from a very accurate Monte Carlo calculation for a gadolinium benchmark problem. Initial results ofmore » such a comparison have been previously reported. However, the Monte Carlo calculations, done with the MCNP code, were performed at Los Alamos National Laboratory using ENDF/B-V data, while the BOXER calculations were performed at the Paul Scherrer Institute using JEF-1 nuclear data. This difference in the basic nuclear data used for the two calculations, caused by the restricted nature of these evaluated data files, led to associated uncertainties in a comparison of the results for methods validation. In the joint investigations at the Georgia Institute of Technology and PSI, such uncertainty in this comparison was eliminated by using ENDF/B-V data for BOXER calculations at Georgia Tech.« less

Comparison of Helicobacter pylori Urease Inhibition by Rhizoma Coptidis, Cortex Phellodendri and Berberine: Mechanisms of Interaction with the Sulfhydryl Group.

PubMed

Li, Cailan; Xie, Jianhui; Chen, Xiaoying; Mo, Zhizhun; Wu, Wen; Liang, Yeer; Su, Zuqing; Li, Qian; Li, Yucui; Su, Ziren; Yang, Xiaobo

2016-03-01

Rhizoma Coptidis, Cortex Phellodendri, and berberine were reported to inhibit Helicobacter pylori. However, the underlying mechanism remained elusive. Urease plays a vital role in H. pylori colonization and virulence. In this work, aqueous extracts of Rhizoma Coptidis, Cortex Phellodendri of different origins, and purified berberine were investigated against H. pylori urease and jack bean urease to elucidate the inhibitory capacity, kinetics, and mechanism. Results showed that berberine was the major chemical component in Rhizoma Coptidis and Cortex Phellodendri, and the content of berberine in Rhizoma Coptidis was higher than in Cortex Phellodendri. The IC50 values of Rhizoma Coptidis were significantly lower than those Cortex Phellodendri and purified berberine, of which Coptis chinensis was shown to be the most active concentration- and time-dependent urease inhibitor. The Lineweaver-Burk plot analysis indicated that the inhibition pattern of C. chinensis against urease was noncompetitive for both H. pylori urease and jack bean urease. Thiol protectors (L-cysteine, glutathione, and dithiothreithol) significantly protected urease from the loss of enzymatic activity, while fluoride and boric acid showed weaker protection, indicating the active-site sulfhydryl group was possibly responsible for its inhibition. Furthermore, the urease inhibition proved to be reversible since C. chinensis-blocked urease could be reactivated by glutathione. The results suggested that the anti-urease activity of Rhizoma Coptidis was superior to that of Cortex Phellodendri and berberine, which was believed to be more likely to correlate to the content of total alkaloids rather than berberine monomer. The concentration- and time-dependent, reversible, and noncompetitive inhibition against urease by C. chinensis might be attributed to its interaction with the sulfhydryl group of the active site of urease. Georg Thieme Verlag KG Stuttgart · New York.

Global and Regional Brain Assessment with Quantitative MR Imaging in Patients with Prior Exposure to Linear Gadolinium-based Contrast Agents.

PubMed

Kuno, Hirofumi; Jara, Hernán; Buch, Karen; Qureshi, Muhammad Mustafa; Chapman, Margaret N; Sakai, Osamu

2017-04-01

Purpose To assess the association of global and regional brain relaxation times in patients with prior exposure to linear gadolinium-based contrast agents (GBCAs). Materials and Methods The institutional review board approved this cross-sectional study. Thirty-five patients (nine who had received GBCA gadopentetate dimeglumine injections previously [one to eight times] and 26 patients who did not) who underwent brain magnetic resonance (MR) imaging with a mixed fast spin-echo pulse sequence were assessed. The whole brain was segmented according to white and gray matter by using a dual-clustering algorithm. In addition, regions of interest were measured in the globus pallidus, dentate nucleus, thalamus, and pons. The Mann-Whitney U test was used to assess the difference between groups. Multiple regression analysis was performed to assess the association of T1 and T2 with prior GBCA exposure. Results T1 values of gray matter were significantly shorter for patients with than for patients without prior GBCA exposure (P = .022). T1 of the gray matter of the whole brain (P < .001), globus pallidus (P = .002), dentate nucleus (P = .046), and thalamus (P = .026) and T2 of the whole brain (P = .004), dentate nucleus (P = .023), and thalamus (P = .002) showed a significant correlation with the accumulated dose of previous GBCA administration. There was no significant correlation between T1 and the accumulated dose of previous GBCA injections in the white matter (P = .187). Conclusion Global and regional quantitative assessments of T1 and T2 demonstrated an association with prior GBCA exposure, especially for gray matter structures. The results of this study confirm previous research findings that there is gadolinium deposition in wider distribution throughout the brain. © RSNA, 2016 Online supplemental material is available for this article.

Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis.

PubMed

Fontana, Marianna; Pica, Silvia; Reant, Patricia; Abdel-Gadir, Amna; Treibel, Thomas A; Banypersad, Sanjay M; Maestrini, Viviana; Barcella, William; Rosmini, Stefania; Bulluck, Heerajnarain; Sayed, Rabya H; Patel, Ketna; Mamhood, Shameem; Bucciarelli-Ducci, Chiara; Whelan, Carol J; Herrey, Anna S; Lachmann, Helen J; Wechalekar, Ashutosh D; Manisty, Charlotte H; Schelbert, Eric B; Kellman, Peter; Gillmore, Julian D; Hawkins, Philip N; Moon, James C

2015-10-20

The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1-13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E', and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3-13.1; P<0.05). There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors. © 2015 The Authors.

Gadolinium-free MR in coarctation-can contrast-enhanced MR angiography be replaced?

PubMed

Kalmar, Peter I; Koestenberger, Martin; Marterer, Robert; Tschauner, Sebastian; Sorantin, Erich

2016-01-01

To determine the difference in vessel measurements, signal-to-noise ratio (SNR), and voxel size between contrast-enhanced and noncontrast magnetic resonance techniques in patients with coarctation of the aorta (CoA). In 39 patients, vessel size, SNR, and voxel size were compared in cine magnetic resonance imaging (MRI), gadolinium-free magnetic resonance angiography (Gd-free MRA), and contrast-enhanced MRA (ce-MRA). There was no significant difference in measurement and SNR, but there was a significant difference in voxel size (P<.001). Our results show that, in CoA patients, monitoring of vessel size using cine MRI and Gd-free MRA is equivalent to ce-MRA while being less invasive. Copyright © 2016 Elsevier Inc. All rights reserved.

Electronic transport in gadolinium atomic-size contacts

NASA Astrophysics Data System (ADS)

Olivera, B.; Salgado, C.; Lado, J. L.; Karimi, A.; Henkel, V.; Scheer, E.; Fernández-Rossier, J.; Palacios, J. J.; Untiedt, C.

2017-02-01

We report on the fabrication, transport measurements, and density functional theory (DFT) calculations of atomic-size contacts made of gadolinium (Gd). Gd is known to have local moments mainly associated with f electrons. These coexist with itinerant s and d bands that account for its metallic character. Here we explore whether and how the local moments influence electronic transport properties at the atomic scale. Using both scanning tunneling microscope and lithographic mechanically controllable break junction techniques under cryogenic conditions, we study the conductance of Gd when only few atoms form the junction between bulk electrodes made of the very same material. Thousands of measurements show that Gd has an average lowest conductance, attributed to single-atom contact, below 2/e2 h . Our DFT calculations for monostrand chains anticipate that the f bands are fully spin polarized and insulating and that the conduction may be dominated by s , p , and d bands. We also analyze the electronic transport for model nanocontacts using the nonequilibrium Green's function formalism in combination with DFT. We obtain an overall good agreement with the experimental results for zero bias and show that the contribution to the electronic transport from the f channels is negligible and that from the d channels is marginal.

Design and development of a Gadolinium-doped water Cherenkov detector

NASA Astrophysics Data System (ADS)

Poudyal, Nabin

This thesis describes a research and development project for neutron capture and detection in Gadolinium doped water. The Sanford Underground Research Facility (SURF) is exploring rare event physics, such as neutrinoless double beta decay (MAJORANA Project) and dark-matter detection (LUX experiment). The success of these experiments requires a careful study and understanding of background radiation, including flux and energy spectrum. The background radiation from surface contamination, radioactive decays of U-238, Th-232, Rn-222 in the surrounding rocks and muon induced neutrons have a large impact on the success of rare-event physics. The main objective of this R&D project is to measure the neutron flux contributing to ongoing experiments at SURF and suppress it by identification and capture method. For this purpose, we first modeled and designed a detector with Geant4 software. The approximate dimension of the detector is determined. The neutron capture percentage of the detector is estimated using Monte Carlo. The energy response of the detector is simulated. Next, we constructed the experimental detector, an acrylic rectangular tank (60cm x 30cm x 30cm), filled with Gadolinium-doped deionized water. The tank is coated with high efficient reflector and then taped with black electrical tape to make it opaque. The voltage dividers attached to PMTs are covered with mu-metal. Two 5-inch Hamamatsu Photomultiplier tubes were attached on both sides facing the tank to collect the Cherenkov light produced in the water. The detector utilizes the principle of Cherenkov light emission by a charged particle moving through a water at a speed higher than the speed of light in the water, hence it has an inherent energy threshold of Cherenkov photon production. This property reduces the lower energy backgrounds. Event data are obtained using the Data Acquisition hardware, Flash Analog to digital converter, along with Multi Instance Data Acquisition software. Post

Anomalous Hall effect in calcium-doped lanthanum cobaltite and gadolinium

NASA Astrophysics Data System (ADS)

Baily, Scott Alan

The physical origin of the anomalous (proportional to magnetization) Hall effect is not very well understood. While many theories account for a Hall effect proportional to the magnetization of a material, these theories often predict effects significantly smaller than those found in ferromagnetic materials. An even more significant deficiency of the conventional theories is that they predict an anomalous Hall resistivity that is proportional to a power of the resistivity, and in the absence of a metal insulator transition cannot account for the anomalous Hall effect that peaks near TC. Recent models based on a geometric, or Berry, phase have had a great deal of success describing the anomalous Hall effect in double-exchange systems (e.g., lanthanum manganite and chromium dioxide). In gadolinium, as in double-exchange magnets, the exchange interaction is mediated by the conduction electrons and the anomalous Hall effect may therefore resemble that of CrO2 and other metallic double-exchange ferromagnets. Lanthanum cobaltite is similar to manganite in many ways, but a strong double-exchange interaction is not present. Calcium-doped lanthanum cobaltite films were found to have the largest anomalous Hall effect of any ferromagnetic metal. The primary purpose of this study is to gain insight into the origin of the anomalous Hall effect with the hope that these theories can be extended to account for the effect in other materials. The Hall resistivity, magnetoresistance, and magnetization of a Gadolinium single crystal were measured in fields up to 30 T. Cobaltite films were grown via laser ablation and characterized by a variety of techniques. Hall resistivity, magnetoresistance, magnetization, and magnetothermopower of L 1-xCaxCoO3 samples with 0.15 < x < 0.4 were measured in fields up to 7 T. The Gd results suggest that Berry's phase contributes partially to the Hall effect near TC. Berry's phase theories hold promise for explaining the large anomalous Hall effect in

Synthesis and characterization of gadolinium nanosheets with bound rose bengal: potential use in photodynamic therapy and MRI

NASA Astrophysics Data System (ADS)

Stefanakis, Dimitrios; Seimenis, Ioannis; Ghanotakis, Demetrios

2014-11-01

Gadolinium (Gd) is a trivalent paramagnetic element, making it useful as a contrast agent for magnetic resonance imaging (MRI). Gd2(OH)5NO3· xH2O belongs to a new family of nanosheets. The advantages of these materials are their relatively small size, paramagnetic behavior, stability, lack of toxicity and highly ordered structure. In the present study, Gd2(OH)5NO3 nanosheets were functionalized with amino groups and modified with the photosensitiser rose bengal (RB). This surface modification makes possible the use of the nanosheets in photodynamic therapy. The coated nanosheets were characterized with X-ray diffraction, fourier transform infrared spectroscopy and UV-Vis spectroscopy, as well as transmission electron microscopy. The possibility of using these nanosheets as potential spin-lattice ( T 1) and spin-spin relaxation ( T 2) contrast agents in MRI was evaluated at 1.5 T. Finally, the ability of Gd2(OH)5NO3-RB to catalyze photooxidization reactions was examined using nuclear magnetic resonance (1H NMR) and gas chromatography-mass spectrometry (GC/MS).

Reciprocal inhibition in writer's cramp.

PubMed

Chen, R S; Tsai, C H; Lu, C S

1995-09-01

We studied the inhibition of median H-reflexes by conditioning stimuli on the radial nerve in 13 patients with writer's cramp, eight of the simple type and five of the dystonic type, and in 14 normal volunteers. The patients and controls were right-handed, and their right arms were studied. Asymptomatic left arms were also studied in nine of 13 patients. In the control group we identified three periods of inhibition, with maximum peaks at conditioning-test intervals of 0 ms (41 +/- 17%), 20 ms (40 +/- 13%), and 100 ms (36 +/- 20%). In the patient group, the amplitudes of inhibition of these three periods in both arms were significantly less than those in the control group. However, there were no significant differences in the amplitudes of inhibition of these three periods between symptomatic and asymptomatic arms. There were also no significant differences between simple and dystonic writer's cramps. Our results indicate that the attenuation of reciprocal inhibition was present not only in symptomatic arms but also in asymptomatic arms of patients with writer's cramp. The defect of reciprocal inhibition in the asymptomatic hand has never been documented. We suggest that the preexistent electrophysiological abnormality may provide an explanation for the development of hand cramp after shifted writing.

Gadolinium oxide nanoplates with high longitudinal relaxivity for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Cho, Minjung; Sethi, Richa; Ananta Narayanan, Jeyarama Subramanian; Lee, Seung Soo; Benoit, Denise N.; Taheri, Nasim; Decuzzi, Paolo; Colvin, Vicki L.

2014-10-01

Molecular-based contrast agents for magnetic resonance imaging (MRI) are often characterized by insufficient relaxivity, thus requiring the systemic injection of high doses to induce sufficient contrast enhancement at the target site. In this work, gadolinium oxide (Gd2O3) nanoplates are produced via a thermal decomposition method. The nanoplates have a core diameter varying from 2 to 22 nm, a thickness of 1 to 2 nm and are coated with either an oleic acid bilayer or an octylamine modified poly(acrylic acid) (PAA-OA) polymer layer. For the smaller nanoplates, longitudinal relaxivities (r1) of 7.96 and 47.2 (mM s)-1 were measured at 1.41 T for the oleic acid bilayer and PAA-OA coating, respectively. These values moderately reduce as the size of the Gd2O3 nanoplates increases, and are always larger for the PAA-OA coating. Cytotoxicity studies on human dermal fibroblast cells documented no significant toxicity, with 100% cell viability preserved up to 250 μM for the PAA-OA coated Gd2O3 nanoplates. Given the 10 times increase in longitudinal relaxivity over the commercially available Gd-based molecular agents and the favorable toxicity profile, the 2 nm PAA-OA coated Gd2O3 nanoplates could represent a new class of highly effective T1 MRI contrast agents.Molecular-based contrast agents for magnetic resonance imaging (MRI) are often characterized by insufficient relaxivity, thus requiring the systemic injection of high doses to induce sufficient contrast enhancement at the target site. In this work, gadolinium oxide (Gd2O3) nanoplates are produced via a thermal decomposition method. The nanoplates have a core diameter varying from 2 to 22 nm, a thickness of 1 to 2 nm and are coated with either an oleic acid bilayer or an octylamine modified poly(acrylic acid) (PAA-OA) polymer layer. For the smaller nanoplates, longitudinal relaxivities (r1) of 7.96 and 47.2 (mM s)-1 were measured at 1.41 T for the oleic acid bilayer and PAA-OA coating, respectively. These values

Investigation of terbium in the ferroelectric crystal, gadolinium molybdate, as a potential laser

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crouch, J.E.

A preliminary non-stimulated study of the laser host combination Gd(2 - x)Tb(x)(MoO4)3 is made. The host material, gadolinium molybdate (GMO), is a ferroelectric/ferroelastic crystal. An investigation of temperature and external electric field affects on the absorption and fluorescence of the crystal did not produce any unusual results. The terbium ion, Tb(3+), peak cross section in GMO for the 5D sub 4 to 7F sub 5 transition is 10 x 10 to the minus twenty first power sq. cm. at 300K. The wavelength of this four level laser transition is 543 nm. (GRA)

Europium-activated phosphors containing oxides of rare-earth and group-IIIB metals and method of making the same

DOEpatents

Comanzo, Holly Ann; Setlur, Anant Achyut; Srivastava, Alok Mani

2006-04-04

Europium-activated phosphors comprise oxides of at least a rare-earth metal selected from the group consisting of gadolinium, yttrium, lanthanum, and combinations thereof and at least a Group-IIIB metal selected from the group consisting of aluminum, gallium, indium, and combinations thereof. A method for making such phosphors comprises adding at least a halide of at least one of the selected Group-IIIB metals in a starting mixture. The method further comprises firing the starting mixture in an oxygen-containing atmosphere. The phosphors produced by such a method exhibit improved absorption in the UV wavelength range and improved quantum efficiency.

Europium-activated phosphors containing oxides of rare-earth and group-IIIB metals and method of making the same

DOEpatents

Comanzo, Holly Ann; Setlur, Anant Achyut; Srivastava, Alok Mani; Manivannan, Venkatesan

2004-07-13

Europium-activated phosphors comprise oxides of at least a rare-earth metal selected from the group consisting of gadolinium, yttrium, lanthanum, and combinations thereof and at least a Group-IIIB metal selected from the group consisting of aluminum, gallium, indium, and combinations thereof. A method for making such phosphors comprises adding at least a halide of at least one of the selected Group-IIIB metals in a starting mixture. The method further comprises firing the starting mixture in an oxygen-containing atmosphere. The phosphors produced by such a method exhibit improved absorption in the UV wavelength range and improved quantum efficiency.

Electronic structure, charge transfer, and intrinsic luminescence of gadolinium oxide nanoparticles: Experiment and theory

NASA Astrophysics Data System (ADS)

Zatsepin, D. A.; Boukhvalov, D. W.; Zatsepin, A. F.; Kuznetsova, Yu. A.; Mashkovtsev, M. A.; Rychkov, V. N.; Shur, V. Ya.; Esin, A. A.; Kurmaev, E. Z.

2018-04-01

The cubic (c) and monoclinic (m) polymorphs of Gd2O3 were studied using the combined analysis of several materials science techniques - X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and photoluminescence (PL) spectroscopy. Density functional theory (DFT) based calculations for the samples under study were performed as well. The cubic phase of gadolinium oxide (c-Gd2O3) synthesized using a precipitation method exhibits spheroidal-like nanoclusters with well-defined edges assembled from primary nanoparticles with an average size of 50 nm, whereas the monoclinic phase of gadolinium oxide (m-Gd2O3) deposited using explosive pyrolysis has a denser structure compared with natural gadolinia. This phase also has a structure composed of three-dimensional complex agglomerates without clear-edged boundaries that are ∼21 nm in size plus a cubic phase admixture of only 2 at.% composed of primary edge-boundary nanoparticles ∼15 nm in size. These atomic features appear in the electronic structure as different defects ([Gd…Osbnd OH] and [Gd…Osbnd O]) and have dissimilar contributions to the charge-transfer processes among the appropriate electronic states with ambiguous contributions in the Gd 5р - O 2s core-like levels in the valence band structures. The origin of [Gd…Osbnd OH] defects found by XPS was well-supported by PL analysis. The electronic and atomic structures of the synthesized gadolinias calculated using DFT were compared and discussed on the basis of the well-known joint OKT-van der Laan model, and good agreement was established.

Gadolinium-conjugated PLA-PEG nanoparticles as liver targeted molecular MRI contrast agent.

PubMed

Chen, Zhijin; Yu, Dexin; Liu, Chunxi; Yang, Xiaoyan; Zhang, Na; Ma, Chunhong; Song, Jibin; Lu, Zaijun

2011-09-01

A nanoparticle magnetic resonance imaging (MRI) contrast agent targeted to liver was developed by conjugation of gadolinium (Gd) chelate groups onto the biocompatible poly(l-lactide)-block-poly (ethylene glycol) (PLA-PEG) nanoparticles. PLA-PEG conjugated with diethylenetriaminopentaacetic acid (DTPA) was used to formulate PLA-PEG-DTPA nanoparticles by solvent diffusion method, and then Gd was loaded onto the nanoparticles by chelated with the unfolding DTPA on the surface of the PLA-PEG-DTPA nanoparticles. The mean size of the nanoparticles was 265.9 ± 6.7 nm. The relaxivity of the Gd-labeled nanoparticles was measured, and the distribution in vivo was evaluated in rats. Compared with conventional contrast agent (Magnevist), the Gd-labeled PLA-PEG nanoparticles showed significant enhancement both on liver targeting ability and imaging signal intensity. The T(1) and T(2) relaxivities per [Gd] of the Gd-labeled nanoparticles was 18.865 mM(-1) s(-1) and 24.863 mM(-1) s(-1) at 3 T, respectively. In addition, the signal intensity in vivo was stronger comparing with the Gd-DTPA and the T(1) weight time was lasting for 4.5 h. The liver targeting efficiency of the Gd-labeled PLA-PEG nanoparticles in rats was 14.57 comparing with Magnevist injection. Therefore, the Gd-labeled nanoparticles showed the potential as targeting molecular MRI contrast agent for further clinical utilization.

Magnetic and magnetothermal studies of pure and doped gadolinium silicide nanoparticles for self-controlled hyperthermia applications

NASA Astrophysics Data System (ADS)

Alnasir, M. Hisham; Awan, M. S.; Manzoor, Sadia

2018-03-01

We report on magnetic and magnetothermal properties of undoped and doped gadolinium silicide (Gd5Si4) nanoparticles with the objective of simultaneously attaining high specific absorption rate (SAR) and low Curie temperature (TC) suitable for self-controlled hyperthermia applications for which TC ∼ 315-320 K. Pellets of doped gadolinium silicide Gd5(Si1-xGex)4 and (Gd1-xRx)5Si4 with R = Ho, Nd and Er and 0 ≤ x ≤ 0.35 were made by arc melting and reduced to nanoparticulate form by surfactant assisted ball milling. Structural and morphological studies were done using X-ray diffraction and scanning electron microscopy respectively. All samples show soft magnetic properties. At low fields there is a ferromagnetic to paramagnetic transition that reduces remanance and coercivity to zero making these materials very attractive for biomedical applications. Zero-field-cooled thermal demagnetization measurements showed that TC of these nanoparticles can be lowered to lie within the limits required for self-controlled hyperthermia by varying the dopant concentration. Specific absorption rates (SAR's) were obtained from magnetothermia measurements made in an ac magnetic field of amplitude 10 Oe and frequency 300 kHz. We have identified samples that have SAR values larger or comparable to those of magnetite and several ferrite nanoparticles, while having Curie temperatures that are low enough for self controlled hyperthermia applications.

Active extravasation of gadolinium-based contrast agent into the subdural space following lumbar puncture.

PubMed

Kothari, Pranay D; Hanser, Evelyn M; Wang, Harrison; Farid, Nikdokht

2016-01-01

A 38year-old male presented with cauda equina syndrome following multiple lumbar puncture attempts. Lumbar spine magnetic resonance imaging (MRI) showed a subdural hematoma and an area of apparent contrast enhancement in the spinal canal on sagittal post-contrast images. Axial post-contrast images obtained seven minutes later demonstrated an increase in size and change in shape of the region of apparent contrast enhancement, indicating active extravasation of the contrast agent. This is the first reported case of active extravasation of gadolinium-based contrast agent in the spine. Copyright © 2016 Elsevier Inc. All rights reserved.

Retention of gadolinium compounds used in magnetic resonance imaging: a critical review and the recommendations of regulatory agencies.

PubMed

Martí-Bonmatí, L; Martí-Bonmatí, E

The Spanish Agency for Drugs and Healthcare Products (AEMPS), based on the recommendations of the European Committee for Risk Assessment in Pharmacovigilance, established on 13 March 2017 that linear gadolinium-based MR contrast media, such as MultiHance, Omniscan, Magnevist (currently not marketed) and Optimark (no longer marketed in Spain), the clinical benefits do not outweigh the potential risks derived from their use. AEMPS recommends to suspend its marketing for general use based on the retention of these compounds in the brain. On the other hand, the AEMPS justifies the maintenance of Primovist and MultiHance for liver studies, and Magnevist of intra-articular administration (not commercialized in Spain), and justified the almost exclusive use of macrocyclic structure contrasts (Gadovist, ProHance and Dotarem). However, this retention is known to be different for each of the contrast media. All existing gadolinium contrasts agents have a distribution phase with tissue retention, due to a very slow exchange, in the interstitium of bone, skin, kidney, brain and other organs. The existence of histological effects or clinical symptoms associated with the accumulation of these trace amounts of gadolinium has not been demonstrated. The major toxicological concern with these contrast agents is related to nephrogenic systemic fibrosis (NSF). Since the safety profiles are mainly related to the interstitial retention space in the tissues, it does not seem justified to actually exclude contrast media that do not have cases related to the NSF. Based on all of this, we disagree with the latest AEMPS recommendation suggesting the marketing stoppage of linear agents without considering the individual retention profiles. This recommendation is not based neither on the data nor existing knowledge about the retention, relaxivity and clinical efficiency of the Gd compounds. It is therefore necessary to carry out prospective studies on the histological and clinical relevance of

Metastatic group 3 medulloblastoma is driven by PRUNE1 targeting NME1-TGF-β-OTX2-SNAIL via PTEN inhibition.

PubMed

Ferrucci, Veronica; de Antonellis, Pasqualino; Pennino, Francesco Paolo; Asadzadeh, Fatemeh; Virgilio, Antonella; Montanaro, Donatella; Galeone, Aldo; Boffa, Iolanda; Pisano, Ida; Scognamiglio, Iolanda; Navas, Luigi; Diana, Donatella; Pedone, Emilia; Gargiulo, Sara; Gramanzini, Matteo; Brunetti, Arturo; Danielson, Laura; Carotenuto, Marianeve; Liguori, Lucia; Verrico, Antonio; Quaglietta, Lucia; Errico, Maria Elena; Del Monaco, Valentina; D'Argenio, Valeria; Tirone, Felice; Mastronuzzi, Angela; Donofrio, Vittoria; Giangaspero, Felice; Picard, Daniel; Remke, Marc; Garzia, Livia; Daniels, Craig; Delattre, Olivier; Swartling, Fredrik J; Weiss, William A; Salvatore, Francesco; Fattorusso, Roberto; Chesler, Louis; Taylor, Michael D; Cinalli, Giuseppe; Zollo, Massimo

2018-05-01

Genetic modifications during development of paediatric groups 3 and 4 medulloblastoma are responsible for their highly metastatic properties and poor patient survival rates. PRUNE1 is highly expressed in metastatic medulloblastoma group 3, which is characterized by TGF-β signalling activation, c-MYC amplification, and OTX2 expression. We describe the process of activation of the PRUNE1 signalling pathway that includes its binding to NME1, TGF-β activation, OTX2 upregulation, SNAIL (SNAI1) upregulation, and PTEN inhibition. The newly identified small molecule pyrimido-pyrimidine derivative AA7.1 enhances PRUNE1 degradation, inhibits this activation network, and augments PTEN expression. Both AA7.1 and a competitive permeable peptide that impairs PRUNE1/NME1 complex formation, impair tumour growth and metastatic dissemination in orthotopic xenograft models with a metastatic medulloblastoma group 3 cell line (D425-Med cells). Using whole exome sequencing technology in metastatic medulloblastoma primary tumour cells, we also define 23 common 'non-synonymous homozygous' deleterious gene variants as part of the protein molecular network of relevance for metastatic processes. This PRUNE1/TGF-β/OTX2/PTEN axis, together with the medulloblastoma-driver mutations, is of relevance for future rational and targeted therapies for metastatic medulloblastoma group 3.10.1093/brain/awy039_video1awy039media15742053534001.

Gadolinium-loaded gel scintillators for neutron and antineutrino detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riddle, Catherine Lynn; Akers, Douglas William; Demmer, Ricky Lynn

A gadolinium (Gd) loaded scintillation gel (Gd-ScintGel) compound allows for neutron and gamma-ray detection. The unique gel scintillator encompasses some of the best features of both liquid and solid scintillators, yet without many of the disadvantages associated therewith. Preferably, the gel scintillator is a water soluble Gd-DTPA compound and water soluble fluorophores such as: CdSe/ZnS (or ZnS) quantum dot (Q-dot) nanoparticles, coumarin derivatives 7-hydroxy-4-methylcoumarin, 7-hydroxy-4-methylcoumarin-3-acetic acid, 7-hydroxycoumarin-3-carboxylic acid, and Alexa Fluor 350 as well as a carbostyril compound, carbostyril 124 in a stable water-based gel, such as methylcellulose or polyacrylamide polymers. The Gd-loaded ScintGel allows for a homogenious distribution ofmore » the Gd-DTPA and the fluorophores, and yields clean fluorescent emission peaks. A moderator, such as deuterium or a water-based clear polymer, can be incorporated in the Gd-ScintGel. The gel scintillators can be used in compact detectors, including neutron and antineutrino detectors.« less

Luminescence properties and electronic structure of Ce{sup 3+}-doped gadolinium aluminum garnet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dotsenko, V.P., E-mail: ssclab@ukr.net; Berezovskaya, I.V.; Voloshinovskii, A.S.

2015-04-15

Highlights: • The luminescence properties of Ce{sup 3+} ions in (Y, Gd){sub 3}Al{sub 5}O{sub 12} are analyzed. • The Gd{sup 3+} → Y{sup 3+} substitution leads to increasing of Ce{sup 3+} noncubic crystal field splitting parameter. • The excitation spectra for the Ce{sup 3+} emission in GdAG contain bands at 6.67, 7.75, and 9.76 eV. • These features are due to the Ce{sup 3+}-bound exciton formation and O 2p → Al 3s, 3p transitions. • Contributions from Al atoms to the conduction-band density of states are quite essential. - Abstract: Yttrium-gadolinium aluminum garnets (YGdAG) doped with Ce{sup 3+} ions havemore » been prepared by co-precipitation method. The luminescent properties of Ce{sup 3+} ions in Gd{sub 3(1−x)}Ce{sub 3x}Al{sub 5}O{sub 12} (x = 0.01) have been studied upon excitation in the 2–20 eV region. The substitution of Gd{sup 3+} for Y{sup 3+} in the garnet structure results in broadening the emission band and shifting its maximum towards the longer wavelengths. It was found that in addition to the 4f → 5d excitation bands of Ce{sup 3+} ions, the excitation spectra for the Ce{sup 3+} emission contain bands at 6.67, 7.75, and 9.76 eV. These bands are attributed to the Ce{sup 3+}-bound exciton formation and O 2p → Al 3s, 3p transitions, respectively. Although gadolinium states dominate near the bottom of the conduction band of Gd{sub 3}Al{sub 5}O{sub 12}, contributions from Al{sub tetr} and Al{sub oct} atoms to the conduction-band density of states are evaluated as quite essential.« less

Comparison of nephrotoxicity between two gadolinium-contrasts, gadodiamide and gadopentetate in patients with mildly diminished renal failure.

PubMed

Naito, Shokichi; Tazaki, Hiromi; Okamoto, Tomoko; Takeuchi, Kazuhiro; Kan, Shinichi; Takeuchi, Yasuo; Kamata, Kouju

2017-01-01

Although gadolinium (Gd)-based contrast media have been found to be nephrotoxic, their nephrotoxicity, and the dependence of nephrotoxicity on chelate types, have not been assessed in patients with normal or mildly diminished renal failure. This prospective, randomized study compared the nephrotoxicity of low doses of the nonionic Gd-based contrast medium gadodiamide (Omniscan®) and the ionic Gd-based contrast medium gadopentetate (Magnevist®) in patients with serum creatinine < 1.6 mg/dL. Patients aged 20 to 80 years, weighing 45 to 70 kg and with normal or < 1.6 mg/dL Serum-creatinine in the 3 months prior to undergoing magnetic resonance imaging (MRI) of brain, were enrolled. Patients were randomized to receive 0.1 mol/kg gadodiamide or gadopentetate. Serum-creatinine, serum cystatin-C, estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula, and estimated creatinine clearance rate (eCCr) using the Cockcroft-Gault formula were measured just before and 16-80 hr after MRI. Groups were compared statistically by Mann-Whitney U-tests and Wilcoxon signed-rank tests. There were no significant differences in clinical characteristics between the gadodiamide (n = 43) and gadopentetate (n = 59) groups. Serum-creatinine, eGFR and eCCr before and 16-80 hr after MRI did not differ significantly within either group or between the two groups. Serum cystatin-C was significantly higher 16-80 hr after than before MRI only in the gadodiamide group (0.79 ± 0.21 vs. 0.74 ± 0.14 mg/L, p = 0.028). The ionic contrast medium, gadopentetate, did not affect renal function during MRI, whereas the nonionic contrast medium, gadodiamide, affected renal function transiently.

Cross-resistance to herbicides of five ALS-inhibiting groups and sequencing of the ALS gene in Cyperus difformis L.

PubMed

Merotto, Aldo; Jasieniuk, Marie; Osuna, Maria D; Vidotto, Francesco; Ferrero, Aldo; Fischer, Albert J

2009-02-25

Resistance to ALS-inhibiting herbicides in Cyperus difformis has evolved rapidly in many rice areas worldwide. This study identified the mechanism of resistance, assessed cross-resistance patterns to all five chemical groups of ALS-inhibiting herbicides in four C. difformis biotypes, and attempted to sequence the ALS gene. Whole-plant and ALS enzyme activity dose-response assays indicated that the WA biotype was resistant to all ALS-inhibiting herbicides evaluated. The IR biotype was resistant to bensulfuron-methyl, orthosulfamuron, imazethapyr, and propoxycarbazone-sodium and less resistant to bispyribac-sodium and halosulfuron-methyl, and susceptible to penoxsulam. ALS enzyme activity assays indicated that resistance is due to an altered target site yet mutations previously found to endow target-site resistance in weeds were not detected in the sequences obtained. The inability to detect resistance mutations in C. difformis may result from the presence of additional ALS genes, which were not amplified by the primers used. This study reports the first ALS gene sequence from Cyperus difformis. Certain ALS-inhibiting herbicides can still be used to control some resistant C. difformis biotypes. However, because cross-resistance to all five classes of ALS-inhibitors was detected in other resistant biotypes, these herbicides should only be used within an integrated weed management program designed to delay the evolution of herbicide resistance.

Quantification and Assessment of the Chemical Form of Residual Gadolinium in the Brain After Repeated Administration of Gadolinium-Based Contrast Agents

PubMed Central

Frenzel, Thomas; Apte, Chirag; Jost, Gregor; Schöckel, Laura; Lohrke, Jessica; Pietsch, Hubertus

2017-01-01

Objective Multiple clinical and preclinical studies have reported a signal intensity increase and the presence of gadolinium (Gd) in the brain after repeated administration of Gd-based contrast agents (GBCAs). This bioanalytical study in rat brain tissue was initiated to investigate whether the residual Gd is present as intact GBCA or in other chemical forms by using tissue fractionation and chromatography. Materials and Methods Rats were divided randomly in 6 groups of 10 animals each. They received 10 daily injections of 2.5 mmol/kg bodyweight of 1 of 5 different GBCAs: linear GBCAs such as gadodiamide (Omniscan; GE Healthcare), gadopentetate dimeglumine (Gd-DTPA, Magnevist; Bayer), or gadobenate dimeglumine (Multihance; Bracco) and macrocyclic GBCAs such as gadobutrol (Gadovist; Bayer) and gadoterate meglumine (Gd-DOTA, Dotarem; Guerbet) or saline. On days 3 and 24 after the last injection (p.i.), 5 randomly chosen animals of each group were killed by exsanguination, and their brains were excised and divided into cerebrum, pons, and cerebellum. The brain sections were homogenized by sonication in ice-cold buffer at pH 7.4. Soluble and insoluble fractions were separated by centrifugation, and the soluble fractions were further separated by gel permeation chromatography (GPC). The Gd concentration in all tissue fractions and in the GPC eluate was measured by inductively coupled plasma–mass spectrometry. In a recovery control experiment, all GBCAs were spiked to blank brain tissue and more than 94% recovery of Gd in the tissue fractions was demonstrated. Results Only traces of the administered Gd were found in the rat brain tissue on day 3 and day 24 p.i. In the animals treated with macrocyclic GBCAs, Gd was found only in the soluble brain fraction and was present solely as low molecular weight molecules, most likely the intact GBCA. In the animals treated with linear GBCAs Gd was found to a large extent in the insoluble tissue fraction. The Gd concentration in

Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis

PubMed Central

Fontana, Marianna; Pica, Silvia; Reant, Patricia; Abdel-Gadir, Amna; Treibel, Thomas A.; Banypersad, Sanjay M.; Maestrini, Viviana; Barcella, William; Rosmini, Stefania; Bulluck, Heerajnarain; Sayed, Rabya H.; Patel, Ketna; Mamhood, Shameem; Bucciarelli-Ducci, Chiara; Whelan, Carol J.; Herrey, Anna S.; Lachmann, Helen J.; Wechalekar, Ashutosh D.; Manisty, Charlotte H.; Schelbert, Eric B.; Kellman, Peter; Gillmore, Julian D.; Hawkins, Philip N.

2015-01-01

Background— The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. Methods and Results— Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1–13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E′, and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3–13.1; P<0.05). Conclusions— There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after

Group III metabotropic glutamate receptors inhibit hyperalgesia in animal models of inflammation and neuropathic pain.

PubMed

Goudet, Cyril; Chapuy, Eric; Alloui, Abdelkrim; Acher, Francine; Pin, Jean-Philippe; Eschalier, Alain

2008-07-01

Glutamate plays a key role in modulation of nociceptive processing. This excitatory amino acid exerts its action through two distinct types of receptors, ionotropic and metabotropic glutamate receptors (mGluRs). Eight mGluRs have been identified and divided in three groups based on their sequence similarity, pharmacology and G-protein coupling. While the role of group I and II mGluRs is now well established, little is known about the part played by group III mGluRs in pain. In this work, we studied comparatively the involvement of spinal group III mGluR in modulation of acute, inflammatory and neuropathic pain. While intrathecal injection of ACPT-I, a selective group III mGluR agonist, failed to induce any change in vocalization thresholds of healthy animals submitted to mechanical or thermal stimuli, it dose-dependently inhibited the nociceptive behavior of rats submitted to the formalin test and the mechanical hyperalgesia associated with different animal models of inflammatory (carrageenan-treated and monoarthritic rats) or neuropathic pain (mononeuropathic and vincristine-treated rats). Similar effects were also observed following intrathecal injection of PHCCC, a positive allosteric modulator of mGlu4. Antihyperalgesia induced by ACPT-I was blocked either by LY341495, a nonselective antagonist of mGluR, by MAP4, a selective group III antagonist. This study provide new evidences supporting the role of spinal group III mGluRs in the modulation of pain perception in different pathological pain states of various etiologies but not in normal conditions. It more particularly highlights the specific involvement of mGlu4 in this process and may be a useful therapeutic approach to chronic pain treatment.

Role of late gadolinium enhancement cardiovascular magnetic resonance in the risk stratification of hypertrophic cardiomyopathy.

PubMed

Ismail, Tevfik F; Jabbour, Andrew; Gulati, Ankur; Mallorie, Amy; Raza, Sadaf; Cowling, Thomas E; Das, Bibek; Khwaja, Jahanzaib; Alpendurada, Francisco D; Wage, Ricardo; Roughton, Michael; McKenna, William J; Moon, James C; Varnava, Amanda; Shakespeare, Carl; Cowie, Martin R; Cook, Stuart A; Elliott, Perry; O'Hanlon, Rory; Pennell, Dudley J; Prasad, Sanjay K

2014-12-01

Myocardial fibrosis identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in patients with hypertrophic cardiomyopathy (HCM) is associated with adverse cardiovascular events, but its value as an independent risk factor for sudden cardiac death (SCD) is unknown. We investigated the role of LGE-CMR in the risk stratification of HCM. We conducted a prospective cohort study in a tertiary referral centre. Consecutive patients with HCM (n=711, median age 56.3 years, IQR 46.7-66.6; 70.0% male) underwent LGE-CMR and were followed for a median 3.5 years. The primary end point was SCD or aborted SCD. Overall, 471 patients (66.2%) had myocardial fibrosis (median 5.9% of left ventricular mass, IQR: 2.2-13.3). Twenty-two (3.1%) reached the primary end point. The extent but not the presence of fibrosis was a significant univariable predictor of the primary end point (HR per 5% LGE: 1.24, 95% CI 1.06 to 1.45; p=0.007 and HR for LGE: 2.69, 95% CI 0.91 to 7.97; p=0.073, respectively). However, on multivariable analysis, only LV-EF remained statistically significant (HR: 0.92, 95% CI 0.89 to 0.95; p<0.001). For the secondary outcome of cardiovascular mortality/aborted SCD, the presence and the amount of fibrosis were significant predictors on univariable but not multivariable analysis after adjusting for LV-EF and non-sustained ventricular tachycardia. The amount of myocardial fibrosis was a strong univariable predictor of SCD risk. However, this effect was not maintained after adjusting for LV-EF. Further work is required to elucidate the interrelationship between fibrosis and traditional predictors of outcome in HCM. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Heterogeneous intratumoral distribution of gadolinium nanoparticles within U87 human glioblastoma xenografts unveiled by micro-PIXE imaging.

PubMed

Carmona, Asuncion; Roudeau, Stéphane; L'Homel, Baptiste; Pouzoulet, Frédéric; Bonnet-Boissinot, Sarah; Prezado, Yolanda; Ortega, Richard

2017-04-15

Metallic nanoparticles have great potential in cancer radiotherapy as theranostic drugs since, they serve simultaneously as contrast agents for medical imaging and as radio-therapy sensitizers. As with other anticancer drugs, intratumoral diffusion is one of the main limiting factors for therapeutic efficiency. To date, a few reports have investigated the intratumoral distribution of metallic nanoparticles. The aim of this study was to determine the quantitative distribution of gadolinium (Gd) nanoparticles after direct intratumoral injection within U87 human glioblastoma tumors grafted in mice, using micro-PIXE (Particle Induced X-ray Emission) imaging. AGuIX (Activation and Guiding of Irradiation by X-ray) 3 nm particles composed of a polysiloxane network surrounded by gadolinium chelates were used. PIXE results indicate that the direct injection of Gd nanoparticles in tumors results in their heterogeneous diffusion, probably related to variations in tumor density. All tumor regions contain Gd, but with markedly different concentrations, with a more than 250-fold difference. Also Gd can diffuse to the healthy adjacent tissue. This study highlights the usefulness of mapping the distribution of metallic nanoparticles at the intratumoral level, and proposes PIXE as an imaging modality to probe the quantitative distribution of metallic nanoparticles in tumors from experimental animal models with micrometer resolution. Copyright © 2017 Elsevier Inc. All rights reserved.

Safe use of iodinated and gadolinium-based contrast media in current practice in Japan: a questionnaire survey.

PubMed

Tsushima, Yoshito; Ishiguchi, Tsuneo; Murakami, Takamichi; Hayashi, Hiromitsu; Hayakawa, Katsumi; Fukuda, Kunihiko; Korogi, Yukunori; Sugimoto, Hideharu; Takehara, Yasuo; Narumi, Yoshifumi; Arai, Yasuaki; Kuwatsuru, Ryohei; Yoshimitsu, Kengo; Awai, Kazuo; Kanematsu, Masayuki; Takagi, Ryo

2016-02-01

To help establish consensus on the safe use of contrast media in Japan. Questionnaires were sent to accredited teaching hospitals with radiology residency programs. The reply rate was 45.4% (329/724). For contrast-induced nephropathy (CIN), chronic and acute kidney diseases were considered a risk factor in 96.7 and 93.6%, respectively, and dehydration in 73.9%. As preventive actions, intravenous hydration (89.1%) and reduction of iodinated contrast media dose (86.9%) were commonly performed. For nephrogenic systemic fibrosis (NSF), chronic and acute kidney diseases were considered risk factors in 98.5 and 90.6%, respectively, but use of unstable gadolinium-based contrast media was considered a risk factor in only 55.6%. A renal function test was always (63.5% in iodinated; 65.7% in gadolinium) or almost always (23.1; 19.8%) performed, and estimated glomerular filtration rate (eGFR) was the parameter most frequently used (80.8; 82.6%). For the patients with risk factors for acute adverse reaction (AAR), steroid premedication or/and change of contrast medium were frequent preventive actions, but intravenous steroid administration immediately before contrast media use was still performed. Our questionnaire survey revealed that preventive actions against CIN were properly performed based on patients' eGFR. Preventive actions against NSF and AAR still lacked consensus.

Cognitive inhibition in students with and without dyslexia and dyscalculia.

PubMed

Wang, Li-Chih; Tasi, Hung-Ju; Yang, Hsien-Ming

2012-01-01

The present study presents a comparison of the cognitive inhibition abilities of dyslexic, dyscalculic, and control students. The participants were 45 dyslexic students, 45 dyscalculic students, and 45 age-, gender-, and IQ-matched control students. The major evaluation tools included six cognitive inhibition tasks which were restructured during principal component analysis into three categories: graph inhibition, number inhibition, and word inhibition. Comparisons of the 3 groups of students revealed that in graph inhibition, dyscalculic students performed worst of the 3 groups, with dyslexic students also performing worse than control students in this category. For number inhibition, the control students' performances were equal to those of dyslexic students, with both groups performing better than dyscalculic students. For word inhibition, control students' performances were equal to those of dyscalculic students; both groups had shorter response times and lower incorrect rates than dyslexic students. These results suggest the complexity of the different cognitive inhibition abilities displayed by dyslexic, dyscalculic, and control students. However, some regular patterns occurred. Copyright © 2012 Elsevier Ltd. All rights reserved.

Survey of gadolinium-based contrast agent utilization among the members of the Society for Pediatric Radiology: a Quality and Safety Committee report.

PubMed

Blumfield, Einat; Moore, Michael M; Drake, Mary K; Goodman, Thomas R; Lewis, Kristopher N; Meyer, Laura T; Ngo, Thang D; Sammet, Christina; Stanescu, Arta Luana; Swenson, David W; Slovis, Thomas L; Iyer, Ramesh S

2017-05-01

Gadolinium-based contrast agents (GBCAs) have been used for magnetic resonance (MR) imaging over the last three decades. Recent reports demonstrated gadolinium retention in patients' brains following intravenous administration. Since gadolinium is a highly toxic heavy metal, there is a potential for adverse effects from prolonged retention or deposition, particularly in children. For this reason, the Society (SPR) for Pediatric Radiology Quality and Safety committee conducted a survey to evaluate the current status of GBCAs usage among pediatric radiologists. To assess the usage of GBCAs among SPR members. An online 15-question survey was distributed to SPR members. Survey questions pertained to the type of GBCAs used, protocoling workflow, requirement of renal function or pregnancy tests, and various clinical indications for contrast-enhanced MRI examinations. A total of 163 survey responses were compiled (11.1% of survey invitations), the majority of these from academic institutions in the United States. Ninety-four percent reported that MR studies are always or usually protocoled by pediatric radiologists. The most common GBCA utilized by survey respondents were Eovist (60.7%), Ablavar (45.4%), Gadovist (38.7%), Magnevist (34.4%) and Dotarem (32.5%). For several clinical indications, survey responses regarding GBCA administration were concordant with American College of Radiology (ACR) Appropriateness Criteria, including seizures, headache and osteomyelitis. For other indications, including growth hormone deficiency and suspected vascular ring, survey responses revealed potential overutilization of GBCAs when compared to ACR recommendations. Survey results demonstrate that GBCAs are administered judiciously in children, yet there is an opportunity to improve their utilization with the goal of reducing potential future adverse effects.

Tumor Xenograft Response to Redox-Active Therapies Assessed by Magnetic Resonance Imaging Using a Thiol-Bearing DOTA Complex of Gadolinium1

PubMed Central

Guntle, Gerald P; Jagadish, Bhumasamudram; Mash, Eugene A; Powis, Garth; Dorr, Robert T; Raghunand, Natarajan

2012-01-01

Gd-LC6-SH is a thiol-bearing DOTA complex of gadolinium designed to bind plasma albumin at the conserved Cys34 site. The binding of Gd-LC6-SH shows sensitivity to the presence of competing thiols. We hypothesized that Gd-LC6-SH could provide magnetic resonance imaging (MRI) enhancement that is sensitive to tumor redox state and that the prolonged retention of albumin-bound Gd-LC6-SH in vivo can be exploited to identify a saturating dose above which the shortening of MRI longitudinal relaxation time (T1) of tissue is insensitive to the injected gadolinium dose. In the Mia-PaCa-2 pancreatic tumor xenograft model in SCID mice, both the small-molecule Gd-DTPA-BMA and the macromolecule Galbumin MRI contrast agents produced dose-dependent decreases in tumor T1. By contrast, the decreases in tumor T1 provided by Gd-LC6-SH at 0.05 and 0.1 mmol/kg were not significantly different at longer times after injection. SCID mice bearing Mia-PaCa-2 or NCI-N87 tumor xenografts were treated with either the glutathione synthesis inhibitor buthionine sulfoximine or the thiol-oxidizing anticancer drug Imexon, respectively. In both models, there was a significantly greater increase in tumor R1 (=1/T1) 60 minutes after injection of Gd-LC6-SH in drug-treated animals relative to saline-treated controls. In addition, Mercury Orange staining for nonprotein sulfhydryls was significantly decreased by drug treatment relative to controls in both tumor models. In summary, these studies show that thiol-bearing complexes of gadolinium such as Gd-LC6-SH can serve as redox-sensitive MRI contrast agents for detecting differences in tumor redox status and can be used to evaluate the effects of redox-active drugs. PMID:22741038

Fabrication and in vitro characterization of gadolinium-based nanoclusters for simultaneous drug delivery and radiation enhancement

NASA Astrophysics Data System (ADS)

Yoo, Shannon S.; Guo, Linghong; Sun, Xuejun; Shaw, Andrew R.; Yuan, Zhipeng; Löbenberg, Raimar; Roa, Wilson H.

2016-09-01

We report the synthesis of a gadolinium hydroxide (Gd(OH)3) nanorod based doxorubicin (Dox) delivery system that can enhance both magnetic resonance imaging contrast and radiation sensitivity. A simple and cost effective wet-chemical method was utilized in the presence of manganese (Mn) ions and Dox to produce the Gd(OH)3:Mn·Dox nanocluster structure. The Gd(OH)3:Mn·Dox nanocluster was composed of Mn-doped Gd(OH)3 nanorods arranged in parallel with Dox as a linker molecule between the adjacent nanorods. No other studies have utilized Dox as both the linker and therapeutic molecule in a nanostructure to date. The Gd(OH)3 nanorod is reported to have no significant cellular or in vivo toxicity, which makes it an ideal base material for this biomedical application. The Gd(OH)3:Mn·Dox nanocluster exhibited paramagnetic behavior and was stable in a colloidal solution. The nanocluster also enabled high Dox loading capacity and specifically released Dox in a sustained and pH-dependent manner. The positively charged Gd(OH)3:Mn·Dox nanoclusters were readily internalized into MDA-MB-231 breast cancer cells via endocytosis, which resulted in intracellular release of Dox. The released Dox in cells was effective in conferring cytotoxicity and inhibiting proliferation of cancer cells. Furthermore, a synergistic anticancer effect could be observed with radiation treatment. Overall, the Gd(OH)3:Mn·Dox nanocluster drug delivery system described herein may have potential utility in clinics as a multifunctional theranostic nanoparticle with combined benefits in both diagnosis and therapy in the management of cancer.

Target binding improves relaxivity in aptamer-gadolinium conjugates.

PubMed

Bernard, Elyse D; Beking, Michael A; Rajamanickam, Karunanithi; Tsai, Eve C; Derosa, Maria C

2012-12-01

MRI contrast agents (CA) have been heavily used over the past several decades to enhance the diagnostic value of the obtained images. From a design perspective, two avenues to improve the efficacy of contrast agents are readily evident: optimization of magnetic properties of the CA, and optimization of the pharmacokinetics and distribution of the CA in the patient. Contrast agents consisting of DNA aptamer-gadolinium(III) conjugates provide a single system in which these factors can be addressed simultaneously. In this proof-of-concept study, the 15mer thrombin aptamer was conjugated to diethylenetriaminepentaacetic (DTPA) dianhydride to form a monoamide derivative of the linear open-chain chelate present in the commonly used contrast agent Magnevist(®). The stability of the conjugated DNA aptamer-DTPA-Gd(III) chelate in a transmetallation study using Zn(II) was found to be similar to that reported for DTPA-Gd(III). Relaxivity enhancements of 35 ± 4 and 20 ± 1 % were observed in the presence of thrombin compared to a control protein at fields of 9.4 and 1.5 T, respectively. The inclusion of spacers between the aptamer and the DTPA to eliminate possible steric effects was also investigated but not found to improve the relaxation enhancement achieved in comparison to the unaltered aptamer conjugate.

A pyrophosphate-responsive gadolinium(III) MRI contrast agent.

PubMed

Surman, Andrew J; Bonnet, Célia S; Lowe, Mark P; Kenny, Gavin D; Bell, Jimmy D; Tóth, Eva; Vilar, Ramon

2011-01-03

This study shows that the relaxivity and optical properties of functionalised lanthanide-DTPA-bis-amide complexes (lanthanide=Gd(3+) and Eu(3+) , DTPA=diethylene triamine pentaacetic acid) can be successfully modulated by addition of specific anions, without direct Ln(3+) /anion coordination. Zinc(II)-dipicolylamine moieties, which are known to bind strongly to phosphates, were introduced in the amide "arms" of these ligands, and the interaction of the resulting Gd-Zn(2) complexes with a range of anions was screened by using indicator displacement assays (IDAs). Considerable selectivity for polyphosphorylated species (such as pyrophosphate and adenosine-5'-triphosphate (ATP)) over a range of other anions (including monophosphorylated anions) was apparent. In addition, we show that pyrophosphate modulates the relaxivity of the gadolinium(III) complex, this modulation being sufficiently large to be observed in imaging experiments. To establish the binding mode of the pyrophosphate and gain insight into the origin of the relaxometric modulation, a series of studies including UV/Vis and emission spectroscopy, luminescence lifetime measurements in H(2) O and D(2) O, (17) O and (31) P NMR spectroscopy and nuclear magnetic resonance dispersion (NMRD) studies were carried out. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of gadolinium doped titanium(IV) oxide and their photocatalytic activity to decrease chemical oxygen demand (COD) value of water pollutants

NASA Astrophysics Data System (ADS)

Eddy, Diana Rakhmawaty; Dwiyanti, Dina; Rahayu, Iman; Hastiawan, Iwan; Bahti, Husein H.

2017-05-01

Pesticides are widely used for the control of plant disease. Unfortunately they are highly toxic to terraneous and aquatic life; this is a particular problem in agricultural areas. TiO2 is widely used for pesticide control because of its photocatalytic activity, but it still has inadequacy in its wide band gap. Alternatively, the wide band gap of TiO2 could be narrowed by modification with rare earth element such as gadolinium, so the photocatalytic activity of TiO2could be significantly enhanced. The purpose of this experiment is to synthesize Gd/TiO2 and its application to reduce COD of water pollutants such as carbosulfan pesticide. This experiment is done by doping gadolinium oxide into titanium tetra isopropoxide by sol-gel method. The crystal structure is characterized by using XRD, shown anatase successfully obtained with the smallest crystallite size is 37.655 nm, indicated optimum calcination time is 4 hours. SEM-EDX result shown morphology of crystal is big aggregates. Photocatalytic activity is tested to carbosulfan pesticide, obtained the COD percent decreases up to 87.88%.

Controllable Fabrication and Optical Properties of Uniform Gadolinium Oxysulfate Hollow Spheres

PubMed Central

Chen, Fashen; Chen, Gen; Liu, Tao; Zhang, Ning; Liu, Xiaohe; Luo, Hongmei; Li, Junhui; Chen, Limiao; Ma, Renzhi; Qiu, Guanzhou

2015-01-01

Uniform gadolinium oxysulfate (Gd2O2SO4) hollow spheres were successfully fabricated by calcination of corresponding Gd-organic precursor obtained via a facile hydrothermal process. The Gd2O2SO4 hollow spheres have a mean diameter of approximately 550 nm and shell thickness in the range of 30–70 nm. The sizes and morphologies of as-prepared Gd2O2SO4 hollow spheres could be deliberately controlled by adjusting the experimental parameters. Eu-doped Gd2O2SO4 hollow spheres have also been prepared for the property modification and practical applications. The structure, morphology, and properties of as-prepared products were characterized by XRD, TEM, HRTEM, SEM and fluorescence spectrophotometer. Excited with ultraviolet (UV) pump laser, successful downconversion (DC) could be achieved for Eu-doped Gd2O2SO4 hollow spheres. PMID:26671661

Caustic Precipitation of Plutonium Using Gadolinium as the Neutron Poison for Disposition to High Level Waste

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bronikowski, M.G.

2002-06-24

Nuclear Materials Management Division (NMMD) has proposed that up to 100 kg of the plutonium (Pu) solutions stored in H-Canyon be precipitated with a nuclear poison and dispositioned to H-Area Tank Farm. The use of gadolinium (Gd) as the poison would greatly reduce the number of additional glass logs resulting from this disposition. This report summarizes the characteristics of the precipitation process and addresses criticality concerns in the Nuclear Criticality Safety Evaluation. No problems were found with the nature of the precipitate or the neutralization process.

Galectin-3 Inhibits Galectin-8/Parkin-Mediated Ubiquitination of Group A Streptococcus.

PubMed

Cheng, Yi-Lin; Wu, Yan-Wei; Kuo, Chih-Feng; Lu, Shiou-Ling; Liu, Fu-Tong; Anderson, Robert; Lin, Chiou-Feng; Liu, Yi-Ling; Wang, Wan-Yu; Chen, Ying-Da; Zheng, Po-Xing; Wu, Jiunn-Jong; Lin, Yee-Shin

2017-07-25

Group A streptococcus (GAS) is an important human pathogen that causes a wide variety of cutaneous and systemic infections. Although originally thought to be an extracellular bacterium, numerous studies have demonstrated that GAS can trigger internalization into nonimmune cells to escape from immune surveillance or antibiotic-mediated killing. Epithelial cells possess a defense mechanism involving autophagy-mediated targeting and killing of GAS within lysosome-fused autophagosomes. In endothelial cells, in contrast, we previously showed that autophagy is not sufficient for GAS killing. In the present study, we showed higher galectin-3 (Gal-3) expression and lower Gal-8 expression in endothelial cells than in epithelial cells. The recruitment of Gal-3 to GAS is higher and the recruitment of Gal-8 to GAS is lower in endothelial cells than in epithelial cells. We further showed that Gal-3 promotes GAS replication and diminishes the recruitment of Gal-8 and ubiquitin, the latter of which is a critical protein for autophagy sequestration. After knockdown of Gal-3 in endothelial cells, the colocalization of Gal-8, parkin, and ubiquitin-decorated GAS is significantly increased, as is the interaction of Gal-8 and parkin, an E3 ligase. Furthermore, inhibition of Gal-8 in epithelial cells attenuates recruitment of parkin; both Gal-8 and parkin contribute to ubiquitin recruitment and GAS elimination. Animal studies confirmed that Gal-3-knockout mice develop less-severe skin damage and that GAS replication can be detected only in the air pouch and not in organs and endothelial cells. These results demonstrate that Gal-3 inhibits ubiquitin recruitment by blocking Gal-8 and parkin recruitment, resulting in GAS replication in endothelial cells. IMPORTANCE In epithelial cells, GAS can be efficiently killed within the lysosome-fused autophaosome compartment. However, we previously showed that, in spite of LC-3 recruitment, the autophagic machinery is not sufficient for GAS killing

Mutants in three novel complementation groups inhibit membrane protein insertion into and soluble protein translocation across the endoplasmic reticulum membrane of Saccharomyces cerevisiae

PubMed Central

1992-01-01

We have isolated mutants that inhibit membrane protein insertion into the ER membrane of Saccharomyces cerevisiae. The mutants were contained in three complementation groups, which we have named SEC70, SEC71, and SEC72. The mutants also inhibited the translocation of soluble proteins into the lumen of the ER, indicating that they pleiotropically affect protein transport across and insertion into the ER membrane. Surprisingly, the mutants inhibited the translocation and insertion of different proteins to drastically different degrees. We have also shown that mutations in SEC61 and SEC63, which were previously isolated as mutants inhibiting the translocation of soluble proteins, also affect the insertion of membrane proteins into the ER. Taken together our data indicate that the process of protein translocation across the ER membrane involves a much larger number of gene products than previously appreciated. Moreover, different translocation substrates appear to have different requirements for components of the cellular targeting and translocation apparatus. PMID:1730771

Effects of iodinated contrast agent, xylocaine and gadolinium concentration on the signal emitted in magnetic resonance arthrography: a samples study*

PubMed Central

da Silva, Yvana Lopes Pinheiro; Costa, Rita Zanlorensi Visneck; Pinho, Kátia Elisa Prus; Ferreira, Ricardo Rabello; Schuindt, Sueliton Miyamoto

2015-01-01

Objective To investigate the effects of dilution of paramagnetic contrast agent with iodinated contrast and xylocaine on the signal intensity during magnetic resonance arthrography, and to improve the paramagnetic contrast agent concentration utilized in this imaging modality. Materials and Methods Samples specially prepared for the study with three different concentrations of paramagnetic contrast agent diluted in saline, iodinated contrast agent and xylocaine were imaged with fast spin echo T1-weighted sequences with fat saturation. The samples were placed into flasks and graphical analysis of the signal intensity was performed as a function of the paramagnetic contrast concentration. Results As compared with samples of equal concentrations diluted only with saline, the authors have observed an average signal intensity decrease of 20.67% for iodinated contrast agent, and of 28.34% for xylocaine. However, the increased gadolinium concentration in the samples caused decrease in signal intensity with all the dilutions. Conclusion Minimizing the use of iodinated contrast media and xylocaine and/or the use of a gadolinium concentration of 2.5 mmol/L diluted in saline will improve the sensitivity of magnetic resonance arthrography. PMID:25987746

Diagnostic value of three-dimensional magnetic resonance imaging of inner ear after intratympanic gadolinium injection, and clinical application of magnetic resonance imaging scoring system in patients with delayed endolymphatic hydrops.

PubMed

Gu, X; Fang, Z-M; Liu, Y; Lin, S-L; Han, B; Zhang, R; Chen, X

2014-01-01

Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging of the inner ear after intratympanic injection of gadolinium, together with magnetic resonance imaging scoring of the perilymphatic space, were used to investigate the positive identification rate of hydrops and determine the technique's diagnostic value for delayed endolymphatic hydrops. Twenty-five patients with delayed endolymphatic hydrops underwent pure tone audiometry, bithermal caloric testing, vestibular-evoked myogenic potential testing and three-dimensional magnetic resonance imaging of the inner ear after bilateral intratympanic injection of gadolinium. The perilymphatic space of the scanned images was analysed to investigate the positive identification rate of endolymphatic hydrops. According to the magnetic resonance imaging scoring of the perilymphatic space and the diagnostic standard, 84 per cent of the patients examined had endolymphatic hydrops. In comparison, the positive identification rates for vestibular-evoked myogenic potential and bithermal caloric testing were 52 per cent and 72 per cent respectively. Three-dimensional magnetic resonance imaging after intratympanic injection of gadolinium is valuable in the diagnosis of delayed endolymphatic hydrops and its classification. The perilymphatic space scoring system improved the diagnostic accuracy of magnetic resonance imaging.

An unconventional origin of metal-ion rescue and inhibition in the Tetrahymena group I ribozyme reaction.

PubMed Central

Shan, S O; Herschlag, D

2000-01-01

The presence of catalytic metal ions in RNA active sites has often been inferred from metal-ion rescue of modified substrates and sometimes from inhibitory effects of alternative metal ions. Herein we report that, in the Tetrahymena group I ribozyme reaction, the deleterious effect of a thio substitution at the pro-Sp position of the reactive phosphoryl group is rescued by Mn2+. However, analysis of the reaction of this thio substrate and of substrates with other modifications strongly suggest that this rescue does not stem from a direct Mn2+ interaction with the Sp sulfur. Instead, the apparent rescue arises from a Mn2+ ion interacting with the residue immediately 3' of the cleavage site, A(+1), that stabilizes the tertiary interactions between the oligonucleotide substrate (S) and the active site. This metal site is referred to as site D herein. We also present evidence that a previously observed Ca2+ ion that inhibits the chemical step binds to metal site D. These and other observations suggest that, whereas the interactions of Mn2+ at site D are favorable for the chemical reaction, the Ca2+ at site D exerts its inhibitory effect by disrupting the alignment of the substrates within the active site. These results emphasize the vigilance necessary in the design and interpretation of metal-ion rescue and inhibition experiments. Conversely, in-depth mechanistic analysis of the effects of site-specific substrate modifications can allow the effects of specific metal ion-RNA interactions to be revealed and the properties of individual metal-ion sites to be probed, even within the sea of metal ions bound to RNA. PMID:10864040

Diagnosis of Bell palsy with gadolinium magnetic resonance imaging.

PubMed

Becelli, R; Perugini, M; Carboni, A; Renzi, G

2003-01-01

Bell palsy is a condition resulting from a peripheral edematous compression on the nervous fibers of the facial nerve. This pathological condition often has clinical characteristics of no importance and spontaneously disappears in a short time in a high percentage of cases. Facial palsy concerning cranial nerve VII can also be caused by other conditions such as mastoid fracture, acoustic neurinoma, tumor spread to the temporal lobe (e.g., cholesteatoma), neoformation of the parotid gland, Melkersson-Rosenthal syndrome, and Ramsay-Hunt syndrome. Therefore, it is important to adopt an accurate diagnostic technique allowing the rapid detection of Bell palsy and the exclusion of causes of facial paralysis requiring surgical treatment. Magnetic resonance imaging (MRI) with medium contrast of the skull shows a marked increase in revealing lesions, even of small dimensions, inside the temporal bone and at the cerebellopontine angle. The authors present a clinical case to show the important role played by gadolinium MRI in reaching a diagnosis of Bell palsy in the differential diagnosis of the various conditions that determine paralysis of the facial nerve and in selecting the most suitable treatment or surgery to be adopted.

Activation of Plant Innate Immunity by Extracellular High Mobility Group Box 3 and Its Inhibition by Salicylic Acid

PubMed Central

Choi, Hyong Woo; Manohar, Murli; Manosalva, Patricia; Tian, Miaoying; Moreau, Magali; Klessig, Daniel F.

2016-01-01

Damage-associated molecular pattern molecules (DAMPs) signal the presence of tissue damage to induce immune responses in plants and animals. Here, we report that High Mobility Group Box 3 (HMGB3) is a novel plant DAMP. Extracellular HMGB3, through receptor-like kinases BAK1 and BKK1, induced hallmark innate immune responses, including i) MAPK activation, ii) defense-related gene expression, iii) callose deposition, and iv) enhanced resistance to Botrytis cinerea. Infection by necrotrophic B. cinerea released HMGB3 into the extracellular space (apoplast). Silencing HMGBs enhanced susceptibility to B. cinerea, while HMGB3 injection into apoplast restored resistance. Like its human counterpart, HMGB3 binds salicylic acid (SA), which results in inhibition of its DAMP activity. An SA-binding site mutant of HMGB3 retained its DAMP activity, which was no longer inhibited by SA, consistent with its reduced SA-binding activity. These results provide cross-kingdom evidence that HMGB proteins function as DAMPs and that SA is their conserved inhibitor. PMID:27007252

Gadolinium-enhanced MR images of the growing piglet skeleton: ionic versus nonionic contrast agent.

PubMed

Menezes, Nina M; Olear, Elizabeth A; Li, Xiaoming; Connolly, Susan A; Zurakowski, David; Foley, Mary; Shapiro, Frederic; Jaramillo, Diego

2006-05-01

To determine whether there are differences in the distribution of ionic and nonionic gadolinium-based contrast agents by evaluating contrast enhancement of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis in the knees of normal piglets. Following approval from the Subcommittee on Research Animal Care, knees of 12 3-week-old piglets were imaged at 3-T magnetic resonance (MR) imaging after intravenous injection of gadoteridol (nonionic contrast agent; n = 6) or gadopentetate dimeglumine (ionic contrast agent; n = 6). Early enhancement evaluation with gradient-echo MR imaging was quantified and compared (Student t test) by means of enhancement ratios. Distribution of contrast material was assessed and compared (Student t test) by means of T1 measurements obtained before and at three 15-minute intervals after contrast agent administration. The relative visibility of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis was qualitatively assessed by two observers and compared (Wilcoxon signed rank test). Differences in matrix content and cellularity that might explain the imaging findings were studied at histologic evaluation. Enhancement ratios were significantly higher for gadoteridol than for gadopentetate dimeglumine in the physis, epiphyseal cartilage, and secondary ossification center (P < .05). After contrast agent administration, T1 values decreased sharply for both agents-but more so for gadoteridol. Additionally, there was less variability in T1 values across structures with this contrast agent. Gadoteridol resulted in greater visibility of the physis, while gadopentetate dimeglumine resulted in greater contrast between the physis and metaphysis (P < .05). The results suggest different roles for the two gadolinium-based contrast agents: The nonionic contrast medium is better suited for evaluating perfusion and anatomic definition in the immature skeleton, while the ionic contrast medium is better for

Gadolinium-enhanced magnetic resonance angiography in renal artery stenosis: comparison with digital subtraction angiography.

PubMed

Law, Y M; Tay, K H; Gan, Y U; Cheah, F K; Tan, B S

2008-04-01

To evaluate the accuracy of gadolinium-enhanced magnetic resonance angiography in assessing renal artery stenosis compared to catheter digital subtraction angiography. Retrospective study. Singapore General Hospital. Records of patients who underwent magnetic resonance angiography as well as digital subtraction angiography for assessment of renal artery stenosis from January 2003 to December 2005 were reviewed. There were 27 patients (14 male, 13 female) with a mean age of 62 (range, 44-77) years. There were 10 patients with renal transplants; their native renal arteries were not evaluated. Each of the two experienced interventional and body magnetic resonance radiologists, who were blinded to the results, reviewed the digital subtraction angiography and magnetic resonance angiography images respectively. Digital subtraction angiography was used as the standard of reference. A total of 39 renal arteries from these 27 patients were evaluated. One of the arteries was previously stented and could not be assessed with magnetic resonance angiography due to severe artefacts. Of the remaining 38 renal arteries, two were graded as normal, seven as having mild stenosis (<50%), eight as having moderate stenosis (> or =50% but <75%), and 21 as having severe stenosis (> or =75%). Magnetic resonance angiography and digital subtraction angiography were concordant in 89% of the arteries; magnetic resonance angiography overestimated the degree of stenosis in 8% and underestimated it in 3% of them. In the evaluation of clinically significant renal artery stenosis (> or =50%) with magnetic resonance angiography, the overall sensitivity, specificity, positive predictive value, and negative predictive value were 97%, 67%, 90%, and 86% respectively. The sensitivity and specificity of magnetic resonance angiography in transplant renal artery stenosis was 100%. CONCLUSION. Our experience suggested that gadolinium-enhanced magnetic resonance angiography is a sensitive non

Antisense oligonucleotides effectively inhibit the co-transcriptional splicing of a Candida group I intron in vitro and in vivo: Implications for antifungal therapeutics.

PubMed

Zhang, Libin; Leibowitz, Michael J; Zhang, Yi

2009-02-18

Self-splicing of group I intron from the 26S rRNA of Candida albicans is essential for maturation of the host RNA. Here, we demonstrated that the co-transcriptional splicing of the intron in vitro was blocked by antisense oligonucleotides (AONs) targeting the P3-P7 core of the intron. The core-targeted AON effectively and specifically inhibited the intron splicing from its host RNA in living C. albicans. Furthermore, flow cytometry experiments showed that the growth inhibition was caused by a fungicidal effect. For the first time, we showed that an AON targeting the ribozyme core folding specifically inhibits the endogenous ribozyme splicing in living cells and specifically kills the intron-containing fungal strains, which sheds light on the development of antifungal drugs in the future.

Gadolinium-based compounds induce NLRP3-dependent IL-1β production and peritoneal inflammation.

PubMed

Schmidt-Lauber, Christian; Bossaller, Lukas; Abujudeh, Hani H; Vladimer, Gregory I; Christ, Anette; Fitzgerald, Katherine A; Latz, Eicke; Gravallese, Ellen M; Marshak-Rothstein, Ann; Kay, Jonathan

2015-11-01

Nephrogenic systemic fibrosis (NSF) is a progressive fibrosing disorder that may develop in patients with chronic kidney disease after administration of gadolinium (Gd)-based contrast agents (GBCAs). In the setting of impaired renal clearance of GBCAs, Gd deposits in various tissues and fibrosis subsequently develops. However, the precise mechanism by which fibrosis occurs in NSF is incompletely understood. Because other profibrotic agents, such as silica or asbestos, activate the nucleotide-binding oligomerisation domain (NOD)-like receptor protein 3 (NLRP3) inflammasome and initiate interleukin (IL)-1β release with the subsequent development of fibrosis, we evaluated the effects of GBCAs on inflammasome activation. Bone marrow derived macrophages from C57BL/6, Nlrp3(-/-) and Asc(-/-) mice were incubated with three Gd-containing compounds and IL-1β activation and secretion was detected by ELISA and western blot analysis. Inflammasome activation and regulation was investigated in IL-4- and interferon (IFN)γ-polarised macrophages by ELISA, quantitative real time (qRT)-PCR and NanoString nCounter analysis. Furthermore, C57BL/6 and Nlrp3(-/-)mice were intraperitoneally injected with GBCA and recruitment of inflammatory cells to the peritoneum was analysed by fluorescence-activated cell sorting (FACS). Free Gd and GBCAs activate the NLRP3 inflammasome and induce IL-1β secretion in vitro. Gd-diethylenetriaminepentaacetic acid also induces the recruitment of neutrophils and inflammatory monocytes to the peritoneum in vivo. Gd activated IL-4-polarised macrophages more effectively than IFNγ-polarised macrophages, which preferentially expressed genes known to downregulate inflammasome activity. These data suggest that Gd released from GBCAs triggers a NLRP3 inflammasome-dependent inflammatory response that leads to fibrosis in an appropriate clinical setting. The preferential activation of IL-4-differentiated macrophages is consistent with the predominantly fibrotic

Investigating phase transition temperatures of size separated gadolinium silicide magnetic nanoparticles

DOE PAGES

Hunagund, Shivakumar G.; Harstad, Shane M.; El-Gendy, Ahmed A.; ...

2018-01-11

Gadolinium silicide (Gd 5Si 4) nanoparticles (NPs) exhibit different properties compared to their parent bulk materials due to finite size, shape, and surface effects. NPs were prepared by high energy ball-milling of the as-cast Gd 5Si 4 ingot and size separated into eight fractions using time sensitive sedimentation in an applied dc magnetic field with average particle sizes ranging from 700 nm to 82 nm. The largest Gd 5Si 4 NPs order ferromagnetically at 316 K. A second anomaly observed at 110 K can be ascribed to a Gd 5Si 3 impurity. Here as the particle sizes decrease, the volumemore » fraction of Gd 5Si 3 phase increases at the expense of the Gd 5Si 4 phase, and the ferromagnetic transition temperature of Gd 5Si 4 is reduced from 316 K to 310 K, while the ordering of the minor phase is independent of the particle size, remaining at 110 K.« less

Investigating phase transition temperatures of size separated gadolinium silicide magnetic nanoparticles

NASA Astrophysics Data System (ADS)

Hunagund, Shivakumar G.; Harstad, Shane M.; El-Gendy, Ahmed A.; Gupta, Shalabh; Pecharsky, Vitalij K.; Hadimani, Ravi L.

2018-05-01

Gadolinium silicide (Gd5Si4) nanoparticles (NPs) exhibit different properties compared to their parent bulk materials due to finite size, shape, and surface effects. NPs were prepared by high energy ball-milling of the as-cast Gd5Si4 ingot and size separated into eight fractions using time sensitive sedimentation in an applied dc magnetic field with average particle sizes ranging from 700 nm to 82 nm. The largest Gd5Si4 NPs order ferromagnetically at 316 K. A second anomaly observed at 110 K can be ascribed to a Gd5Si3 impurity. As the particle sizes decrease, the volume fraction of Gd5Si3 phase increases at the expense of the Gd5Si4 phase, and the ferromagnetic transition temperature of Gd5Si4 is reduced from 316 K to 310 K, while the ordering of the minor phase is independent of the particle size, remaining at 110 K.

Investigating phase transition temperatures of size separated gadolinium silicide magnetic nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hunagund, Shivakumar G.; Harstad, Shane M.; El-Gendy, Ahmed A.

Gadolinium silicide (Gd 5Si 4) nanoparticles (NPs) exhibit different properties compared to their parent bulk materials due to finite size, shape, and surface effects. NPs were prepared by high energy ball-milling of the as-cast Gd 5Si 4 ingot and size separated into eight fractions using time sensitive sedimentation in an applied dc magnetic field with average particle sizes ranging from 700 nm to 82 nm. The largest Gd 5Si 4 NPs order ferromagnetically at 316 K. A second anomaly observed at 110 K can be ascribed to a Gd 5Si 3 impurity. Here as the particle sizes decrease, the volumemore » fraction of Gd 5Si 3 phase increases at the expense of the Gd 5Si 4 phase, and the ferromagnetic transition temperature of Gd 5Si 4 is reduced from 316 K to 310 K, while the ordering of the minor phase is independent of the particle size, remaining at 110 K.« less

Monte Carlo calculations of thermal neutron capture in gadolinium: a comparison of GEANT4 and MCNP with measurements.

PubMed

Enger, Shirin A; Munck af Rosenschöld, Per; Rezaei, Arash; Lundqvist, Hans

2006-02-01

GEANT4 is a Monte Carlo code originally implemented for high-energy physics applications and is well known for particle transport at high energies. The capacity of GEANT4 to simulate neutron transport in the thermal energy region is not equally well known. The aim of this article is to compare MCNP, a code commonly used in low energy neutron transport calculations and GEANT4 with experimental results and select the suitable code for gadolinium neutron capture applications. To account for the thermal neutron scattering from chemically bound atoms [S(alpha,beta)] in biological materials a comparison of thermal neutron fluence in tissue-like poly(methylmethacrylate) phantom is made with MCNP4B, GEANT4 6.0 patch1, and measurements from the neutron capture therapy (NCT) facility at the Studsvik, Sweden. The fluence measurements agreed with MCNP calculated results considering S(alpha,beta). The location of the thermal neutron peak calculated with MCNP without S(alpha,beta) and GEANT4 is shifted by about 0.5 cm towards a shallower depth and is 25%-30% lower in amplitude. Dose distribution from the gadolinium neutron capture reaction is then simulated by MCNP and compared with measured data. The simulations made by MCNP agree well with experimental results. As long as thermal neutron scattering from chemically bound atoms are not included in GEANT4 it is not suitable for NCT applications.

MicroRNA-495 Inhibits Gastric Cancer Cell Migration and Invasion Possibly via Targeting High Mobility Group AT-Hook 2 (HMGA2).

PubMed

Wang, Huashe; Jiang, Zhipeng; Chen, Honglei; Wu, Xiaobin; Xiang, Jun; Peng, Junsheng

2017-02-04

BACKGROUND Gastric cancer is one of the most common malignancies, and has a high mortality rate. miR-495 acts as a suppressor in some cancers and HMGA2 (high mobility group AT-hook 2) is a facilitator for cell growth and epithelial-mesenchymal transition (EMT), but little is known about their effect in gastric cancer. This study aimed to investigate the role and mechanism of miR-495 in gastric cancer. MATERIAL AND METHODS miR-495 levels were quantitatively analyzed in gastric cancer tissue and GES-1, SGC-7901, BGC-823, and HGC-27 cell lines by qRT-PCR. Levels of miR-495 and HMGA2 were altered by cell transfection, after which cell migration and invasion were examined by Transwell and E-cadherin (CDH1); vimentin (VIM), and alpha smooth muscle actin (ACTA2) were detected by qRT-PCR and Western blotting. The interaction between miR-495 and HMGA2 was verified by dual-luciferase reporter assay. RESULTS miR-495 was significantly downregulated in cancer tissue and cell lines (p<0.05). Its overexpression inhibited cell migration and invasion, elevated CDH1, and inhibited VIM and ACTA2 levels in BGC-823 and HGC-27 cells. miR-495 directly inhibited HMGA2, which was upregulated in gastric cancer tissue, and promoted cell migration and invasion, inhibited CDH1, and elevated VIM and ACTA2. CONCLUSIONS miR-495 acts as a tumor suppressor in gastric cancer by inhibiting cell migration and invasion, which may be associated with its direct inhibition on HMGA2. These results suggest a promising therapeutic strategy for gastric cancer treatment.

In vitro cellular accumulation of gadolinium incorporated into chitosan nanoparticles designed for neutron-capture therapy of cancer.

PubMed

Shikata, Futoshi; Tokumitsu, Hiroyuki; Ichikawa, Hideki; Fukumori, Yoshinobu

2002-01-01

The accumulation of gadolinium loaded as gadopentetic acid (Gd-DTPA) in chitosan nanoparticles (Gd-nanoCPs), which were designed for gadolinium neutron-capture therapy (Gd-NCT) for cancer, was evaluated in vitro in cultured cells. Using L929 fibroblast cells, the Gd accumulation for 12 h at 37 degrees C was investigated at Gd concentrations lower than 40 ppm. The accumulation leveled above 20 ppm and reached 18.0+/-2.7 (mean+/-S.D.) microg Gd/10(6) cells at 40 ppm. Furthermore, the corresponding accumulations in B16F10 melanoma cells and SCC-VII squamous cell carcinoma, which were used in the previous Gd-NCT trials in vivo, were 27.1+/-2.9 and 59.8+/-9.8 microg Gd/10(6) cells, respectively, hence explaining the superior growth-suppression in the in vivo trials using SCC-VII cells. The accumulation of Gd-nanoCPs in these cells was 100-200 times higher in comparison to dimeglumine gadopentetate aqueous solution (Magnevist), a magnetic resonance imaging contrast agent. The endocytic uptake of Gd-nanoCPs, strongly holding Gd-DTPA, was suggested from transmission electron microscopy and comparative studies at 4 degrees C and with the solution system. These findings indicated that Gd-nanoCPs had a high affinity to the cells, probably contributing to the long retention of Gd in tumor tissue and leading to the significant suppression of tumor growth in the in vivo studies that were previously reported.

Short communication: possible mechanism for inhibiting the formation of polymers originated from 5-hydroxymethyl-2-furaldehyde by sulfite groups in the dairy thermal process.

PubMed

Guan, Yong-Guang; Zhu, Si-Ming; Yu, Shu-Juan; Xu, Xian-Bing; Zhu, Li-Cai

2013-05-01

5-Hydroxymethyl-2-furaldehyde can undergo polymerization to form high-molecular weight molecules via the Maillard reaction during dairy thermal treatment. In this study, the effect of sulfite group on polymer formation, especially in inhibiting the formation of high-molecular weight polymers has been described. Results showed that the sulfite group significantly inhibited the increase of polymer molecular weight via prevention of the polymerization of 5-hydroxymethyl-2-furaldehyde. The formation of an intermolecular dimer based on the glucose molecule through Schiff base cyclization can lead to a competitive reaction with 1,2-enolization to reduce 5-hydroxymethyl-2-furaldehyde formation, which might be another factor in reducing the formation of high-molecular weight polymers. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Inhibition of MMPs by alcohols

PubMed Central

Tezvergil-Mutluay, Arzu; Agee, Kelli A.; Hoshika, Tomohiro; Uchiyama, Toshikazu; Tjäderhane, Leo; Breschi, Lorenzo; Mazzoni, Annalisa; Thompson, Jeremy M.; McCracken, Courtney E.; Looney, Stephen W.; Tay, Franklin R.; Pashley, David H.

2011-01-01

Objectives While screening the activity of potential inhibitors of matrix metalloproteinases (MMPs), due to the limited water solubility of some of the compounds, they had to be solubilized in ethanol. When ethanol solvent controls were run, they were found to partially inhibit MMPs. Thus, the purpose of this study was to compare the MMP-inhibitory activity of a series of alcohols. Methods The possible inhibitory activity of a series of alcohols was measured against soluble rhMMP-9 and insoluble matrix-bound endogenous MMPs of dentin in completely demineralized dentin. Increasing concentrations (0.17, 0.86, 1.71 and 4.28 moles/L) of a homologous series of alcohols (i.e. methanol, ethanol, propanols, butanols, pentanols, hexanols, the ethanol ester of methacrylic acid, heptanols and octanol) were compared to ethanediol, and propanediol by regression analysis to calculate the molar concentration required to inhibit MMPs by 50% (i.e. the IC50). Results Using two different MMP models, alcohols were shown to inhibit rhMMP-9 and the endogenous proteases of dentin matrix in a dose-dependent manner. The degree of MMP inhibition by alcohols increased with chain length up to 4 methylene groups. Based on the molar concentration required to inhibit rhMMP-9 fifty percent, 2-hydroxyethylmethacrylate (HEMA), 3-hexanol, 3-heptanol and 1-octanol gave the strongest inhibition. Significance The results indicate that alcohols with 4 methylene groups inhibit MMPs more effectively than methanol or ethanol. MMP inhibition was inversely related to the Hoy's solubility parameter for hydrogen bonding forces of the alcohols (i.e. to their hydrophilicity). PMID:21676453

Anterior delayed gadolinium-enhanced MRI of cartilage values predict joint failure after periacetabular osteotomy.

PubMed

Kim, Sang Do; Jessel, Rebecca; Zurakowski, David; Millis, Michael B; Kim, Young-Jo

2012-12-01

Several available compositional MRIs seem to detect early osteoarthritis before radiographic appearance. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) has been most frequently used in clinical studies and reportedly predicts premature joint failure in patients undergoing Bernese periacetabular osteotomies (PAOs). We asked, given regional variations in biochemical composition in dysplastic hips, whether the dGEMRIC index of the anterior joint would better predict premature joint failure after PAOs than the coronal dGEMRIC index as previously reported. We retrospectively reviewed 43 hips in 41 patients who underwent Bernese PAO for hip dysplasia. Thirty-seven hips had preserved joints after PAOs and six were deemed premature failures based on pain, joint space narrowing, or subsequent THA. We used dGEMRIC to determine regional variations in biochemical composition. Preoperative demographic and clinical outcome score, radiographic measures of osteoarthritis and severity of dysplasia, and dGEMRIC indexes from different hip regions were analyzed in a multivariable regression analysis to determine the best predictor of premature joint failure. Minimum followup was 24 months (mean, 32 months; range, 24-46 months). The two cohorts were similar in age and sex distribution. Severity of dysplasia was similar as measured by lateral center-edge, anterior center-edge, and Tönnis angles. Preoperative pain, joint space width, Tönnis grade, and coronal and sagittal dGEMRIC indexes differed between groups. The dGEMRIC index in the anterior weightbearing region of the hip was lower in the prematurely failed group and was the best predictor. Success of PAO depends on the amount of preoperative osteoarthritis. These degenerative changes are seen most commonly in the anterior joint. The dGEMRIC index of the anterior joint may better predict premature joint failure than radiographic measures of hip osteoarthritis and coronal dGEMRIC index. Level II, prognostic study. See

Anticonvulsants Based on the α-Substituted Amide Group Pharmacophore Bind to and Inhibit Function of Neuronal Nicotinic Acetylcholine Receptors.

PubMed

Krivoshein, Arcadius V

2016-03-16

Although the antiepileptic properties of α-substituted lactams, acetamides, and cyclic imides have been known for over 60 years, the mechanism by which they act remains unclear. I report here that these compounds bind to the nicotinic acetylcholine receptor (nAChR) and inhibit its function. Using transient kinetic measurements with functionally active, nondesensitized receptors, I have discovered that (i) α-substituted lactams and cyclic imides are noncompetitive inhibitors of heteromeric subtypes (such as α4β2 and α3β4) of neuronal nAChRs and (ii) the binding affinity of these compounds toward the nAChR correlates with their potency in preventing maximal electroshock (MES)-induced convulsions in mice. Based on the hypothesis that α-substituted amide group is the essential pharmacophore of these drugs, I found and tested a simple compound, 2-phenylbutyramide. This compound indeed inhibits nAChR and shows good anticonvulsant activity in mice. Molecular docking simulations suggest that α-substituted lactams, acetamides, and cyclic imides bind to the same sites on the extracellular domain of the receptor. These new findings indicate that inhibition of brain nAChRs may play an important role in the action of these antiepileptic drugs, a role that has not been previously recognized.

The anti-inflammatory activity of standard aqueous stem bark extract of Mangifera indica L. as evident in inhibition of Group IA sPLA2.

PubMed

Dhananjaya, Bhadrapura Lakkappa; Shivalingaiah, Sudharshan

2016-03-01

The standard aqueous stem bark extract is consumed as herbal drink and used in the pharmaceutical formulations to treat patients suffering from various disease conditions in Cuba. This study was carried out to evaluate the modulatory effect of standard aqueous bark extract of M. indica on Group IA sPLA2. M. indica extract, dose dependently inhibited the GIA sPLA2 (NN-XIa-PLA2) activity with an IC50 value 8.1 µg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 98% at ~40 µg/ml concentration and at various concentrations (0-50 µg/ml), it dose dependently inhibited the edema formation. When examined as a function of increased substrate and calcium concentration, there was no relieve of inhibitory effect on the GIA sPLA2. Furthermore, the inhibition was irreversible as evidenced from binding studies. It is observed that the aqueous extract ofM. indica effectively inhibits sPLA2 and it is associated inflammatory activities, which substantiate their anti-inflammatory properties. The mode of inhibition could be due to direct interaction of components present in the extract, with sPLA2 enzyme. Further studies on understanding the principal constituents, responsible for the anti-inflammatory activity would be interesting to develop this into potent anti-inflammatory agent.

The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease.

PubMed

Moon, James C; Sheppard, Mary; Reed, Emma; Lee, Phillip; Elliott, Perry M; Pennell, Dudley J

2006-01-01

Anderson-Fabry Disease (AFD) is a storage disease that mimics hypertrophic cardiomyopathy. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance occurs in approximately 50% of patients in the basal inferolateral LV wall, but how an intracellular storage disease causes focal LGE is unknown. We present a whole-heart histological validation that LGE is caused by focal myocardial collagen scarring. This scarring may be the substrate for electrical re-entry and sudden arrhythmic death. The reasons for this distribution of fibrosis are unclear, but may reflect inhomogeneous left ventricular wall stress.

Synthesis of bulk-size transparent gadolinium oxide–polymer nanocomposites for gamma ray spectroscopy

PubMed Central

Cai, Wen; Chen, Qi; Cherepy, Nerine; Dooraghi, Alex; Kishpaugh, David; Chatziioannou, Arion; Payne, Stephen; Xiang, Weidong

2015-01-01

Heavy element loaded polymer composites have long been proposed to detect high energy X- and γ-rays upon scintillation. The previously reported bulk composite scintillators have achieved limited success because of the diminished light output resulting from fluorescence quenching and opacity. We demonstrate the synthesis of a transparent nanocomposite comprising gadolinium oxide nanocrystals uniformly dispersed in bulk-size samples at a high loading content. The strategy to avoid luminescence quenching and opacity in the nanocomposite was successfully deployed, which led to the radioluminescence light yield of up to 27 000/MeV, about twice as much as standard commercial plastic scintillators. Nanocomposites monoliths (14 mm diameter by 3 mm thickness) with 31 wt% loading of nanocrystals generated a photoelectric peak for Cs-137 gamma (662 keV) with 11.4% energy resolution. PMID:26478816

In vivo selective cancer-tracking gadolinium eradicator as new-generation photodynamic therapy agent

PubMed Central

Zhang, Tao; Lan, Rongfeng; Chan, Chi-Fai; Law, Ga-Lai; Wong, Wai-Kwok; Wong, Ka-Leung

2014-01-01

In this work, we demonstrate a modality of photodynamic therapy (PDT) through the design of our truly dual-functional—PDT and imaging—gadolinium complex (Gd-N), which can target cancer cells specifically. In the light of our design, the PDT drug can specifically localize on the anionic cell membrane of cancer cells in which its laser-excited photoemission signal can be monitored without triggering the phototoxic generation of reactive oxygen species—singlet oxygen—before due excitation. Comprehensive in vitro and in vivo studies had been conducted for the substantiation of the effectiveness of Gd-N as such a tumor-selective PDT photosensitizer. This treatment modality does initiate a new direction in the development of “precision medicine” in line with stem cell and gene therapies as tools in cancer therapy. PMID:25453097

Reticular Appearance on Gadolinium-enhanced T1- and Diffusion-weighted MRI, and Low Apparent Diffusion Coefficient Values in Microcystic Meningioma Cysts.

PubMed

Terada, Yukinori; Toda, Hiroki; Okumura, Ryosuke; Ikeda, Naokado; Yuba, Yoshiaki; Katayama, Toshiro; Iwasaki, Koichi

2018-03-01

Microcystic meningioma, a rare meningioma subtype, can present diagnostic difficulty. We aimed to investigate the historadiological properties of microcystic meningioma using conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) analysis. We retrospectively analyzed conventional MRI and DWI results of six microcystic meningioma cases by examining their appearance and determining their apparent diffusion coefficient (ADC) values. The ADC values of the intratumoral components were normalized with ADC values of the cerebrospinal fluid in the lateral ventricle (ADC ratios). As cystic formations are frequently associated with microcystic meningiomas, their MRI characteristics were compared with the imaging data from 11 cystic meningiomas of non-microcystic subtypes. We found that cysts in microcystic meningioma tended to have a reticular appearance on DWI, as they did on gadolinium-enhanced T1-weighted imaging. Additionally, these reticular cysts had significantly lower ADC ratios than microcystic non-reticular and non-microcystic cysts. These DWI characteristics likely reflect the histological properties of microcystic meningioma. A reticular appearance on gadolinium-enhanced T1-weighted MRI and DWI, and cyst formation with relatively low ADC values can be diagnostic markers of microcystic meningiomas.

Inhibition of selectin binding

DOEpatents

Nagy, Jon O.; Spevak, Wayne R.; Dasgupta, Falguni; Bertozzi, Caroline

2001-10-09

This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.

Inhibition of selectin binding

DOEpatents

Nagy, Jon O.; Spevak, Wayne R.; Dasgupta, Falguni; Bertozzi, Caroline

1999-01-01

This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.

Inhibition of selectin binding

DOEpatents

Nagy, Jon O.; Spevak, Wayne R.; Dasgupta, Falguni; Bertozzi, Carolyn

1999-10-05

This invention provides a system for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, this system can be used to palliate certain inflammatory and immunological conditions.

GADOLINIUM OXALATE SOLUBILITY MEASUREMENTS IN NITRIC ACID SOLUTIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pierce, R. A.

2012-03-12

HB-Line will begin processing Pu solutions during FY2012 that will involve the recovery of Pu using oxalate precipitation and filtration. After the precipitation and filtration processes, the filtrate solution will be transferred from HB-Line to H-Canyon. The presence of excess oxalate and unfiltered Pu oxalate solids in these solutions create a criticality safety issue if they are sent to H-Canyon without controls in H-Canyon. One approach involves H-Canyon receiving the filtrate solution into a tank that is poisoned with soluble gadolinium (Gd). Decomposition of the oxalate will occur within a subsequent H-Canyon vessel. The receipt of excess oxalate into themore » H-Canyon receipt tanks has the potential to precipitate a portion of the Gd poison in the receipt tanks. Because the amount of Gd in solution determines the maximum amount of Pu solids that H-Canyon can receive, H-Canyon Engineering requested that SRNL determine the solubility of Gd in aqueous solutions of 4-10 M nitric acid (HNO{sub 3}), 4-12 g/L Gd, and 0.15-0.25 M oxalic acid (H{sub 2}C{sub 2}O{sub 4}) at 25 °C. The target soluble Gd concentration is 6 g/L. The data indicate that the target can be achieved above 6 M HNO{sub 3} and below 0.25 M H{sub 2}C{sub 2}O{sub 4}. At 25 °C, for 6 M HNO{sub 3}, 11 g/L and 7 g/L Gd are soluble in 0.15 M and 0.25 M H{sub 2}C{sub 2}O{sub 4}, respectively. In 4 M HNO{sub 3}, the Gd solubility drops significantly to 2.5 g/L and 0.8 g/L in 0.15 M and 0.25 M H{sub 2}C{sub 2}O{sub 4}, respectively. The solubility of Gd at 8-10 M HNO{sub 3} exceeds the solubility at 6 M HNO{sub 3}. The data for 4 M HNO{sub 3} showed good agreement with data in the literature. To achieve a target of 6 g/L soluble Gd in solution in the presence of 0.15-0.25 M oxalate, the HNO{sub 3} concentration must be maintained at or above 6 M HNO{sub 3}. The solubility of Gd in 4 M HNO{sub 3} with 0.15 M oxalate at 10 °C is about 1.5 g/L. For 6 M HNO{sub 3} with 0.15 M oxalate, the solubility of

Terminal-group oxidation of retinol by mouse epidermis. Inhibition in vitro and in vivo.

PubMed Central

Connor, M J; Smit, M H

1987-01-01

Locally applied retinol is metabolized to retinoic acid in mouse epidermis in vivo. To characterize the oxidation system we investigated the ability of soluble extracts of hairless-mouse epidermis to convert retinol and retinal into retinoic acid. The extracts oxidized retinol to retinoic acid in two steps catalysed by two NAD+-dependent enzymes that were resolved on h.p.l.c. The first enzyme catalyses the reversible oxidation of retinol to retinal and is an alcohol dehydrogenase isoenzyme. The second enzyme oxidizes retinal to retinoic acid. Retinol oxidation by epidermal extracts was inhibited by the alcohol dehydrogenase inhibitor 4-methylpyrazole and by the polyene citral. The toxicity and relatively low potency at inhibiting the epidermal alcohol dehydrogenase isoenzyme curtailed the use of 4-methylpyrazole in vivo. However, citral significantly inhibited retinoic acid formation from retinol in the epidermis in vivo. The ability to inhibit the oxidation of retinol to retinoic acid in mouse epidermis provides a potential method to resolve the roles of retinol and retinoic acid in epithelial function. PMID:3663136

Association of left ventricular late gadolinium enhancement with left atrial low voltage areas in patients with atrial fibrillation.

PubMed

Stegmann, Clara; Jahnke, Cosima; Paetsch, Ingo; Hilbert, Sebastian; Arya, Arash; Bollmann, Andreas; Hindricks, Gerhard; Sommer, Philipp

2018-02-06

Presence of late gadolinium enhancement (LGE) is related to adverse cardiovascular outcome. Many patients suffering from atrial fibrillation (AF) undergo cardiovascular magnetic resonance (CMR) imaging prior to ablation. Since quantification of atrial fibrosis still lacks reproducibility, we sought to investigate risk factors for the presence of left ventricular (LV)-LGE and a possible correlation between ventricular fibrosis as defined by positive LGE and pathological atrial voltage maps evaluated by 3D mapping systems. Between May 2015 and January 2017, 241 patients with AF (73% persistent AF, 71% male, mean age 62.8 ± 10.1 years, Redo procedure in 24%, AF history 4.5 ± 5.2 years) underwent CMR including LV LGE prior to pulmonary vein (PV) isolation at Heart Center Leipzig. Depending on CMR results, two groups were separated: 'LV-LGE negative' (Group A, n = 197, 82%) and 'LV-LGE positive' (Group B, n = 44, 18%). To identify low voltage areas (LVA), a 3D electro-anatomic map was created during PV isolation. Multivariate analysis revealed male gender [odds ratio (OR) 7.6, 95% confidence interval (95% CI) 2.4-23.9, P = 0.001] and an increased CHA2DS2VASc Score (OR 1.6, 95% CI 1.2-2.2, P = 0.004) as significantly associated with LV-LGE. Impaired left ventricular ejection fraction, LV dilatation, larger LA size and, enlarged septum diameter occurred significantly more often in the 'LGE positive' group. Low voltage areas were detected in 83 patients overall (34%): Group A: n = 64/197 (33%), Group B: n = 19/44 (43%) (P = 0.177). Male gender and high CHA2DS2VASc Score are significantly associated with presence of LV-LGE, but LV-LGE is not associated with left atrial LVA. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.

Direct comparison of intra-articular versus intravenous delayed gadolinium-enhanced MRI of hip joint cartilage.

PubMed

Zilkens, Christoph; Miese, Falk; Kim, Young-Jo; Jäger, Marcus; Mamisch, Tallal C; Hosalkar, Harish; Antoch, Gerald; Krauspe, Rüdiger; Bittersohl, Bernd

2014-01-01

To investigate the potential of delayed gadolinium-enhanced magnetic resonance imaging in cartilage (dGEMRIC) after intra-articular (ia) contrast agent administration at 3 Tesla (T), a paired study comparing intravenous (iv) dGEMRIC (standard) with ia-dGEMRIC was performed. Thirty-five symptomatic patients with suspected cartilage damage underwent ia- and iv-dGEMRIC. MRI was performed with a 3T system wherein the interval between both measurements was 2 weeks. For iv-dGEMRIC, FDA approved Gd-DOTA(-) was injected intravenously 45 min before the MRI scan. For ia-dGEMRIC, 10-20 mL of a 2 mM solution of Gd- DOTA(-) was injected under fluoroscopic guidance 30 min before the MRI scan. Both ia- and iv-dGEMRIC demonstrated the typical T1Gd pattern in hip joint cartilage with increasing values toward the superior regions in acetabular cartilage reflecting the higher glycosaminoglycan (GAG) content in the main weight-bearing area. Correlation analysis revealed a moderate correlation between both techniques (r = 0.439, P-value < 0.001), whereas the T1Gd values for iv-dGEMRIC were significantly higher than those for ia-dGEMRIC. This corresponds with the Bland-Altman plot analysis, which revealed a systemic bias (higher T1Gd values after iv gadolinium application) of ∼70 ms. Ia-dGEMRIC was able to reveal the characteristic T1Gd pattern in hip joint cartilage confirming the sensitivity of ia-dGEMRIC for GAG. In addition, there was a significant correlation between iv-dGEMRIC and ia-dGEMRIC. However, the T1Gd values after ia contrast media application were significantly lower than those after iv application that has to be considered for future studies. Copyright © 2013 Wiley Periodicals, Inc.

Aqueous stability of gadolinium in surface waters receiving sewage treatment plant effluent, Boulder Creek, Colorado.

PubMed

Verplanck, Philip L; Taylor, Howard E; Nordstrom, D Kirk; Barber, Larry B

2005-09-15

In many surface waters, sewage treatment plant (STP) effluent is a substantial source of both regulated and unregulated contaminants, including a suite of complex organic compounds derived from household chemicals, pharmaceuticals, and industrial and medical byproducts. In addition, STP effluents in some urban areas have also been shown to have a positive gadolinium (Gd) anomaly in the rare earth element (REE) pattern, with the Gd derived from its use in medical facilities. REE concentrations are relatively easy to measure compared to many organic wastewater compounds and may provide a more widely utilized tracer of STP effluents. To evaluate whether sewage treatment plant-associated Gd is a useful tracer of treatment plant effluent, an investigation of the occurrence, fate, and transport of rare earth elements was undertaken. The rare earth element patterns of four of five STP effluents sampled display positive Gd anomalies. The one site that did not have a Gd anomaly serves a small community, population 1200, with no medical facilities. Biosolids from a large metropolitan STP are not enriched in Gd even though the effluent is, suggesting that a substantial fraction of Gd remains in the aqueous phase through routine treatment plant operation. To evaluate whether STP-derived Gd persists in the fluvial environment, a 14-km study reach downstream of an STP was sampled. Gadolinium anomalies were present at all five downstream sites, but the magnitude of the anomaly decreased. Effluent from STPs is a complex mixture of organic and inorganic constituents, and to better understand the chemical interactions and their effect on REEs, the aqueous speciation was modeled using comprehensive chemical analyses of water samples collected downstream of STP input. These calculations suggest that the REEs will likely remain dissolved because phosphate and carbonate complexes dominate over free REE ions. This study supports the application of Gd anomalies as a useful tracer of urban

Aqueous stability of gadolinium in surface waters receiving sewage treatment plant effluent Boulder Creek, Colorado

USGS Publications Warehouse

Verplanck, P.L.; Taylor, Howard E.; Nordstrom, D. Kirk; Barber, L.B.

2005-01-01

In many surface waters, sewage treatment plant (STP) effluent is a substantial source of both regulated and unregulated contaminants, including a suite of complex organic compounds derived from household chemicals, pharmaceutical, and industrial and medical byproducts. In addition, STP effluents in some urban areas have also been shown to have a positive gadolinium (Gd) anomaly in the rare earth element (REE) pattern, with the Gd derived from its use in medical facilities. REE concentrations are relatively easy to measure compared to many organic wastewater compounds and may provide a more widely utilized tracer of STP effluents. To evaluate whether sewage treatment plant-associated Gd is a useful tracer of treatment plant effluent, an investigation of the occurrence, fate, and transport of rare earth elements was undertaken. The rare earth element patterns of four of five STP effluents sampled display positive Gd anomalies. The one site that did not have a Gd anomaly serves a small community, population 1200, with no medical facilities. Biosolids from a large metropolitan STP are not enriched in Gd even though the effluent is, suggesting that a substantial fraction of Gd remains in the aqueous phase through routine treatment plant operation. To evaluate whether STP-derived Gd persists in the fluvial environment, a 14-km study reach downstream of an STP was sampled. Gadolinium anomalies were present at all five downstream sites, but the magnitude of the anomaly decreased. Effluent from STPs is a complex mixture of organic and inorganic constituents, and to better understand the chemical interactions and their effect on REEs, the aqueous speciation was modeled using comprehensive chemical analyses of water samples collected downstream of STP input. These calculations suggest that the REEs will likely remain dissolved because phosphate and carbonate complexes dominate over free REE ions. This study supports the application of Gd anomalies as a useful tracer of urban

Performance of Large Neutron Detectors Containing Lithium-Gadolinium-Borate Scintillator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slaughter, David M.; Stuart, Cory R.; Klaass, R. Fred

2015-07-01

This paper describes the development and testing of a neutron counter, spectrometer, and dosimeter that is compact, efficient, and accurate. A self-contained neutron detection instrument has wide applications in health physics, scientific research, and programs to detect, monitor, and control strategic nuclear materials (SNM). The 1.3 liter detector head for this instrument is a composite detector with an organic scintillator containing uniformly distributed {sup 6}Li{sub 6}{sup nat}Gd{sup 10}B{sub 3}O{sub 9}:Ce (LGB:Ce) microcrystals. The plastic scintillator acts to slow impinging neutrons and emits light proportional to the energy lost by the neutrons as they moderate in the detector body. Moderating neutronsmore » that have slowed sufficiently capture in one of the Lithium-6, Boron-10, or Gadolinium-157 atoms in the LGB:Ce scintillator, which then releases the capture energy in a characteristic cerium emission pulse. The measured captured pulses indicate the presence of neutrons. When a scintillating fluor is present in the plastic, the light pulse resulting from the neutron moderating in the plastic is paired with the LGB:Ce capture pulse to identify the energy of the neutron. About 2% of the impinging neutrons lose all of their energy in a single collision with the detector. There is a linear relationship between the pulse areas of this group of neutrons and energy. The other 98% of neutrons have a wide range of collision histories within the detector body. When these neutrons are 'binned' into energy groups, each group contains a distribution of pulse areas. This data was used to assist in the unfolding of the neutron spectra. The unfolded spectra were then validated with known spectra, at both neutron emitting isotopes and fission/accelerator facilities. Having validated spectra, the dose equivalent and dose rate are determined by applying standard, regulatory damage coefficients to the measured neutron counts for each energy bin of the spectra. Testing

Band-gap modulation via gallium substitution in cerium doped gadolinium aluminum garnet using a mixed fuel combustion approach

NASA Astrophysics Data System (ADS)

Tyagi, Mohit; Pitale, Shreyas S.; Ghosh, Manoranjan; Shinde, Seema

2014-04-01

Cerium doped Gadolinium garnets (Gd3AlxGa5-xO12 where 0≤x≤5) are synthesized via combustion synthesis using mixture of urea and glycine fuels. A 4h Post annealing at 1400 oC is found to be necessary for pure phase formation. Lattice spacing variation as a result of partial or total Ga substitution at Al site was mapped by X-ray diffraction. Photoluminescence emission of Ce shifts as a consequence of Ga substitution and therefore suggests a local re-adjustment of crystal field around activator site.

Inhibition of acetylcholinesterase by (1S,3S)-isomalathion proceeds with loss of thiomethyl: kinetic and mass spectral evidence for an unexpected primary leaving group.

PubMed

Doorn, J A; Gage, D A; Schall, M; Talley, T T; Thompson, C M; Richardson, R J

2000-12-01

Previous work demonstrated kinetically that inhibition of mammalian acetylcholinesterase (AChE) by (1S)-isomalathions may proceed by loss of thiomethyl instead of the expected diethyl thiosuccinate as the primary leaving group followed by one of four possible modes of rapid aging. This study sought to identify the adduct that renders AChE refractory toward reactivation after inhibition with the (1S, 3S)-stereoisomer. Electric eel acetylcholinesterase (EEAChE) was inhibited with the four stereoisomers of isomalathion, and rate constants for spontaneous and oxime-mediated reactivation (k(3)) were measured. Oxime-mediated k(3) values were >25-fold higher for enzyme inhibited by (1R)- versus (1S)-stereoisomers with the greatest contrast between the (1R,3R)- and (1S,3S)-enantiomers. EEAChE inactivated by (1R,3R)-isomalathion reactivated spontaneously and in the presence of pyridine-2-aldoxime methiodide (2-PAM) with k(3) values of 1.88 x 10(5) and 4.18 x 10(5) min(-)(1), respectively. In contrast, enzyme treated with the (1S,3S)-enantiomer had spontaneous and 2-PAM-mediated k(3) values of 0 and 6.05 x 10(3) min(-)(1), respectively. The kinetic data that were measured were consistent with those obtained for mammalian AChE used in previous studies. Identification of the adduct that renders EEAChE stable toward reactivation after inhibition with (1S,3S)-isomalathion was accomplished using a peptide mass mapping approach with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). A peak with a mass corresponding to the active site peptide containing the catalytic Ser with a covalently bound O-methyl phosphate adduct was found in the mass spectra of (1S, 3S)-treated EEAChE but not control samples. Identities of the modified active site peptide and adduct were confirmed by fragmentation in MALDI-TOF-MS post-source decay (PSD) analysis, and peaks corresponding to the loss of an adduct as phosphorous/phosphoric acid methyl ester were

Enhancements in hepatobiliary imaging: the spectrum of gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid usages in hepatobiliary magnetic resonance imaging.

PubMed

Channual, Stephanie; Pahwa, Anokh; Lu, David S; Raman, Steven S

2016-09-01

Gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a unique hepatocyte-specific contrast agent approved for clinical use in the United States in 2008. Gd-EOB-DTPA-enhanced MR has shown to improve detection and characterization of hepatic lesions. Gd-EOB-DTPA is now being routinely used in daily clinical practice worldwide. Therefore, it is important for radiologists to be familiar with the potential uses and pitfalls of Gd-EOB-DTPA, which extends beyond the assessment of focal hepatic lesions. The purpose of this article is to review the various usages of Gd-EOB-DTPA in hepatobiliary MR imaging.

Gadolinium and didymium (praseodymium/neodymium) cations as capture agents in lightmicroscopical histochemistry of acid and alkaline phosphatase.

PubMed

Halbhuber, K J; Zimmermann, N

1987-01-01

In previous papers, cerium and lanthanum based methods for light-microscopical detection of acid and alkaline phosphatase activity were proposed. In this paper, the usefulness of other lanthanide cations such as gadolinium and praseodymium/neodymium cations as capture agents in phosphatase histochemistry is tested. It is evident that phosphate ions were sufficiently trapped by these cations. According to the lead and silver multistep procedures earlier described it is possible to visualize alkaline phosphatase activity in the brush borders of the intestine or kidney as well as acid phosphatase activity in the lysosomes. These methods can be recommended.

Gadolinium-doped water cerenkov-based neutron and high energy gamma-ray detector and radiation portal monitoring system

DOEpatents

Dazeley, Steven A; Svoboda, Robert C; Bernstein, Adam; Bowden, Nathaniel

2013-02-12

A water Cerenkov-based neutron and high energy gamma ray detector and radiation portal monitoring system using water doped with a Gadolinium (Gd)-based compound as the Cerenkov radiator. An optically opaque enclosure is provided surrounding a detection chamber filled with the Cerenkov radiator, and photomultipliers are optically connected to the detect Cerenkov radiation generated by the Cerenkov radiator from incident high energy gamma rays or gamma rays induced by neutron capture on the Gd of incident neutrons from a fission source. The PMT signals are then used to determine time correlations indicative of neutron multiplicity events characteristic of a fission source.

Co-Precipitation Synthesis of Gadolinium Aluminum Gallium Oxide (GAGG) via Different Precipitants

NASA Astrophysics Data System (ADS)

Sun, Yan; Yang, Shenghui; Zhang, Ye; Jiang, Jun; Jiang, Haochuan

2014-02-01

In order to obtain a uniform transparent ceramic scintillator, well-dispersed fine starting powders with high-purity, small grain size, spherical morphology and high sinter-ability are necessary. In this study, Ce3+ doped gadolinium aluminum gallium garnet Gd3Al3Ga2O12 (GAGG) powders were synthesized by the co-precipitation method. NH4OH, NH4HCO3 and the mixed solution of NH4OH and NH4HCO3 were used as precipitants, respectively. The precursor composition, phase formation process, microstructure, morphology, particle size distribution and luminescent properties of obtained GAGG powders were measured. The results show that powders prepared using the mixed precipitant exhibit the best microstructural morphology, good sinter-ability and highest luminescent intensity. Pure GAGG polycrystalline powders could be obtained at about 950°C for 1.5 h and the average size of the particles is about 50 nm. The photoluminescence spectrum shows a strong green-yellow emission near 540 nm.

Polydisulfide Manganese(II) Complexes as Non-Gadolinium Biodegradable Macromolecular MRI Contrast Agents

PubMed Central

Ye, Zhen; Jeong, Eun-Kee; Wu, Xueming; Tan, Mingqian; Yin, Shouyu; Lu, Zheng-Rong

2011-01-01

Purpose To develop safe and effective manganese(II) based biodegradable macromolecular MRI contrast agents. Materials and Methods In this study, we synthesized and characterized two polydisulfide manganese(II) complexes, Mn-DTPA cystamine copolymers and Mn-EDTA cystamine copolymers, as new biodegradable macromolecular MRI contrast agents. The contrast enhancement of the two manganese based contrast agents were evaluated in mice bearing MDA-MB-231 human breast carcinoma xenografts, in comparison with MnCl2. Results The T1 and T2 relaxivities were 4.74 and 10.38 mM−1s−1 per manganese at 3T for Mn-DTPA cystamine copolymers (Mn=30.50 kDa) and 6.41 and 9.72 mM−1s−1 for Mn-EDTA cystamine copolymers (Mn= 61.80 kDa). Both polydisulfide Mn(II) complexes showed significant liver, myocardium and tumor enhancement. Conclusion The manganese based polydisulfide contrast agents have a potential to be developed as alternative non-gadolinium contrast agents for MR cancer and myocardium imaging. PMID:22031457

High-mobility group box 1 inhibits HCO3− absorption in medullary thick ascending limb through a basolateral receptor for advanced glycation end products pathway

PubMed Central

George, Thampi; Watts, Bruns A.

2015-01-01

High-mobility group box 1 (HMGB1) is a damage-associated molecule implicated in mediating kidney dysfunction in sepsis and sterile inflammatory disorders. HMGB1 is a nuclear protein released extracellularly in response to infection or injury, where it interacts with Toll-like receptor 4 (TLR4) and other receptors to mediate inflammation. Previously, we demonstrated that LPS inhibits HCO3- absorption in the medullary thick ascending limb (MTAL) through a basolateral TLR4-ERK pathway (Watts BA III, George T, Sherwood ER, Good DW. Am J Physiol Cell Physiol 301: C1296–C1306, 2011). Here, we examined whether HMGB1 could inhibit HCO3- absorption through the same pathway. Adding HMGB1 to the bath decreased HCO3− absorption by 24% in isolated, perfused rat and mouse MTALs. In contrast to LPS, inhibition by HMGB1 was preserved in MTALs from TLR4−/− mice and was unaffected by ERK inhibitors. Inhibition by HMGB1 was eliminated by the receptor for advanced glycation end products (RAGE) antagonist FPS-ZM1 and by neutralizing anti-RAGE antibody. Confocal immunofluorescence showed expression of RAGE in the basolateral membrane domain. Inhibition of HCO3−absorption by HMGB1 through RAGE was additive to inhibition by LPS through TLR4 and to inhibition by Gram-positive bacterial molecules through TLR2. Bath amiloride, which selectively prevents inhibition of MTAL HCO3− absorption mediated through Na+/H+ exchanger 1 (NHE1), eliminated inhibition by HMGB1. We conclude that HMGB1 inhibits MTAL HCO3− absorption through a RAGE-dependent pathway distinct from TLR4-mediated inhibition by LPS. These studies provide new evidence that HMGB1-RAGE signaling acts directly to impair the transport function of renal tubules. They reveal a novel paradigm for sepsis-induced renal tubule dysfunction, whereby exogenous pathogen-associated molecules and endogenous damage-associated molecules act directly and independently to inhibit MTAL HCO3− absorption through different receptor

Gadolinium sulfate modified by formate to obtain optimized magneto-caloric effect.

PubMed

Xu, Long-Yang; Zhao, Jiong-Peng; Liu, Ting; Liu, Fu-Chen

2015-06-01

Three new Gd(III) based coordination polymers [Gd2(C2H6SO)(SO4)3(H2O)2]n (1), {[Gd4(HCOO)2(SO4)5(H2O)6]·H2O}n (2), and [Gd(HCOO)(SO4)(H2O)]n (3) were obtained by modifying gadolinium sulfate. With the gradual increase of the volume ratio of HCOOH and DMSO in synthesis, the formate anions begin to coordinate with metal centers; this results in the coordination numbers of sulfate anion increasing and the contents of water and DMSO molecules decreasing in target complexes. Accordingly, spin densities both per mass and per volume were enhanced step by step, which are beneficial for the magneto-caloric effect (MCE). Magnetic studies reveal that with the more formate anions present, the larger the negative value of magnetic entropy change (-ΔSm) is. Complex 3 exhibits the largest -ΔSm = 49.91 J kg(-1) K(-1) (189.51 mJ cm(-3) K(-1)) for T = 2 K and ΔH = 7 T among three new complexes.

Acute Respiratory Distress Syndrome after the Use of Gadolinium Contrast Media.

PubMed

Park, Jihye; Byun, Il Hwan; Park, Kyung Hee; Lee, Jae-Hyun; Nam, Eun Ji; Park, Jung-Won

2015-07-01

Acute respiratory distress syndrome (ARDS) is a medical emergency that threatens life. To this day, ARDS is very rarely reported by iodine contrast media, and there is no reported case of ARDS induced by gadolinium contrast media. Here, we present a case with ARDS after the use of gadobutrol (Gadovist) as a magnetic resonance imaging (MRI) contrast medium. A 26 years old female without any medical history, including allergic diseases and without current use of drugs, visited the emergency room for abdominal pain. Her abdominopelvic computed tomography with iodine contrast media showed a right ovarian cyst and possible infective colitis. Eighty-three hours later, she underwent pelvis MRI after injection of 7.5 mL (0.1 mL/kg body weight) of gadobutrol (Gadovist) to evaluate the ovarian cyst. She soon presented respiratory difficulty, edema of the lips, nausea, and vomiting, and we could hear wheezing upon auscultation. She was treated with dexamethasone, epinephrine, and norepinephrine. Her chest X-ray showed bilateral central bat-wing consolidative appearance. Managed with mechanical ventilation, she was extubated 3 days later and discharged without complications.

Task Inhibition and Response Inhibition in Older vs. Younger Adults: A Diffusion Model Analysis

PubMed Central

Schuch, Stefanie

2016-01-01

Differences in inhibitory ability between older (64–79 years, N = 24) and younger adults (18–26 years, N = 24) were investigated using a diffusion model analysis. Participants performed a task-switching paradigm that allows assessing n−2 task repetition costs, reflecting inhibitory control on the level of tasks, as well as n−1 response-repetition costs, reflecting inhibitory control on the level of responses. N−2 task repetition costs were of similar size in both age groups. Diffusion model analysis revealed that for both younger and older adults, drift rate parameters were smaller in the inhibition condition relative to the control condition, consistent with the idea that persisting task inhibition slows down response selection. Moreover, there was preliminary evidence for task inhibition effects in threshold separation and non-decision time in the older, but not the younger adults, suggesting that older adults might apply different strategies when dealing with persisting task inhibition. N−1 response-repetition costs in mean RT were larger in older than younger adults, but in mean error rates tended to be larger in younger than older adults. Diffusion-model analysis revealed longer non-decision times in response repetitions than response switches in both age groups, consistent with the idea that motor processes take longer in response repetitions than response switches due to persisting response inhibition of a previously executed response. The data also revealed age-related differences in overall performance: Older adults responded more slowly and more accurately than young adults, which was reflected by a higher threshold separation parameter in diffusion model analysis. Moreover, older adults showed larger non-decision times and higher variability in non-decision time than young adults, possibly reflecting slower and more variable motor processes. In contrast, overall drift rate did not differ between older and younger adults. Taken together

Effect of Renal Function on Gadolinium-Related Signal Increases on Unenhanced T1-Weighted Brain Magnetic Resonance Imaging.

PubMed

Cao, Yan; Zhang, Yang; Shih, George; Zhang, Yan; Bohmart, Andrew; Hecht, Elizabeth M; Prince, Martin R

2016-11-01

The purpose of this study was to determine if renal function affects signal changes in the deep brain nuclei on unenhanced T1-weighted images after administration of linear gadolinium-based contrast agents (GBCAs). An electronic medical records search of 2 large medical centers identified 25 patients who received linear GBCA while on hemodialysis and had unenhanced T1-weighted images of the brain before and after. The dentate-to-cerebellar peduncle (DCP) ratio, globus pallidus-to-mid thalamus (GPT) ratio, and choroid plexus-to-nearby white matter ratio were measured and compared with 25 age/sex/GBCA exposure-matched control patients with normal or near-normal renal function (estimated glomerular filtration rate >60 mL/min per 1.73 m). Two additional control groups included 13 patients on hemodialysis without GBCA exposure and 13 age/sex-matched patients with estimated glomerular filtration rate greater than 60 mL/min per 1.73 m. Hemodialysis patients (n = 25) with an average of 1.8 linear GBCA administrations had a 4.9% mean increase (1.00 ± 0.04 vs 1.05 ± 0.05; P < 0.001) in DCP, which was greater than the 1.6% change (0.99 ± 0.04 vs 1.00 ± 0.05; P = 0.08) observed in matched controls (P = 0.01). There was no significant signal change in the DCP ratio in the 13 hemodialysis patients (0.99 ± 0.04 vs 0.99 ± 0.04; P = 0.78) and 13 age/sex-matched patients (0.99 ± 0.02 vs 0.99 ± 0.03; P = 0.78) who did not receive GBCA. The hemodialysis patients had a baseline GPT that was higher than nondialysis patients (P < 0.001). However, the GPT change after GBCA administration was not significantly different from controls. Increased signal in the choroid plexus on unenhanced T1-weighted images after GBCA administration was noted in hemodialysis patients (0.72 ± 0.20 vs 0.86 ± 0.23; P = 0.006); however, a multivariate analysis showed this to be primarily related to hemodialysis (P = 0.003) with only a trend toward relating to GBCA exposure (P = 0.07). Hemodialysis

Pineapple juice and its fractions in enzymatic browning inhibition of banana [Musa (AAA group) Gros Michel].

PubMed

Chaisakdanugull, Chitsuda; Theerakulkait, Chockchai; Wrolstad, Ronald E

2007-05-16

The effectiveness of pineapple juice in enzymatic browning inhibition was evaluated on the cut surface of banana slices. After storage of banana slices at 15 degrees C for 3 days, pineapple juice showed browning inhibition to a similar extent as 8 mM ascorbic acid but less than 4 mM sodium metabisulfite. Fractionation of pineapple juice by a solid-phase C18 cartridge revealed that the directly eluted fraction (DE fraction) inhibited banana polyphenol oxidase (PPO) about 100% when compared to the control. The DE fraction also showed more inhibitory effect than 8 mM ascorbic acid in enzymatic browning inhibition of banana puree during storage at 5 degrees C for 24 h. Further identification of the DE fraction by fractionation with ion exchange chromatography and confirmation using model systems indicated that malic acid and citric acid play an important role in the enzymatic browning inhibition of banana PPO.

Should we stop thinking about inhibition? Searching for individual and age differences in inhibition ability.

PubMed

Rey-Mermet, Alodie; Gade, Miriam; Oberauer, Klaus

2018-04-01

Inhibition is often conceptualized as a unitary construct reflecting the ability to ignore and suppress irrelevant information. At the same time, it has been subdivided into inhibition of prepotent responses (i.e., the ability to stop dominant responses) and resistance to distracter interference (i.e., the ability to ignore distracting information). The present study investigated the unity and diversity of inhibition as a psychometric construct, and tested the hypothesis of an inhibition deficit in older age. We measured inhibition in young and old adults with 11 established laboratory tasks: antisaccade, stop-signal, color Stroop, number Stroop, arrow flanker, letter flanker, Simon, global-local, positive and negative compatibility tasks, and n-2 repetition costs in task switching. In both age groups, the inhibition measures from individual tasks had good reliabilities, but correlated only weakly among each other. Structural equation modeling identified a 2-factor model with factors for inhibition of prepotent responses and resistance to distracter interference. Older adults scored worse in the inhibition of prepotent response, but better in the resistance to distracter interference. However, the model had low explanatory power. Together, these findings call into question inhibition as a psychometric construct and the hypothesis of an inhibition deficit in older age. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Biodegradable gadolinium-chelated cationic poly(urethane amide) copolymers for gene transfection and magnetic resonance imaging.

PubMed

Gao, Xiaolong; Wang, Gangmin; Shi, Ting; Shao, Zhihong; Zhao, Peng; Shi, Donglu; Ren, Jie; Lin, Chao; Wang, Peijun

2016-08-01

Theranostic nano-polyplexes containing gene and imaging agents hold a great promise for tumor diagnosis and therapy. In this work, we develop a group of new gadolinium (Gd)-chelated cationic poly(urethane amide)s for gene delivery and T1-weighted magnetic resonance (MR) imaging. Cationic poly(urethane amide)s (denoted as CPUAs) having multiple disulfide bonds, urethane and amide linkages were synthesized by stepwise polycondensation reaction between 1,4-bis(3-aminopropyl)piperazine and a mixture of di(4-nitrophenyl)-2, 2'-dithiodiethanocarbonate (DTDE-PNC) and diethylenetriaminepentaacetic acid (DTPA) dianhydride at varied molar ratios. Then, Gd-chelated CPUAs (denoted as GdCPUAs) were produced by chelating Gd(III) ions with DTPA residues of CPUAs. These GdCPUAs could condense gene into nanosized and positively-charged polyplexes in a physiological condition and, however, liberated gene in an intracellular reductive environment. In vitro transfection experiments revealed that the GdCPUA at a DTDE-PNC/DTPA residue molar ratio of 85/15 induced the highest transfection efficiency in different cancer cells. This efficiency was higher than that yielded with 25kDa branched polyethylenimine as a positive control. GdCPUAs and their polyplexes exhibited low cytotoxicity when an optimal transfection activity was detected. Moreover, GdCPUAs may serve as contrast agents for T1-weighted magnetic resonance imaging. The results of this work indicate that biodegradable Gd-chelated cationic poly(urethane amide) copolymers have high potential for tumor theranostics. Copyright © 2016 Elsevier B.V. All rights reserved.

Scolopendra subspinipes mutilans protected the cerulein-induced acute pancreatitis by inhibiting high-mobility group box protein-1.

PubMed

Jo, Il-Joo; Bae, Gi-Sang; Park, Kyoung-Chel; Choi, Sun Bok; Jung, Won-Seok; Jung, Su-Young; Cho, Jung-Hee; Choi, Mee-Ok; Song, Ho-Joon; Park, Sung-Joo

2013-03-14

To evaluate the inhibitory effects of Scolopendra subspinipes mutilans (SSM) on cerulein-induced acute pancreatitis (AP) in a mouse model. SSM water extract (0.1, 0.5, or 1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein. Once AP developed, the stable cholecystokinin analogue, cerulein was injected hourly, over a 6 h period. Blood samples were taken 6 h later to determine serum amylase, lipase, and cytokine levels. The pancreas and lungs were rapidly removed for morphological examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. To specify the role of SSM in pancreatitis, the pancreatic acinar cells were isolated using collagenase method. Then the cells were pre-treated with SSM, then stimulated with cerulein. The cell viability, cytokine productions and high-mobility group box protein-1 (HMGB-1) were measured. Furthermore, the regulating mechanisms of SSM action were evaluated. The administration of SSM significantly attenuated the severity of pancreatitis and pancreatitis associated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization and necrosis. SSM treatment also reduced pancreatic weight/body weight ratio, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as tumor necrosis factor-α and interleukin-1β. In addition, treatment with SSM inhibited HMGB-1 expression in the pancreas during AP. In accordance with in vivo data, SSM inhibited the cerulein-induced acinar cell death, cytokine, and HMGB-1 release. SSM also inhibited the activation of c-Jun NH2-terminal kinase, p38 and nuclear factor (NF)-κB. These results suggest that SSM plays a protective role during the development of AP and pancreatitis associated lung injury via deactivating c-Jun NH2-terminal kinase, p38 and NF-κB.

Scolopendra subspinipes mutilans protected the cerulein-induced acute pancreatitis by inhibiting high-mobility group box protein-1

PubMed Central

Jo, Il-Joo; Bae, Gi-Sang; Park, Kyoung-Chel; Choi, Sun Bok; Jung, Won-Seok; Jung, Su-Young; Cho, Jung-Hee; Choi, Mee-Ok; Song, Ho-Joon; Park, Sung-Joo

2013-01-01

AIM: To evaluate the inhibitory effects of Scolopendra subspinipes mutilans (SSM) on cerulein-induced acute pancreatitis (AP) in a mouse model. METHODS: SSM water extract (0.1, 0.5, or 1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein. Once AP developed, the stable cholecystokinin analogue, cerulein was injected hourly, over a 6 h period. Blood samples were taken 6 h later to determine serum amylase, lipase, and cytokine levels. The pancreas and lungs were rapidly removed for morphological examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. To specify the role of SSM in pancreatitis, the pancreatic acinar cells were isolated using collagenase method. Then the cells were pre-treated with SSM, then stimulated with cerulein. The cell viability, cytokine productions and high-mobility group box protein-1 (HMGB-1) were measured. Furthermore, the regulating mechanisms of SSM action were evaluated. RESULTS: The administration of SSM significantly attenuated the severity of pancreatitis and pancreatitis associated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization and necrosis. SSM treatment also reduced pancreatic weight/body weight ratio, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as tumor necrosis factor-α and interleukin-1β. In addition, treatment with SSM inhibited HMGB-1 expression in the pancreas during AP. In accordance with in vivo data, SSM inhibited the cerulein-induced acinar cell death, cytokine, and HMGB-1 release. SSM also inhibited the activation of c-Jun NH2-terminal kinase, p38 and nuclear factor (NF)-κB. CONCLUSION: These results suggest that SSM plays a protective role during the development of AP and pancreatitis associated lung injury via deactivating c-Jun NH2-terminal kinase, p38 and NF-κB. PMID:23539679

Histology and Gadolinium Distribution in the Rodent Brain After the Administration of Cumulative High Doses of Linear and Macrocyclic Gadolinium-Based Contrast Agents.

PubMed

Lohrke, Jessica; Frisk, Anna-Lena; Frenzel, Thomas; Schöckel, Laura; Rosenbruch, Martin; Jost, Gregor; Lenhard, Diana Constanze; Sieber, Martin A; Nischwitz, Volker; Küppers, Astrid; Pietsch, Hubertus

2017-06-01

Retrospective studies in patients with primary brain tumors or other central nervous system pathologies as well as postmortem studies have suggested that gadolinium (Gd) deposition occurs in the dentate nucleus (DN) and globus pallidus (GP) after multiple administrations of primarily linear Gd-based contrast agents (GBCAs). However, this deposition has not been associated with any adverse effects or histopathological alterations. The aim of this preclinical study was to systematically examine differences between linear and macrocyclic GBCAs in their potential to induce changes in brain and skin histology including Gd distribution in high spatial resolution. Fifty male Wistar-Han rats were randomly allocated into control (saline, n = 10 rats) and 4 GBCA groups (linear GBCAs: gadodiamide and gadopentetate dimeglumine, macrocyclic GBCAs: gadobutrol and gadoteridol; n = 10 rats per group). The animals received 20 daily intravenous injections at a dose of 2.5 mmol Gd/kg body weight. Eight weeks after the last GBCA administration, the animals were killed, and the brain and skin samples were histopathologically assessed (hematoxylin and eosin; cresyl violet [Nissl]) and by immunohistochemistry. The Gd concentration in the skin, bone, brain, and skeletal muscle samples were analyzed using inductively coupled plasma mass spectroscopy (ICP-MS, n = 4). The spatial Gd distribution in the brain and skin samples was analyzed in cryosections using laser ablation coupled with ICP-MS (LA-ICP-MS, n = 3). For the ultra-high resolution of Gd distribution, brain sections of rats injected with gadodiamide or saline (n = 1) were assessed by scanning electron microscopy coupled to energy dispersive x-ray spectroscopy and transmission electron microscopy, respectively. No histological changes were observed in the brain. In contrast, 4 of 10 animals in the gadodiamide group but none of the animals in other groups showed macroscopic and histological nephrogenic systemic fibrosis-like skin

Controlled intracellular self-assembly of gadolinium nanoparticles as smart molecular MR contrast agents.

PubMed

Cao, Chun-Yan; Shen, Ying-Ying; Wang, Jian-Dong; Li, Li; Liang, Gao-Lin

2013-01-01

Herein we developed a new "smart" Gd-based MR contrast agent (i.e., 1) which is susceptive to furin, a protease overexpressed in tumor. Under the action of furin, 1 condenses to form dimers (1-Ds) and the latter self-assemble into gadolinium nanparticles (Gd-NPs). Relaxivity of 1-D is more than 2 folds of those of 1 and magnevist at 1.5 T, and 1.4 folds of that of 1 at 3 T. Intracellular condensation of 1 in furin-overexpressed MDA-MB-468 cells was proven with direct two-photon laser microscopy (TPLM) fluorescence imaging of the cells incubated with the europium analog of 1 (i.e., 2). Intracellular Gd-NPs of 1 were uncovered and characterized for the first time. MRI of MDA-MB-468 tumors showed that 1 has enhanced MR contrast within the tumors than that of its scrambled control 1-Scr.

Diuretic-enhanced gadolinium excretory MR urography: comparison of conventional gradient-echo sequences and echo-planar imaging.

PubMed

Nolte-Ernsting, C C; Tacke, J; Adam, G B; Haage, P; Jung, P; Jakse, G; Günther, R W

2001-01-01

The aim of this study was to investigate the utility of different gadolinium-enhanced T1-weighted gradient-echo techniques in excretory MR urography. In 74 urologic patients, excretory MR urography was performed using various T1-weighted gradient-echo (GRE) sequences after injection of gadolinium-DTPA and low-dose furosemide. The examinations included conventional GRE sequences and echo-planar imaging (GRE EPI), both obtained with 3D data sets and 2D projection images. Breath-hold acquisition was used primarily. In 20 of 74 examinations, we compared breath-hold imaging with respiratory gating. Breath-hold imaging was significantly superior to respiratory gating for the visualization of pelvicaliceal systems, but not for the ureters. Complete MR urograms were obtained within 14-20 s using 3D GRE EPI sequences and in 20-30 s with conventional 3D GRE sequences. Ghost artefacts caused by ureteral peristalsis often occurred with conventional 3D GRE imaging and were almost completely suppressed in EPI sequences (p < 0.0001). Susceptibility effects were more pronounced on GRE EPI MR urograms and calculi measured 0.8-21.7% greater in diameter compared with conventional GRE sequences. Increased spatial resolution degraded the image quality only in GRE-EPI urograms. In projection MR urography, the entire pelvicaliceal system was imaged by acquisition of a fast single-slice sequence and the conventional 2D GRE technique provided superior morphological accuracy than 2D GRE EPI projection images (p < 0.0003). Fast 3D GRE EPI sequences improve the clinical practicability of excretory MR urography especially in old or critically ill patients unable to suspend breathing for more than 20 s. Conventional GRE sequences are superior to EPI in high-resolution detail MR urograms and in projection imaging.

Clinical, biological, and skin histopathologic effects of ionic macrocyclic and nonionic linear gadolinium chelates in a rat model of nephrogenic systemic fibrosis.

PubMed

Fretellier, Nathalie; Idée, Jean-Marc; Guerret, Sylviane; Hollenbeck, Claire; Hartmann, Daniel; González, Walter; Robic, Caroline; Port, Marc; Corot, Claire

2011-02-01

the purpose of this study was to compare the clinical, pathologic, and biochemical effects of repeated administrations of ionic macrocyclic or nonionic linear gadolinium chelates (GC) in rats with impaired renal function. rats submitted to subtotal nephrectomy were allocated to single injections of 2.5 mmol/kg of gadodiamide (nonionic linear chelate), nonformulated gadodiamide (ie, without the free ligand caldiamide), gadoterate (ionic macrocyclic chelate), or saline for 5 consecutive days. Blinded semi-quantitative histopathologic and immunohistochemical examinations of the skin were performed, as well as clinical, hematological, and biochemical follow-up. Rats were killed at day 11. Long-term (up to day 32) follow-up of rats was also performed in an auxiliary study. epidermal lesions (ulcerations and scabs) were found in 4 of the 10 rats treated with nonformulated gadodiamide. Two rats survived the study period. Inflammatory signs were observed in this group. No clinical, hematological, or biochemical signs were observed in the saline and gadoterate- or gadodiamide-treated groups. Plasma fibroblast growth factor-23 levels were significantly higher in the gadodiamide group than in the gadoterate group (day 11). Decreased plasma transferrin-bound iron levels were measured in the nonformulated gadodiamide group. Histologic lesions were in the range: nonformulated gadodiamide (superficial epidermal lesions, inflammation, necrosis, and increased cellularity in papillary dermis) > gadodiamide (small superficial epidermal lesions and signs of degradation of collagen fibers in the dermis) > gadoterate (very few pathologic lesions, similar to control rats). repeated administration of the nonionic linear GC gadodiamide to renally impaired rats is associated with more severe histologic lesions and higher FGF-23 plasma levels than the macrocyclic GC gadoterate.

Anti-EpCAM scFv gadolinium chelate: a novel targeted MRI contrast agent for imaging of colorectal cancer.

PubMed

Khantasup, Kannika; Saiviroonporn, Pairash; Jarussophon, Suwatchai; Chantima, Warangkana; Dharakul, Tararaj

2018-05-08

The development of targeted contrast agents for magnetic resonance imaging (MRI) facilitates enhanced cancer imaging and more accurate diagnosis. In the present study, a novel contrast agent was developed by conjugating anti-EpCAM humanized scFv with gadolinium chelate to achieve target specificity. The material design strategy involved site-specific conjugation of the chelating agent to scFv. The scFv monomer was linked to maleimide-DTPA via unpaired cysteine at the scFv C-terminus, followed by chelation with gadolinium (Gd). Successful scFv-DTPA conjugation was achieved at 1:10 molar ratio of scFv to maleimide-DTPA at pH 6.5. The developed anti-EpCAM-Gd-DTPA MRI contrast agent was evaluated for cell targeting ability, in vitro serum stability, cell cytotoxicity, relaxivity, and MR contrast enhancement. A high level of targeting efficacy of anti-EpCAM-Gd-DTPA to an EpCAM-overexpressing HT29 colorectal cell was demonstrated by confocal microscopy. Good stability of the contrast agent was obtained and no cytotoxicity was observed in HT29 cells after 48 h incubation with 25-100 µM of Gd. Favorable imaging was obtained using anti-EpCAM-Gd-DTPA, including 1.8-fold enhanced relaxivity compared with Gd-DTPA, and MR contrast enhancement observed after binding to HT29. The potential benefit of this contrast agent for in vivo MR imaging of colorectal cancer, as well as other EpCAM positive cancers, is suggested and warrants further investigation.

Quantification and Assessment of the Chemical Form of Residual Gadolinium in the Brain After Repeated Administration of Gadolinium-Based Contrast Agents: Comparative Study in Rats.

PubMed

Frenzel, Thomas; Apte, Chirag; Jost, Gregor; Schöckel, Laura; Lohrke, Jessica; Pietsch, Hubertus

2017-07-01

Multiple clinical and preclinical studies have reported a signal intensity increase and the presence of gadolinium (Gd) in the brain after repeated administration of Gd-based contrast agents (GBCAs). This bioanalytical study in rat brain tissue was initiated to investigate whether the residual Gd is present as intact GBCA or in other chemical forms by using tissue fractionation and chromatography. Rats were divided randomly in 6 groups of 10 animals each. They received 10 daily injections of 2.5 mmol/kg bodyweight of 1 of 5 different GBCAs: linear GBCAs such as gadodiamide (Omniscan; GE Healthcare), gadopentetate dimeglumine (Gd-DTPA, Magnevist; Bayer), or gadobenate dimeglumine (Multihance; Bracco) and macrocyclic GBCAs such as gadobutrol (Gadovist; Bayer) and gadoterate meglumine (Gd-DOTA, Dotarem; Guerbet) or saline. On days 3 and 24 after the last injection (p.i.), 5 randomly chosen animals of each group were killed by exsanguination, and their brains were excised and divided into cerebrum, pons, and cerebellum. The brain sections were homogenized by sonication in ice-cold buffer at pH 7.4. Soluble and insoluble fractions were separated by centrifugation, and the soluble fractions were further separated by gel permeation chromatography (GPC). The Gd concentration in all tissue fractions and in the GPC eluate was measured by inductively coupled plasma-mass spectrometry. In a recovery control experiment, all GBCAs were spiked to blank brain tissue and more than 94% recovery of Gd in the tissue fractions was demonstrated. Only traces of the administered Gd were found in the rat brain tissue on day 3 and day 24 p.i. In the animals treated with macrocyclic GBCAs, Gd was found only in the soluble brain fraction and was present solely as low molecular weight molecules, most likely the intact GBCA. In the animals treated with linear GBCAs Gd was found to a large extent in the insoluble tissue fraction. The Gd concentration in the soluble fraction was comparable to the

Highly transparent cerium doped gadolinium gallium aluminum garnet ceramic prepared with precursors fabricated by ultrasonic enhanced chemical co-precipitation.

PubMed

Zhang, Ji-Yun; Luo, Zhao-Hua; Jiang, Hao-Chuan; Jiang, Jun; Chen, Chun-Hua; Zhang, Jing-Xian; Gui, Zhen-Zhen; Xiao, Na

2017-11-01

Cerium doped gadolinium gallium aluminum garnet (GGAG:Ce) ceramic precursors have been synthesized with an ultrasonic chemical co-precipitation method (UCC) and for comparison with a traditional chemical co-precipitation method (TCC). The effect of ultra-sonication on the morphology of powders and the transmittance of GGAG:Ce ceramics are studied. The results indicate that the UCC method can effectively improve the homogenization and sinterability of GGAG:Ce powders, which contribute to obtain high transparent GGAG ceramic with the highest transmittance of 81%. Copyright © 2017 Elsevier B.V. All rights reserved.

A smart T(1)-weighted MRI contrast agent for uranyl cations based on a DNAzyme-gadolinium conjugate.

PubMed

Xu, Weichen; Xing, Hang; Lu, Yi

2013-11-07

Rational design of smart MRI contrast agents with high specificity for metal ions remains a challenge. Here, we report a general strategy for the design of smart MRI contrast agents for detecting metal ions based on conjugation of a DNAzyme with a gadolinium complex. The 39E DNAzyme, which has high selectivity for UO2(2+), was conjugated to Gd(III)-DOTA and streptavidin. The binding of UO2(2+) to its 39E DNAzyme resulted in the dissociation of Gd(III)-DOTA from the large streptavidin, leading to a decrease of the T1 correlation time, and a change in the MRI signal.

Structural and functional bases of inhibited temperament.

PubMed

Clauss, Jacqueline A; Seay, April L; VanDerKlok, Ross M; Avery, Suzanne N; Cao, Aize; Cowan, Ronald L; Benningfield, Margaret M; Blackford, Jennifer Urbano

2014-12-01

Children born with an inhibited temperament are at heightened risk for developing anxiety, depression and substance use. Inhibited temperament is believed to have a biological basis; however, little is known about the structural brain basis of this vulnerability trait. Structural MRI scans were obtained from 84 (44 inhibited, 40 uninhibited) young adults. Given previous findings of amygdala hyperactivity in inhibited individuals, groups were compared on three measures of amygdala structure. To identify novel substrates of inhibited temperament, a whole brain analysis was performed. Functional activation and connectivity were examined across both groups. Inhibited adults had larger amygdala and caudate volume and larger volume predicted greater activation to neutral faces. In addition, larger amygdala volume predicted greater connectivity with subcortical and higher order visual structures. Larger caudate volume predicted greater connectivity with the basal ganglia, and less connectivity with primary visual and auditory cortex. We propose that larger volume in these salience detection regions may result in increased activation and enhanced connectivity in response to social stimuli. Given the strong link between inhibited temperament and risk for psychiatric illness, novel therapeutics that target these brain regions and related neural circuits have the potential to reduce rates of illness in vulnerable individuals. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Crystal structures of human group-VIIA phospholipase A2 inhibited by organophosphorus nerve agents exhibit non-aged complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samanta, Uttamkumar; Kirby, Stephen D.; Srinivasan, Prabhavathi

The enzyme group-VIIA phospholipase A2 (gVIIA-PLA2) is bound to lipoproteins in human blood and hydrolyzes the ester bond at the sn-2 position of phospholipid substrates with a short sn-2 chain. The enzyme belongs to a serine hydrolase superfamily of enzymes, which react with organophosphorus (OP) nerve agents. OPs ultimately exert their toxicity by inhibiting human acetycholinesterase at nerve synapses, but may additionally have detrimental effects through inhibition of other serine hydrolases. We have solved the crystal structures of gVIIA-PLA2 following inhibition with the OPs diisopropylfluorophosphate, sarin, soman and tabun. The sarin and soman complexes displayed a racemic mix of P{submore » R} and P{sub S} stereoisomers at the P-chiral center. The tabun complex displayed only the P{sub R} stereoisomer in the crystal. In all cases, the crystal structures contained intact OP adducts that had not aged. Aging refers to a secondary process OP complexes can go through, which dealkylates the nerve agent adduct and results in a form that is highly resistant to either spontaneous or oxime-mediated reactivation. Non-aged OP complexes of the enzyme were corroborated by trypsin digest and matrix-assisted laser desorption ionization mass spectrometry of OP-enzyme complexes. The lack of stereoselectivity of sarin reaction was confirmed by gas chromatography/mass spectrometry using a chiral column to separate and quantitate the unbound stereoisomers of sarin following incubation with enzyme. The structural details and characterization of nascent reactivity of several toxic nerve agents is discussed with a long-term goal of developing gVIIA-PLA2 as a catalytic bioscavenger of OP nerve agents.« less

Crystal structures of human group-VIIA phospholipase A2 inhibited by organophosphorus nerve agents exhibit non-aged complexes.

PubMed

Samanta, Uttamkumar; Kirby, Stephen D; Srinivasan, Prabhavathi; Cerasoli, Douglas M; Bahnson, Brian J

2009-08-15

The enzyme group-VIIA phospholipase A2 (gVIIA-PLA2) is bound to lipoproteins in human blood and hydrolyzes the ester bond at the sn-2 position of phospholipid substrates with a short sn-2 chain. The enzyme belongs to a serine hydrolase superfamily of enzymes, which react with organophosphorus (OP) nerve agents. OPs ultimately exert their toxicity by inhibiting human acetycholinesterase at nerve synapses, but may additionally have detrimental effects through inhibition of other serine hydrolases. We have solved the crystal structures of gVIIA-PLA2 following inhibition with the OPs diisopropylfluorophosphate, sarin, soman and tabun. The sarin and soman complexes displayed a racemic mix of P(R) and P(S) stereoisomers at the P-chiral center. The tabun complex displayed only the P(R) stereoisomer in the crystal. In all cases, the crystal structures contained intact OP adducts that had not aged. Aging refers to a secondary process OP complexes can go through, which dealkylates the nerve agent adduct and results in a form that is highly resistant to either spontaneous or oxime-mediated reactivation. Non-aged OP complexes of the enzyme were corroborated by trypsin digest and matrix-assisted laser desorption ionization mass spectrometry of OP-enzyme complexes. The lack of stereoselectivity of sarin reaction was confirmed by gas chromatography/mass spectrometry using a chiral column to separate and quantitate the unbound stereoisomers of sarin following incubation with enzyme. The structural details and characterization of nascent reactivity of several toxic nerve agents is discussed with a long-term goal of developing gVIIA-PLA2 as a catalytic bioscavenger of OP nerve agents.

MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain.

PubMed

Eide, Per Kristian; Ringstad, Geir

2015-11-01

Recently, the "glymphatic system" of the brain has been discovered in rodents, which is a paravascular, transparenchymal route for clearance of excess brain metabolites and distribution of compounds in the cerebrospinal fluid. It has already been demonstrated that intrathecally administered gadolinium (Gd) contrast medium distributes along this route in rats, but so far not in humans. A 27-year-old woman underwent magnetic resonance imaging (MRI) with intrathecal administration of gadobutrol, which distributed throughout her entire brain after 1 and 4.5 h. MRI with intrathecal Gd may become a tool to study glymphatic function in the human brain.

MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain

PubMed Central

Ringstad, Geir

2015-01-01

Recently, the “glymphatic system” of the brain has been discovered in rodents, which is a paravascular, transparenchymal route for clearance of excess brain metabolites and distribution of compounds in the cerebrospinal fluid. It has already been demonstrated that intrathecally administered gadolinium (Gd) contrast medium distributes along this route in rats, but so far not in humans. A 27-year-old woman underwent magnetic resonance imaging (MRI) with intrathecal administration of gadobutrol, which distributed throughout her entire brain after 1 and 4.5 h. MRI with intrathecal Gd may become a tool to study glymphatic function in the human brain. PMID:26634147

Band-gap modulation via gallium substitution in cerium doped gadolinium aluminum garnet using a mixed fuel combustion approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tyagi, Mohit; Pitale, Shreyas S.; Ghosh, Manoranjan

2014-04-24

Cerium doped Gadolinium garnets (Gd{sub 3}Al{sub x}Ga{sub 5−x}O{sub 12} where 0≤x≤5) are synthesized via combustion synthesis using mixture of urea and glycine fuels. A 4h Post annealing at 1400 oC is found to be necessary for pure phase formation. Lattice spacing variation as a result of partial or total Ga substitution at Al site was mapped by X-ray diffraction. Photoluminescence emission of Ce shifts as a consequence of Ga substitution and therefore suggests a local re-adjustment of crystal field around activator site.

Thermal neutron detector based on COTS CMOS imagers and a conversion layer containing Gadolinium

NASA Astrophysics Data System (ADS)

Pérez, Martín; Blostein, Juan Jerónimo; Bessia, Fabricio Alcalde; Tartaglione, Aureliano; Sidelnik, Iván; Haro, Miguel Sofo; Suárez, Sergio; Gimenez, Melisa Lucía; Berisso, Mariano Gómez; Lipovetzky, Jose

2018-06-01

In this work we will introduce a novel low cost position sensitive thermal neutron detection technique, based on a Commercial Off The Shelf CMOS image sensor covered with a Gadolinium containing conversion layer. The feasibility of the neutron detection technique implemented in this work has been experimentally demonstrated. A thermal neutron detection efficiency of 11.3% has been experimentally obtained with a conversion layer of 11.6 μm. It was experimentally verified that the thermal neutron detection efficiency of this technique is independent on the intensity of the incident thermal neutron flux, which was confirmed for conversion layers of different thicknesses. Based on the experimental results, a spatial resolution better than 25 μm is expected. This spatial resolution makes the proposed technique specially useful for neutron beam characterization, neutron beam dosimetry, high resolution neutron imaging, and several neutron scattering techniques.

Multifunctional gadolinium-based dendritic macromolecules as liver targeting imaging probes.

PubMed

Luo, Kui; Liu, Gang; He, Bin; Wu, Yao; Gong, Qingyong; Song, Bin; Ai, Hua; Gu, Zhongwei

2011-04-01

The quest for highly efficient and safe contrast agents has become the key factor for successful application of magnetic resonance imaging (MRI). The gadolinium (Gd) based dendritic macromolecules, with precise and tunable nanoscopic sizes, are excellent candidates as multivalent MRI probes. In this paper, a novel series of Gd-based multifunctional peptide dendritic probes (generation 2, 3, and 4) possessing highly controlled structures and single molecular weight were designed and prepared as liver MRI probes. These macromolecular Gd-ligand agents exhibited up to 3-fold increase in T(1) relaxivity comparing to Gd-DTPA complexes. No obvious in vitro cytotoxicity was observed from the measured concentrations. These dendritic probes were further functionalized with multiple galactosyl moieties and led to much higher cell uptake in vitro as demonstrated in T(1)-weighted scans. During in vivo animal studies, the probes provided better signal intensity (SI) enhancement in mouse liver, especially at 60 min post-injection, with the most efficient enhancement from the galactosyl moiety decorated third generation dendrimer. The imaging results were verified with analysis of Gd content in liver tissues. The design strategy of multifunctional Gd-ligand peptide dendritic macromolecules in this study may be used for developing other sensitive MRI probes with targeting capability. Copyright © 2011 Elsevier Ltd. All rights reserved.

Process-Property Relationship for Air Plasma-Sprayed Gadolinium Zirconate Coatings

NASA Astrophysics Data System (ADS)

Dwivedi, Gopal; Tan, Yang; Viswanathan, Vaishak; Sampath, Sanjay

2015-02-01

The continuous need of elevating operating temperature of gas turbine engines has introduced several challenges with the current state-of-the-art yttria-stabilized zirconia (YSZ)-based thermal barrier coatings (TBCs), requiring examination of new TBC material with high temperature phase stability, lower thermal conductivity, and resistance to environmental ash particles. Gadolinium zirconate (Gd2Zr2O7) (GDZ) has been shown to meet many of these requirements, and has, in fact, been successfully implemented in to engine components. However, several fundamental issues related to the process-ability, toughness, and microstructural differences for GDZ when compared to equivalent YSZ coating. This study seeks to critically address the process-structure-property correlations for plasma-sprayed GDZ coating subjected to controlled parametric exploration. Use of in-flight diagnostics coupled with in situ and ex situ coating property monitoring allows examination and comparison of the process-property interplay and the resultant differences between the two TBC compositions. The results indicate that it is feasible to retain material chemistry and fabricate relevant microstructures of interest with GDZ with concomitant performance advantages such as low conductivity, mechanical compliance, sintering resistance, and suppression of environmentally induced damage from ash particles. This study provides a framework for optimal design and manufacturing of emergent multi-layer and multi-material TBCs.

Influence of gamma-irradiation on the non-isothermal decomposition of calcium-gadolinium oxalate

NASA Astrophysics Data System (ADS)

Moharana, S. C.; Praharaj, J.; Bhatta, D.

Thermal decomposition of co-precipitated unirradiated and irradiated Ca-Gd oxalate has been studied by adopting differential thermal analysis (DTA) and thermogravimetric (TG) techniques. The reaction occurs through two stages corresponding to the decomposition of gadolinium oxalate (Gd-Ox) followed by that of calcium oxalate (Ca-Ox). The kinetic parameters for both the stages are calculated by using solid state reaction models and Coats-Redfern's equation. The co-precipitation as well as irradiation alter the DTA peak temperatures and the kinetic parameters of Ca-Ox. The decomposition of Gd-Ox follows the two dimensional Contracting area (R-2) mechanism, while that of Ca-Ox follows the Avrami-Erofeev (A(2)) mechanism (n =2), which are also exhibited by the co-precipitated and irradiated samples. Co-precipitation decreases the energy of activation and the pre-exponential factor of the individual components but the reverse phenomenon takes place upon irradiation of the co-precipitate. The mechanisms underlying the phenomena are explored.

Luminescence studies of rare earth doped yttrium gadolinium mixed oxide phosphor

NASA Astrophysics Data System (ADS)

Som, S.; Choubey, A.; Sharma, S. K.

2012-09-01

This paper reports the photoluminescence and thermoluminescence properties of gamma ray induced rare earth doped yttrium gadolinium mixed oxide phosphor. The europium (Eu3+) was used as rare earth dopant. The phosphor was prepared by chemical co-precipitation method according to the formula (Y2-x-yGdx) O3: Euy3+ (x=0.5; y=0.05). The photoluminescence emission spectrum of the prepared phosphor shows intense peaks in the red region at 615 nm for 5D0→7F2 transitions and the photoluminescence excitation spectra show a broad band located around 220-270 nm for the emission wavelength fixed at 615 nm. The thermoluminescence studies were carried out after irradiating the phosphor by gamma rays in the dose range from 100 Gy to 1 KGy. In the thermoluminescence glow curves, one single peak was observed at about 300 °C of which the intensity increases linearly in the studied dose range of gamma rays. The glow peak was deconvoluted by GlowFit program and the kinetic parameters associated with the deconvoluted peaks were calculated. The kinetic parameters were also calculated by various glow curve shape and heating rate methods.

Modelling of the Gadolinium Fuel Test IFA-681 using the BISON Code

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pastore, Giovanni; Hales, Jason Dean; Novascone, Stephen Rhead

2016-05-01

In this work, application of Idaho National Laboratory’s fuel performance code BISON to modelling of fuel rods from the Halden IFA-681 gadolinium fuel test is presented. First, an overview is given of BISON models, focusing on UO2/UO2-Gd2O3 fuel and Zircaloy cladding. Then, BISON analyses of selected fuel rods from the IFA-681 test are performed. For the first time in a BISON application to integral fuel rod simulations, the analysis is informed by detailed neutronics calculations in order to accurately capture the radial power profile throughout the fuel, which is strongly affected by the complex evolution of absorber Gd isotopes. Inmore » particular, radial power profiles calculated at IFE–Halden Reactor Project with the HELIOS code are used. The work has been carried out in the frame of the collaboration between Idaho National Laboratory and Halden Reactor Project. Some slide have been added as an Appendix to present the newly developed PolyPole-1 algorithm for modeling of intra-granular fission gas release.« less

Phenotypic expression in hypertrophic cardiomyopathy and late gadolinium enhancement on cardiac magnetic resonance.

PubMed

Caetano, Francisca; Botelho, Ana; Trigo, Joana; Silva, Joana; Almeida, Inês; Venâncio, Margarida; Pais, João; Sanches, Conceição; Leitão Marques, António

2014-05-01

The prognostic value of late gadolinium enhancement (LGE) for risk stratification of hypertrophic cardiomyopathy (HCM) patients is the subject of disagreement. We set out to examine the association between clinical and morphological variables, risk factors for sudden cardiac death and LGE in HCM patients. From a population of 78 patients with HCM, we studied 53 who underwent cardiac magnetic resonance. They were divided into two groups according to the presence or absence of LGE. Ventricular arrhythmias and morbidity and mortality during follow-up were analyzed. Patients with LGE were younger at the time of diagnosis (p=0.046) and more often had a family history of sudden death (p=0.008) and known coronary artery disease (p=0.086). On echocardiography they had greater maximum wall thickness (p=0.007) and left atrial area (p=0.037) and volume (p=0.035), and more often presented a restrictive pattern of diastolic dysfunction (p=0.011) with a higher E/É ratio (p=0.003) and left ventricular systolic dysfunction (p=0.038). Cardiac magnetic resonance supported the association between LGE and previous echocardiographic findings: greater left atrial area (p=0.029) and maximum wall thickness (p<0.001) and lower left ventricular ejection fraction (p=0.056). Patients with LGE more often had an implantable cardioverter-defibrillator (ICD) (p=0.015). At follow-up, no differences were found in the frequency of ventricular arrhythmias, appropriate ICD therapies or mortality. The presence of LGE emerges as a risk marker, associated with the classical predictors of sudden cardiac death in this population. However, larger studies are required to confirm its independent association with clinical events. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Prognostic Value of Late Gadolinium Enhancement CMR in Systemic Amyloidosis.

PubMed

Raina, Sameer; Lensing, Shelly Y; Nairooz, Ramez S; Pothineni, Naga Venkata K; Hakeem, Abdul; Bhatti, Sabha; Pandey, Tarun

2016-11-01

The aim of this study was to access the prognostic implication of late gadolinium enhancement (LGE) in patients with systemic amyloidosis undergoing cardiac magnetic resonance (CMR). Cardiac amyloidosis confers significantly worse prognosis in patients with systemic amyloidosis. CMR imaging has emerged as an attractive noninvasive modality to diagnose cardiac involvement in patients with systemic amyloidosis. We performed a systemic review and meta-analysis to evaluate the prognostic role of LGE-CMR imaging in patients with systemic amyloidosis. Electronic databases MEDLINE, PubMed, Embase, and Cochrane were systematically searched to identify studies evaluating the association between LGE-CMR and prognosis in systemic amyloidosis with cardiac involvement. The present study was designed to systematically review and assess the association between LGE and the primary endpoint of all-cause mortality. A random effects model was used to calculate a pooled odds ratio using inverse-variance weighting. Data were included from 7 studies with a total of 425 patients and a mean follow-up of 25 months. Patients had a weighted average age of 64 years and left ventricular ejection fraction of 59.2%; 67% were male. Endomyocardial biopsy was positive for amyloidosis in 20%, whereas LGE was present in 73% of patients. LGE-positive patients had increased overall mortality compared with those without LGE (pooled odds ratio: 4.96; 95% confidence interval [CI]: 1.90 to 12.93; p = 0.001). For the LGE group, the pooled death rate was 0.07 (95% CI: 0.03 to 0.19) events per year and for the LGE+ group, the rate was 0.25 (95% CI: 0.16 to 0.39 per year; p = 0.001). The proportion of patients with cardiac biopsy within each study ranged from 3% to 68%, and the relationship between LGE status and death did not vary according to cardiac biopsy proportion across studies. LGE on CMR in patients with systemic amyloidosis with known or suspected cardiac amyloidosis is associated with increased

The feasibility of in vivo quantification of bone-gadolinium in humans by prompt gamma neutron activation analysis (PGNAA) following gadolinium-based contrast-enhanced MRI

NASA Astrophysics Data System (ADS)

Mostafaei, F.; McNeill, F. E.; Chettle, D. R.; Noseworthy, M. D.; Prestwich, W. V.

2015-11-01

The feasibility of using a 238Pu/Be-based in vivo prompt γ-ray neutron activation analysis (IVNAA) system, previously successfully used for measurements of muscle, for the detection of gadolinium (Gd) in bone was presented. Gd is extensively used in contrast agents in MR imaging. We present phantom measurement data for the measurement of Gd in the tibia. Gd has seven naturally occurring isotopes, of which two have extremely large neutron capture cross sections; 155Gd (14.8% natural abundance (NA), σ= 60,900 barns) and 157Gd (15.65% NA, σ= 254,000 barns). Our previous work focused on muscle but this only informs about the short term kinetics of Gd. We studied the possibility of measuring bone, as it may be a long term storage site for Gd. A human simulating bone phantom set was developed. The phantoms were doped with seven concentrations of Gd of concentrations 0.0, 25, 50, 75, 100, 120 and 150 ppm. Additional elements important for neutron activation analysis, Na, Cl and Ca, were also included to create an overall elemental composition consistent with Reference Man. The overall conclusion is that the potential application of this Pu-Be-based prompt in vivo NAA for the monitoring of the storage and retention of Gd in bone is not feasible.

Role of MRI T2-DRIVE in the assessment of pituitary stalk abnormalities without gadolinium in pituitary diseases.

PubMed

Godano, Elisabetta; Morana, Giovanni; Di Iorgi, Natascia; Pistorio, Angela; Allegri, Anna Elsa Maria; Napoli, Flavia; Gastaldi, Roberto; Calcagno, Annalisa; Patti, Giuseppa; Gallizia, Annalisa; Notarnicola, Sara; Giaccardi, Marta; Noli, Serena; Severino, Mariasavina; Tortora, Domenico; Rossi, Andrea; Maghnie, Mohamad

2018-06-01

To investigate the role of T2-DRIVE MRI sequence in the accurate measurement of pituitary stalk (PS) size and the identification of PS abnormalities in patients with hypothalamic-pituitary disorders without the use of gadolinium. This was a retrospective study conducted on 242 patients who underwent MRI due to pituitary dysfunction between 2006 and 2015. Among 135 eligible patients, 102 showed eutopic posterior pituitary (PP) gland and 33 showed 'ectopic' PP (EPP). Two readers independently measured the size of PS in patients with eutopic PP at the proximal, midpoint and distal levels on pre- and post-contrast T1-weighted as well as T2-DRIVE images; PS visibility was assessed on pre-contrast T1 and T2-DRIVE sequences in those with EPP. The length, height, width and volume of the anterior pituitary (AP), PP height and length and PP area were analyzed. Significant agreement between the two readers was obtained for T2-DRIVE PS measurements in patients with 'eutopic' PP; a significant difference was demonstrated between the intraclass correlation coefficient calculated on the T2-DRIVE and the T1-pre- and post-contrast sequences. The percentage of PS identified by T2-DRIVE in EPP patients was 72.7% compared to 30.3% of T1 pre-contrast sequences. A significant association was found between the visibility of PS on T2-DRIVE and the height of AP. T2-DRIVE sequence is extremely precise and reliable for the evaluation of PS size and the recognition of PS abnormalities; the use of gadolinium-based contrast media does not add significant information and may thus be avoided. © 2018 European Society of Endocrinology.

MicroRNA-155 Inhibition Promoted Wound Healing in Diabetic Rats.

PubMed

Ye, Junna; Kang, Yutian; Sun, Xiaofang; Ni, Pengwen; Wu, Minjie; Lu, Shuliang

2017-06-01

Diabetes leads to amputation in approximately 15% to 20% of patients and is associated with high morbidity and mortality. Thus, improving the quality of wound healing in this condition is essential. Diabetes is associated with acute/chronic inflammation affecting all organs especially the foot, while, inhibition of microRNA-155 (miR-155) has been reported to improve or reduce inflammatory situation. However, the role of miR-155 inhibition in promoting diabetic wound healing is not clear. To further study the potential benefit of miR-155 inhibition, a study of male Sprague-Dawley rats was conducted and diabetes was induced by injection of streptozotocin. Real-time polymerase chain reaction (PCR), hematoxylin and eosin staining and immunohistochemistry were then performed. The PCR results confirmed that miR-155 expression was lower after miR-155 inhibition on days 3, 7, and 13 (all Ps <.05). The wound healing rate between the normal glucose group (N group), diabetic PBS group (PBS group) and the topical miR-155 inhibitor group was compared. Faster healing of cutaneous wounds was observed in the miR-155 inhibitor group than in the PBS group and normal glucose group ( P < .05). In addition, downregulation of inflammatory cells, including neutrophils (MPO-positive) and macrophages (CD68-positive), and upregulation of the angiogenic protein CD31 and markers indicative of fibroblast proliferation and collagen deposition, such as collagen 1, TGF-β1, and α-SMA, were observed. These data permit the observation that miR-155 inhibition possesses the potential to reduce inflammation in acute wounds. This property may benefit the healing of diabetic foot wounds.

Various ligand-coated ultrasmall gadolinium-oxide nanoparticles: Water proton relaxivity and in-vivo T1 MR image

NASA Astrophysics Data System (ADS)

Park, Ja Young; Kim, Sung June; Lee, Gang Ho; Jin, Seonguk; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok

2015-04-01

Surface coating of nanoparticles with ligands is essential in magnetic resonance imaging (MRI) because of solubility in water and biocompatibility. In this study, five organic molecules were used for surface coating of ultrasmall gadolinium-oxide (Gd2O3) nanoparticles (d avg = 2.0 nm). All of the samples showed large longitudinal (r1) and transverse (r2) water proton relaxivities with r2/r1 ratios that were close to one, corresponding to ideal conditions for T1 MRI contrast agents. Finally, in-vivo T1 MR images were acquired to prove the effectiveness of the surface-coated ultrasmall Gd2O3 nanoparticles as a T1 MRI contrast agent.

Diethylenetriaminepentaacetic acid-gadolinium (DTPA-Gd)-conjugated polysuccinimide derivatives as magnetic resonance imaging contrast agents.

PubMed

Lee, Ha Young; Jee, Hye Won; Seo, Sung Mi; Kwak, Byung Kook; Khang, Gilson; Cho, Sun Hang

2006-01-01

Biocompatible polysuccinimide (PSI) derivatives conjugated with diethylenetriaminepentaacetic acid gadolinium (DTPA-Gd) were prepared as magnetic resonance imaging (MRI) contrast agents. In this study, we synthesized PSI derivatives incorporating methoxy-poly(ethylene glycol) (mPEG) as hydrophilic ligand, hexadecylamine as hydrophobic ligand, and DTPA-Gd as contrast agent. PSI was synthesized by the polycondensation polymerization of aspartic acid. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Critical micellization concentrations were determined using fluorescent probes (pyrene). Micelle size and shape were measured by electro-photometer light scattering (ELS) and atomic force microscopy (AFM). The formed micelle size ranged from 100 to 300 nm. The T1-weighted MR images of the phantom prepared with PSI-mPEG-C16-(DTPA-Gd) were obtained in a 3.0 T clinical MR imager, and the conjugates showed a great potential as MRI contrast agents.

Radioluminescence and optical studies of gadolinium calcium phosphate oxyfluoride glasses doped with Sm3+

NASA Astrophysics Data System (ADS)

Meejitpaisan, P.; Insiripong, S.; Kedkaew, C.; Kim, H. J.; Kaewkhao, J.

2017-08-01

Sm3+-doped gadolinium calcium phosphate oxyfluoride glasses have been synthesized and investigated their optical, photo and radioluminescence properties. The glasses were prepared by melt quenching technique at 1400 °C. The characteristic absorption bands of Sm3+ ions originating from the 6H5/2 ground state and occurring absorbed photon in visible light (VIS) and near-infrared (NIR) region with clearly observed from absorption spectra. From the photoluminescence (PL), the glasses showed the emission at 561 (4G5/2→6H5/2), 598 (4G5/2→6H7/2), 644 (4G5/2→6H9/2) and 705 nm (4G5/2→6H11/2). The radioluminescence (RL), emission spectra were corresponding to those from PL measurements. From RL measurement, the integral scintillation efficiency of developed glass was determined at 43% when compared with BGO crystal.

In vitro evaluation of single- and multi-strain probiotics: Inter-species inhibition between probiotic strains, and inhibition of pathogens.

PubMed

Chapman, C M C; Gibson, G R; Rowland, I

2012-08-01

Many studies comparing the effects of single- and multi-strain probiotics on pathogen inhibition compare treatments with different concentrations. They also do not examine the possibility of inhibition between probiotic strains with a mixture. We tested the ability of 14 single-species probiotics to inhibit each other using a cross-streak assay, and agar spot test. We then tested the ability of 15 single-species probiotics and 5 probiotic mixtures to inhibit Clostridium difficile, Escherichia coli and S. typhimurium, using the agar spot test. Testing was done with mixtures created in two ways: one group contained component species incubated together, the other group of mixtures was made using component species which had been incubated separately, equalised to equal optical density, and then mixed in equal volumes. Inhibition was observed for all combinations of probiotics, suggesting that when used as such there may be inhibition between probiotics, potentially reducing efficacy of the mixture. Significant inter-species variation was seen against each pathogen. When single species were tested against mixtures, the multi-species preparations displayed significantly (p < 0.05 or less) greater inhibition of pathogens in 12 out of 24 cases. Despite evidence that probiotic species will inhibit each other when incubated together in vitro, in many cases a probiotic mixture was more effective at inhibiting pathogens than its component species when tested at approximately equal concentrations of biomass. This suggests that using a probiotic mixture might be more effective at reducing gastrointestinal infections, and that creating a mixture using species with different effects against different pathogens may have a broader spectrum of action that a single provided by a single strain. Copyright © 2012 Elsevier Ltd. All rights reserved.

Constructing experimental devices for half-ton synthesis of gadolinium-loaded liquid scintillator and its performance.

PubMed

Park, Young Seo; Jang, Yeong Min; Joo, Kyung Kwang

2018-04-01

This paper describes in brief features of various experimental devices constructed for half-ton synthesis of gadolinium(Gd)-loaded liquid scintillator (GdLS) and also includes the performances and detailed chemical and physical results of a 0.5% high-concentration GdLS. Various feasibility studies on useful apparatus used for loading Gd into solvents have been carried out. The transmittance, Gd concentration, density, light yield, and moisture content were measured for quality control. We show that with the help of adequate automated experimental devices and tools, it is possible to perform ton scale synthesis of GdLS at moderate laboratory scale without difficulty. The synthesized GdLS was satisfactory to meet chemical, optical, and physical properties and various safety requirements. These synthesizing devices can be expanded into massive scale next-generation neutrino experiments of several hundred tons.

Constructing experimental devices for half-ton synthesis of gadolinium-loaded liquid scintillator and its performance

NASA Astrophysics Data System (ADS)

Park, Young Seo; Jang, Yeong Min; Joo, Kyung Kwang

2018-04-01

This paper describes in brief features of various experimental devices constructed for half-ton synthesis of gadolinium(Gd)-loaded liquid scintillator (GdLS) and also includes the performances and detailed chemical and physical results of a 0.5% high-concentration GdLS. Various feasibility studies on useful apparatus used for loading Gd into solvents have been carried out. The transmittance, Gd concentration, density, light yield, and moisture content were measured for quality control. We show that with the help of adequate automated experimental devices and tools, it is possible to perform ton scale synthesis of GdLS at moderate laboratory scale without difficulty. The synthesized GdLS was satisfactory to meet chemical, optical, and physical properties and various safety requirements. These synthesizing devices can be expanded into massive scale next-generation neutrino experiments of several hundred tons.

Inhibited Temperament and Hippocampal Volume in Offspring of Parents with Bipolar Disorder.

PubMed

Kim, Eunjoo; Garrett, Amy; Boucher, Spencer; Park, Min-Hyeon; Howe, Meghan; Sanders, Erica; Kelley, Ryan G; Reiss, Allan L; Chang, Kiki D; Singh, Manpreet K

2017-04-01

Prior studies have suggested that inhibited temperament may be associated with an increased risk for developing anxiety or mood disorder, including bipolar disorder. However, the neurobiological basis for this increased risk is unknown. The aim of this study was to examine temperament in symptomatic and asymptomatic child offspring of parents with bipolar disorder (OBD) and to investigate whether inhibited temperament is associated with aberrant hippocampal volumes compared with healthy control (HC) youth. The OBD group consisted of 45 youth, 24 of whom had current psychiatric symptoms (OBD + s) and 21 without any psychiatric symptoms (OBD - s), and were compared with 24 HC youth. Temperament characteristics were measured by using the Revised Dimensions of Temperament Survey. Magnetic resonance imaging was used to measure hippocampal volumes. The association between temperament and hippocampal volumes was tested by using multiple regression analysis. Compared with the OBD - s group, the OBD + s group had significantly more inhibited temperament traits, less flexibility, more negative mood, and less regular rhythm in their daily routines. In contrast, the OBD - s group was more likely to approach novel situations compared with OBD + s or HC groups. Within the OBD + s group, a more inhibited temperament was associated with smaller right hippocampal volumes. In this study, symptomatic OBD were characterized by an inhibited temperament that was inversely correlated with hippocampal volume. Additional longitudinal studies are needed to determine whether inverse correlations between hippocampal volume and inhibited temperament represent early markers of risk for later developing bipolar disorder.

Selective inhibition of influenza virus protein synthesis by inhibitors of DNA function. [UV radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minor, P.D.; Dimmock, N.J.

1977-05-15

Various known inhibitors of cellular DNA function were shown to inhibit cellular RNA synthesis and influenza (fowl plague) virus multiplication. The drugs were investigated for their effect upon the synthesis of influenza virus proteins. According to this effect they could be classified with previously studied compounds as follows: Group I (ethidium bromide, proflavine, and N-nitroquinoline-N-oxide) inhibited both viral and cellular protein synthesis; Group II (nogalomycin, daunomycin and ..cap alpha..-amanitin) inhibited viral but not cellular protein synthesis, and all viral proteins were inhibited coordinately; Group III (mithramycin, echinomycin, and actinomycin D) inhibited all viral but not cellular protein synthesis at highmore » concentrations, but at a lower critical concentration inhibited the synthesis of viral haemagglutinin, neuraminidase, and M protein preferentially; Group IV(uv irradiation and camptothecin) inhibited the synthesis of viral haemagglutinin, neuraminidase, and M protein, but not other viral proteins, even at high doses. The mode of action of these inhibitors is discussed in relation to the mechanism of the nuclear events upon which influenza virus multiplication is dependent.« less

Correction of false memory for associated word lists by collaborating groups.

PubMed

Weigold, Arne; Russell, Elizabeth J; Natera, Sara N

2014-01-01

Collaborative inhibition is often observed for both correct and false memories. However, research examining the mechanisms by which collaborative inhibition occurs, such as retrieval disruption, reality monitoring, or group filtering, is lacking. In addition, the creation of the nominal groups (i.e., groups artificially developed by combining individuals' recall) necessary for examining collaborative inhibition do not use statistical best practices. Using the Deese-Roediger-McDermott paradigm, we examined percentages of correct and false memories in individuals, collaborative interactive groups, and correctly created nominal groups, as well as the processes that the collaborative interactive groups used to determine which memories to report. Results showed evidence of the collaborative inhibition effect. In addition, analyses of the collaborative interactive groups' discussions found that these groups wrote down almost all presented words but less than half of nonpresented critical words, after discussing them, with nonpresented critical words being stated to the group with lower confidence and rejected by other group members more often. Overall, our findings indicated support for the group filtering hypothesis.

Baicalin Inhibits Haemophilus Parasuis-Induced High-Mobility Group Box 1 Release during Inflammation.

PubMed

Fu, Shulin; Liu, Huashan; Chen, Xiao; Qiu, Yinsheng; Ye, Chun; Liu, Yu; Wu, Zhongyuan; Guo, Ling; Hou, Yongqing; Hu, Chien-An Andy

2018-04-27

Haemophilus parasuis ( H. parasuis ) can cause Glässer’s disease in pigs. However, the molecular mechanism of the inflammation response induced by H. parasuis remains unclear. The high-mobility group box 1 (HMGB1) protein is related to the pathogenesis of various infectious pathogens, but little is known about whether H. parasuis can induce the release of HMGB1 in piglet peripheral blood monocytes. Baicalin displays important anti-inflammatory and anti-microbial activities. In the present study, we investigated whether H. parasuis can trigger the secretion of HMGB1 in piglet peripheral blood monocytes and the anti-inflammatory effect of baicalin on the production of HMGB1 in peripheral blood monocytes induced by H. parasuis during the inflammation response. In addition, host cell responses stimulated by H. parasuis were determined with RNA-Seq. The RNA-Seq results showed that H. parasuis infection provokes the expression of cytokines and the activation of numerous pathways. In addition, baicalin significantly reduced the release of HMGB1 in peripheral blood monocytes induced by H. parasuis . Taken together, our study showed that H. parasuis can induce the release of HMGB1 and baicalin can inhibit HMGB1 secretion in an H. parasuis -induced peripheral blood monocytes model, which may provide a new strategy for preventing the inflammatory disorders induced by H. parasuis .

Self-Gated Late Gadolinium Enhancement at 7T to Image Rats with Reperfused Acute Myocardial Infarction.

PubMed

Wang, Lei; Chen, Yushu; Zhang, Bing; Chen, Wei; Wang, Chunhua; Song, Li; Xu, Ziqian; Zheng, Jie; Gao, Fabao

2018-01-01

A failed electrocardiography (ECG)-trigger often leads to a long acquisition time (TA) and deterioration in image quality. The purpose of this study was to evaluate and optimize the technique of self-gated (SG) cardiovascular magnetic resonance (CMR) for cardiac late gadolinium enhancement (LGE) imaging of rats with myocardial infarction/reperfusion. Cardiovascular magnetic resonance images of 10 rats were obtained using SG-LGE or ECG with respiration double-gating (ECG-RESP-gating) method at 7T to compare differences in image interference and TA between the two methods. A variety of flip angles (FA: 10°-80°) and the number of repetitions (NR: 40, 80, 150, and 300) were investigated to determine optimal scan parameters of SG-LGE technique based on image quality score and contrast-to-noise ratio (CNR). Self-gated late gadolinium enhancement allowed successful scan in 10 (100%) rats. However, only 4 (40%) rats were successfully scanned with the ECG-RESP-gating method. TAs with SG-LGE varied depending on NR used (TA: 41, 82, 154, and 307 seconds, corresponding to NR of 40, 80, 150, and 300, respectively). For the ECG-RESP-gating method, the average TA was 220 seconds. For SG-LGE images, CNR (42.5 ± 5.5, 43.5 ± 7.5, 54 ± 9, 59.5 ± 8.5, 56 ± 13, 54 ± 8, and 41 ± 9) and image quality score (1.85 ± 0.75, 2.20 ± 0.83, 2.85 ± 0.37, 3.85 ± 0.52, 2.8 ± 0.51, 2.45 ± 0.76, and 1.95 ± 0.60) were achieved with different FAs (10°, 15°, 20°, 25°, 30°, 35°, and 40°, respectively). Optimal FAs of 20°-30° and NR of 80 were recommended. Self-gated technique can improve image quality of LGE without irregular ECG or respiration gating. Therefore, SG-LGE can be used an alternative method of ECG-RESP-gating.

Thermal, spectroscopic and laser properties of Nd3+ in gadolinium scandium gallium garnet crystal produced by optical floating zone method

NASA Astrophysics Data System (ADS)

Tian, Li; Wang, Shuxian; Wu, Kui; Wang, Baolin; Yu, Haohai; Zhang, Huaijin; Cai, Huaqiang; Huang, Hui

2013-12-01

A neodymium-doped gadolinium scandium gallium garnet (Nd:GSGG) single crystal with dimensions of Φ 5 × 20 mm2 has been grown by means of optical floating zone (OFZ). X-ray powder diffraction (XRPD) result shows that the as-grown Nd:GSGG crystal possesses a cubic structure with space group Ia3d and a cell parameter of a = 1.2561 nm. Effective elemental segregation coefficients of the Nd:GSGG as-grown crystal were calculated by using X-ray fluorescence (XRF). The thermal properties of the Nd:GSGG crystal were systematically studied by measuring the specific heat, thermal expansion and thermal diffusion coefficient, and the thermal conductivity of this crystal was calculated. The absorption and luminescence spectra of Nd:GSGG were measured at room temperature (RT). By using the Judd-Ofelt (J-O) theory, the theoretical radiative lifetime was calculated and compared with the experimental result. Continuous wave (CW) laser performance was achieved with the Nd:GSGG at the wavelength of 1062 nm when it was pumped by a laser diode (LD). A maximum output power of 0.792 W at 1062 nm was obtained with a slope efficiency of 11.89% under a pump power of 7.36 W, and an optical-optical conversion efficiency of 11.72%.

Hypnotic suggestibility, cognitive inhibition, and dissociation.

PubMed

Dienes, Zoltán; Brown, Elizabeth; Hutton, Sam; Kirsch, Irving; Mazzoni, Giuliana; Wright, Daniel B

2009-12-01

We examined two potential correlates of hypnotic suggestibility: dissociation and cognitive inhibition. Dissociation is the foundation of two of the major theories of hypnosis and other theories commonly postulate that hypnotic responding is a result of attentional abilities (including inhibition). Participants were administered the Waterloo-Stanford Group Scale of Hypnotic Susceptibility, Form C. Under the guise of an unrelated study, 180 of these participants also completed: a version of the Dissociative Experiences Scale that is normally distributed in non-clinical populations; a latent inhibition task, a spatial negative priming task, and a memory task designed to measure negative priming. The data ruled out even moderate correlations between hypnotic suggestibility and all the measures of dissociation and cognitive inhibition overall, though they also indicated gender differences. The results are a challenge for existing theories of hypnosis.

Histology and Gadolinium Distribution in the Rodent Brain After the Administration of Cumulative High Doses of Linear and Macrocyclic Gadolinium-Based Contrast Agents

PubMed Central

Lohrke, Jessica; Frisk, Anna-Lena; Frenzel, Thomas; Schöckel, Laura; Rosenbruch, Martin; Jost, Gregor; Lenhard, Diana Constanze; Sieber, Martin A.; Nischwitz, Volker; Küppers, Astrid; Pietsch, Hubertus

2017-01-01

Objectives Retrospective studies in patients with primary brain tumors or other central nervous system pathologies as well as postmortem studies have suggested that gadolinium (Gd) deposition occurs in the dentate nucleus (DN) and globus pallidus (GP) after multiple administrations of primarily linear Gd-based contrast agents (GBCAs). However, this deposition has not been associated with any adverse effects or histopathological alterations. The aim of this preclinical study was to systematically examine differences between linear and macrocyclic GBCAs in their potential to induce changes in brain and skin histology including Gd distribution in high spatial resolution. Materials and Methods Fifty male Wistar-Han rats were randomly allocated into control (saline, n = 10 rats) and 4 GBCA groups (linear GBCAs: gadodiamide and gadopentetate dimeglumine, macrocyclic GBCAs: gadobutrol and gadoteridol; n = 10 rats per group). The animals received 20 daily intravenous injections at a dose of 2.5 mmol Gd/kg body weight. Eight weeks after the last GBCA administration, the animals were killed, and the brain and skin samples were histopathologically assessed (hematoxylin and eosin; cresyl violet [Nissl]) and by immunohistochemistry. The Gd concentration in the skin, bone, brain, and skeletal muscle samples were analyzed using inductively coupled plasma mass spectroscopy (ICP-MS, n = 4). The spatial Gd distribution in the brain and skin samples was analyzed in cryosections using laser ablation coupled with ICP-MS (LA-ICP-MS, n = 3). For the ultra-high resolution of Gd distribution, brain sections of rats injected with gadodiamide or saline (n = 1) were assessed by scanning electron microscopy coupled to energy dispersive x-ray spectroscopy and transmission electron microscopy, respectively. Results No histological changes were observed in the brain. In contrast, 4 of 10 animals in the gadodiamide group but none of the animals in other groups showed macroscopic and histological

Platinum(II)-gadolinium(III) complexes as potential single-molecular theranostic agents for cancer treatment.

PubMed

Zhu, Zhenzhu; Wang, Xiaoyong; Li, Tuanjie; Aime, Silvio; Sadler, Peter J; Guo, Zijian

2014-11-24

Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)-gadolinium(III) complexes with the formula [{Pt(NH3)2Cl}2GdL](NO3)2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt-Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mM), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd-DTPA. T1-weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt-Gd complexes promising theranostic agents for cancer treatment. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gadolinium oxide decorated multiwalled carbon nanotube/tridoped titania nanocomposites for improved dye degradation under simulated solar light irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mamba, Gcina; Nanotechnology and Water Sustainability Research Unit, College of Engineering, Science and Technology, University of South Africa Florida Science Campus, 1709 Florida; Mbianda, Xavier Yangkou

2016-03-15

Graphical abstract: Illustration of the collaborative effect between MWCNT-Gd and Gd,N,S-TiO{sub 2} towards degradation of AB 74. - Highlights: • MWCNT-Gd/tridoped titania was successfully prepared via a sol-gel method. • XPS revealed the presence of Ti, C, O, S, N and Gd in MWCNT-Gd/Gd,N,S-TiO{sub 2}. • MWCNT-Gd/Gd,N,S-TiO{sub 2} displayed 100% degradation of acid blue 74 in 150 min. • Over 60% TOC removal by MWCNT-Gd/Gd,N,S-TiO{sub 2}. - Abstract: Neodymium/gadolinium/europium, nitrogen and sulphur tridoped titania (Nd/Gd/Eu, N,S-TiO{sub 2}) was hybridised with pre-synthesised gadolinium oxide decorated multiwalled carbon nanotubes (MWCNT-Gd) using a sol–gel method. Subsequent to drying and calcination, composite photocatalysts: MWCNT-Gd/Nd,N,S-TiO{submore » 2}, MWCNT-Gd/Gd,N,S-TiO{sub 2} and MWCNT-Gd/Eu,N,S-TiO{sub 2}, were obtained and characterised using TEM, SEM-EDX, UV–vis, XPS, XRD and FT-IR. Acid blue 74 (AB74) was used as a model dye to investigate the photocatalytic degradation properties of the prepared materials under simulated solar light irradiation. Coupling the different tridoped titania with MWCNT-Gd enhanced their activity compared to MWCNT/TiO{sub 2}, MWCNT-Gd/TiO{sub 2} and MWCNT/Gd,N,S-TiO{sub 2}. MWCNT-Gd/Gd,N,S-TiO{sub 2} showed the highest activity towards AB74 degradation reaching 100% decolourisation after 150 min of irradiation. Total organic carbon analysis revealed that over 50% of the AB74 molecules were completely mineralised after 180 min of irradiation in the presence of MWCNT-Gd/Gd,N,S-TiO{sub 2}.« less

Utility of late gadolinium enhancement in pediatric cardiac MRI.

PubMed

Etesami, Maryam; Gilkeson, Robert C; Rajiah, Prabhakar

2016-07-01

Late gadolinium enhancement (LGE) cardiac magnetic resonance (MR) imaging sequence is increasingly used in the evaluation of pediatric cardiovascular disorders, and although LGE might be a normal feature at the sites of previous surgeries, it is pathologically seen as a result of extracellular space expansion, either from acute cell damage or chronic scarring or fibrosis. LGE is broadly divided into ischemic and non-ischemic patterns. LGE caused by myocardial infarction occurs in a vascular distribution and always involves the subendocardial portion, progressively involving the outer regions in a waveform pattern. Non-ischemic cardiomyopathies can have a mid-myocardial (either linear or patchy), subepicardial or diffuse subendocardial distribution. Idiopathic dilated cardiomyopathy can have a linear mid-myocardial pattern, while hypertrophic cardiomyopathy can have fine, patchy enhancement in hypertrophied and non-hypertrophied segments as well as right ventricular insertion points. Myocarditis and sarcoidosis have a mid-myocardial or subepicardial pattern of LGE. Fabry disease typically affects the basal inferolateral segment while Danon disease typically spares the septum. Pericarditis is characterized by diffuse or focal pericardial thickening and enhancement. Thrombus, the most common non-neoplastic cardiac mass, is characterized by absence of enhancement in all sequences, while neoplastic masses show at least some contrast enhancement, depending on the pathology. Regardless of the etiology, presence of LGE is associated with a poor prognosis. In this review, we describe the technical modifications required for performing LGE cardiac MR sequence in children, review and illustrate the patterns of LGE in children, and discuss their clinical significance.

Nephrogenic systemic fibrosis and class labeling of gadolinium-based contrast agents by the Food and Drug Administration.

PubMed

Yang, Lucie; Krefting, Ira; Gorovets, Alex; Marzella, Louis; Kaiser, James; Boucher, Robert; Rieves, Dwaine

2012-10-01

In 2007, the Food and Drug Administration requested that manufacturers of all approved gadolinium-based contrast agents (GBCAs), drugs widely used in magnetic resonance imaging, use nearly identical text in their product labeling to describe the risk of nephrogenic systemic fibrosis (NSF). Accumulating information about NSF risks led to revision of the labeling text for all of these drugs in 2010. The present report summarizes the basis and purpose of this class-labeling approach and describes some of the related challenges, given the evolutionary nature of the NSF risk evidence. The class-labeling approach for presentation of product risk is designed to decrease the occurrence of NSF and to enhance the safe use of GBCAs in radiologic practice. © RSNA, 2012.

Comparison of MRI properties between derivatized DTPA and DOTA gadolinium-dendrimer conjugates.

PubMed

Nwe, K; Bernardo, M; Regino, C A S; Williams, M; Brechbiel, M W

2010-08-15

In this report we directly compare the in vivo and in vitro MRI properties of gadolinium-dendrimer conjugates of derivatized acyclic diethylenetriamine-N,N',N',N'',N''-pentaacetic acid (1B4M-DTPA) and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (C-DOTA). The metal-ligand chelates were pre-formed in alcohol prior to conjugation to the generation 4 PAMAM dendrimer (G4D), and the dendrimer-based agents were purified by Sephadex(R) G-25 column. The analysis and SE-HPLC data indicated chelate to dendrimer ratios of 30:1 and 28:1, respectively. Molar relaxivity measured at pH 7.4, 22 degrees C, and 3T are comparable (29.5 vs 26.9 mM(-1)s(-1)), and both conjugates are equally viable as MRI contrast agents based on the images obtained. The macrocyclic agent however exhibits a faster rate of clearance in vivo (t(1/2)=16 vs 29 min). Our conclusion is that the macrocyclic-based agent is the more suitable agent for in vivo use for these reasons combined with kinetic inertness associated with the Gd(III) DOTA complex stability properties. Published by Elsevier Ltd.

Engineered gadolinium-doped carbon dots for magnetic resonance imaging-guided radiotherapy of tumors.

PubMed

Du, Fengyi; Zhang, Lirong; Zhang, Li; Zhang, Miaomiao; Gong, Aihua; Tan, Youwen; Miao, Jiawen; Gong, Yuhua; Sun, Mingzhong; Ju, Huixiang; Wu, Chaoyang; Zou, Shenqiang

2017-03-01

The effectiveness of radiotherapy can decrease due to inaccurate positioning of machinery and inherent radioresistance of tumors. To address this issue, we present a novel theranostic nanoplatform based on gadolinium-doped carbon dots (Gd-doped CDs) designed specifically for magnetic resonance imaging (MRI)-guided radiotherapy of tumors. The Gd-doped CDs (∼18 nm) with dispersibility in water and stable photoluminescence were synthesized via a one-step hydrothermal approach. After tail vein injection of the Gd-doped CDs, they exhibited a relatively long circulation time (∼6 h), enabled efficient passive tumor targeting. Gd-doped CDs accumulate in the kidney and could be cleared out of the body from bladder. Importantly, they exhibited favorable biocompatibility with excellent performance in longitudinal relaxivity rate (r 1 ) of 6.45 mM -1 S -1 and radiosensitization enhancements. These results show that Gd-doped CDs are excellent T 1 contrast agents and radiosensitizers, possessing great promise for MRI-guided radiotherapy of tumors. Copyright © 2016 Elsevier Ltd. All rights reserved.

“Off with the Old”: Mindfulness Practice Improves Backward Inhibition

PubMed Central

Greenberg, Jonathan; Reiner, Keren; Meiran, Nachshon

2013-01-01

Mindfulness practice has been linked to reduced depressive rumination and described as involving inhibition of information that has been relevant in the past and is no longer relevant in the present moment. Backward inhibition (BI) is considered to be one of the purest measures of task set inhibition, and impaired BI has been linked to depressive rumination. BI was contrasted with Competitor Rule Suppression (CRS), which is another phenomenon observed in task switching, yet one which involves episodic memory tagging of information that is currently conflicting rather than active inhibition. Although similar at baseline level, a randomly assigned group (n = 38) who underwent an eight session mindfulness training program exhibited improved BI but not CRS compared to a waiting list group (n = 38). Findings indicate that mindfulness improves the specific component of task set inhibition, which has previously been linked to reduced rumination. Implications regarding the potential role of task set inhibition in mediating between mindfulness and reduced rumination, as well as the role of mindfulness in “being in the present moment” are discussed. PMID:23335909

Gadolinium-loaded polymeric nanoparticles modified with Anti-VEGF as multifunctional MRI contrast agents for the diagnosis of liver cancer.

PubMed

Liu, Yongjun; Chen, Zhijin; Liu, Chunxi; Yu, Dexin; Lu, Zaijun; Zhang, Na

2011-08-01

Molecular imaging is essential to increase the sensitivity and selectivity of cancer diagnosis especially in the early stage of tumor. Here, we designed a novel multifunctional polymeric nanoparticle contrast agent (Anti-VEGF PLA-PEG-PLL-Gd NP) simultaneously modified with Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and anti-vascular endothelial growth factor (VEGF) antibody to deliver Gd-DTPA to the tumor area and achieve the early diagnosis of hepatocellular carcinoma (HCC). The Anti-VEGF PLA-PEG-PLL-Gd NPs exhibited high T(1) relaxivity and no obvious cytotoxicity under the experimental concentrations in human hepatocellular carcinoma (HepG2) cells. The results of in vitro cell uptake experiments demonstrated that the uptake process of NPs was both concentration and time depended. Compared with non-targeted NPs, the Anti-VEGF antibody modified NPs showed much higher cell uptake in the HepG2 cells. During in vivo studies, the targeted NPs showed significantly signal intensity enhancement at the tumor site (mouse hepatocarcinoma tumor, H22) compared with non-targeted NPs and Gd-DTPA injection in tumor-bearing mice and the imaging time was significantly prolonged from less than an hour (Gd-DTPA injection group) to 12 h. These results demonstrated that this novel MRI contrast agent Anti-VEGF PLA-PEG-PLL-Gd NPs showed great potential in the early diagnosis of liver tumors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Inhibited solid propellant composition containing beryllium hydride

NASA Technical Reports Server (NTRS)

Thompson, W. W. (Inventor)

1978-01-01

An object of this invention is to provide a composition of beryllium hydride and carboxy-terminated polybutadiene which is stable. Another object of this invention is to provide a method for inhibiting the reactivity of beryllium hydride toward carboxy-terminated polybutadiene. It was found that a small amount of lecithin inhibits the reaction of beryllium hydride with the acid groups in carboxy terminated polybutadiene.

Contribution of hamstring fatigue to quadriceps inhibition following lumbar extension exercise.

PubMed

Hart, Joseph M; Kerrigan, D Casey; Fritz, Julie M; Saliba, Ethan N; Gansneder, Bruce; Ingersoll, Christopher D

2006-01-01

The purpose of this study was to determine the contribution of hamstrings and quadriceps fatigue to quadriceps inhibition following lumbar extension exercise. Regression models were calculated consisting of the outcome variable: quadriceps inhibition and predictor variables: change in EMG median frequency in the quadriceps and hamstrings during lumbar fatiguing exercise. Twenty-five subjects with a history of low back pain were matched by gender, height and mass to 25 healthy controls. Subjects performed two sets of fatiguing isometric lumbar extension exercise until mild (set 1) and moderate (set 2) fatigue of the lumbar paraspinals. Quadriceps and hamstring EMG median frequency were measured while subjects performed fatiguing exercise. A burst of electrical stimuli was superimposed while subjects performed an isometric maximal quadriceps contraction to estimate quadriceps inhibition after each exercise set. Results indicate the change in hamstring median frequency explained variance in quadriceps inhibition following the exercise sets in the history of low back pain group only. Change in quadriceps median frequency explained variance in quadriceps inhibition following the first exercise set in the control group only. In conclusion, persons with a history of low back pain whose quadriceps become inhibited following lumbar paraspinal exercise may be adapting to the fatigue by using their hamstring muscles more than controls. Key PointsA neuromuscular relationship between the lumbar paraspinals and quadriceps while performing lumbar extension exercise may be influenced by hamstring muscle fatigue.QI following lumbar extension exercise in persons with a history of LBP group may involve significant contribution from the hamstring muscle group.More hamstring muscle contribution may be a necessary adaptation in the history of LBP group due to weaker and more fatigable lumbar extensors.

Osteoprotegerin inhibits bone resorption and prevents tumor development in a xenogenic model of Ewing's sarcoma by inhibiting RANKL

PubMed Central

Picarda, Gaëlle; Matous, Etienne; Amiaud, Jérôme; Charrier, Céline; Lamoureux, François; Heymann, Marie-Françoise; Tirode, Franck; Pitard, Bruno; Trichet, Valérie; Heymann, Dominique; Redini, Françoise

2013-01-01

Ewing's sarcoma (ES) associated with high osyeolytic lesions typically arises in the bones of children and adolescents. The development of multi-disciplinary therapy has increased current long-term survival rates to greater than 50% but only 20% for high risk group patients (relapse, metastases, etc.). Among new therapeutic approaches, osteoprotegerin (OPG), an anti-bone resorption molecule may represent a promising candidate to inhibit RANKL-mediated osteolytic component of ES and consequently to limit the tumor development. Xenogenic orthotopic models of Ewing's sarcoma were induced by intra-osseous injection of human TC-71 ES cells. OPG was administered in vivo by non-viral gene transfer using an amphiphilic non ionic block copolymer. ES bearing mice were assigned to controls (no treatment, synthetic vector alone or F68/empty pcDNA3.1 plasmid) and hOPG treated groups. A substantial but not significant inhibition of tumor development was observed in the hOPG group as compared to control groups. Marked bone lesions were revealed by micro-computed tomography analyses in control groups whereas a normal bone micro-architecture was preserved in the hOPG treated group. RANKL over-expressed in ES animal model was expressed by tumor cells rather than by host cells. However, TRAIL present in the tumor microenvironment may interfere with OPG effect on tumor development and bone remodeling via RANKL inhibition. In conclusion, the use of a xenogenic model of Ewing's sarcoma allowed discriminating between the tumor and host cells responsible for the elevation of RANKL production observed in this tumor and demonstrated the relevance of blocking RANKL by OPG as a promising therapy in ES. PMID:26909278

Lattice dynamics of a rigid-ion model for gadolinium molybdate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boyer, L.L.; Hardy, J.R.

Calculations are presented which support the view that the ferroelectric phase tnnnsition in gadolinium molybdate (GMO) arises from the softening and ultimate instability of a doubly degenerate zone-edge mode of the high- temperature paraelectric phase. A rigid-ion model was used in which the short- range force constants are obtained from a detailed knowledge of the crystal structure together wiih the conditions imposed by the requirement that the crystal must be in static equilibrium under the combined influence of both Coulomb and short-range forces. Results show that this type of approach is very useful when one is dealing with complex structuresmore » such as GMO, which has thirty- four ions per unit cell in the paraelectric phase. In view of the simplicity of the model, a surprisingly good correlation with experimental results was obtained. In particular, the calculated zone-center frequencies reproduce the basic features of the observed Raman spectruna. Dispersion curves are presented which show a pronounced softening of two phonon branches which become doubly degenerate at the M point, in agreement with inelastic neutron scattering. The displacements associated wiih the soft M-point modes correlate with the difference in the structures of the high- and low-temperature phases determined by x-ray diffraction. This provides further evidence that the ferroelectric domains in GMO are to be interpreted as frozen-in'' soft zoneboundary modes of the paraelectric phase. (auth)« less

Blockade of invariant TCR-CD1d interaction specifically inhibits antibody production against blood group A carbohydrates

PubMed Central

Tazawa, Hirofumi; Irei, Toshimitsu; Tanaka, Yuka; Igarashi, Yuka; Tashiro, Hirotaka

2013-01-01

Previously, we detected B cells expressing receptors for blood group A carbohydrates in the CD11b+CD5+ B-1a subpopulation in mice, similar to that in blood group O or B in humans. In the present study, we demonstrate that CD1d-restricted natural killer T (NKT) cells are required to produce anti-A antibodies (Abs), probably through collaboration with B-1a cells. After immunization of wild-type (WT) mice with human blood group A red blood cells (A-RBCs), interleukin (IL)-5 exclusively and transiently increased and the anti-A Abs were elevated in sera. However, these reactions were not observed in CD1d−/− mice, which lack NKT cells. Administration of anti-mouse CD1d blocking monoclonal Abs (mAb) prior to immunization abolished IL-5 production by NKT cells and anti-A Ab production in WT mice. Administration of anti-IL-5 neutralizing mAb also diminished anti-A Ab production in WT mice, suggesting that IL-5 secreted from NKT cells critically regulates anti-A Ab production by B-1a cells. In nonobese diabetic/severe combined immunodeficient (NOD/SCID/γcnull) mice, into which peripheral blood mononuclear cells from type O human volunteers were engrafted, administration of anti-human CD1d mAb prior to A-RBC immunization completely inhibited anti-A Ab production. Thus, anti-CD1d treatment might constitute a novel approach that could help in evading Ab-mediated rejection in ABO-incompatible transplant recipients. PMID:23943651

Brief report: Response inhibition and processing speed in children with motor difficulties and developmental coordination disorder.

PubMed

Bernardi, Marialivia; Leonard, Hayley C; Hill, Elisabeth L; Henry, Lucy A

2016-01-01

A previous study reported that children with poor motor skills, classified as having motor difficulties (MD) or Developmental Coordination Disorder (DCD), produced more errors in a motor response inhibition task compared to typically developing (TD) children but did not differ in verbal inhibition errors. The present study investigated whether these groups differed in the length of time they took to respond in order to achieve these levels of accuracy, and whether any differences in response speed could be explained by generally slow information processing in children with poor motor skills. Timing data from the Verbal Inhibition Motor Inhibition test were analyzed to identify differences in performance between the groups on verbal and motor inhibition, as well as on processing speed measures from standardized batteries. Although children with MD and DCD produced more errors in the motor inhibition task than TD children, the current analyses found that they did not take longer to complete the task. Children with DCD were slower at inhibiting verbal responses than TD children, while the MD group seemed to perform at an intermediate level between the other groups in terms of verbal inhibition speed. Slow processing speed did not account for these group differences. Results extended previous research into response inhibition in children with poor motor skills by explicitly comparing motor and verbal responses, and suggesting that slow performance, even when accurate, may be attributable to an inefficient way of inhibiting responses, rather than slow information processing speed per se.

Frontal white matter damage impairs response inhibition in children following traumatic brain injury.

PubMed

Lipszyc, Jonathan; Levin, Harvey; Hanten, Gerri; Hunter, Jill; Dennis, Maureen; Schachar, Russell

2014-05-01

Inhibition, the ability to suppress inappropriate cognitions or behaviors, can be measured using computer tasks and questionnaires. Inhibition depends on the frontal cortex, but the role of the underlying white matter (WM) is unclear. We assessed the specific impact of frontal WM damage on inhibition in 29 children with moderate-to-severe traumatic brain injury (15 with and 14 without frontal WM damage), 21 children with orthopedic injury, and 29 population controls. We used the Stop Signal Task to measure response inhibition, the Behavior Rating Inventory of Executive Function to assess everyday inhibition, and T2 fluid-attenuated inversion recovery magnetic resonance imaging to identify lesions. Children with frontal WM damage had impaired response inhibition compared with all other groups and poorer everyday inhibition than the orthopedic injury group. Frontal WM lesions most often affected the superior frontal gyrus. These results provide evidence for the critical role of frontal WM in inhibition.

Heavy drinking is associated with deficient response inhibition in women but not in men.

PubMed

Nederkoorn, Chantal; Baltus, Marcus; Guerrieri, Ramona; Wiers, Reinout W

2009-09-01

Poor response inhibition has been associated with a wide range of problem behaviours, including addictive behaviours, and could represent a general vulnerability factor. Standard tests of response inhibition have used neutral stimuli. Here we tested whether a deficit in response inhibition in heavy drinkers would be stronger for stimuli related to their problem (alcohol) or not. Response inhibition was assessed with a stop signal task, using four classes of pictures: alcohol-related, soft drinks, erotic (control appetitive categories) and neutral pictures. Participants were 32 heavy and 32 light drinkers. An equal amount of men and women were tested in both drinking groups, in view of recent studies reporting that response disinhibition may be most pronounced in heavy drinking women. Main results were first that no domain-specific differences in response inhibition were found in both groups. Second, heavy drinking females showed stronger response inhibition deficits than other groups. Results are discussed in light of a possible gender difference in response inhibition as a risk factor for addictive behaviours.

Do motivational incentives reduce the inhibition deficit in ADHD?

PubMed

Shanahan, Michelle A; Pennington, Bruce F; Willcutt, Erik W

2008-01-01

The primary goal of this study was to test three competing theories of ADHD: the inhibition theory, the motivational theory, and a dual deficit theory. Previous studies have produced conflicting findings about the effects of incentives on executive processes in ADHD. In the present study of 25 children with ADHD and 30 typically developing controls, motivation was manipulated within the Stop Task. Stop signal reaction time was examined, as well as reaction time, its variability, and the number of errors in the primary choice reaction time task. Overall, the pattern of results supported the inhibition theory over the motivational or dual deficit hypotheses, as main effects of group were found for most key variables (ADHD group was worse), whereas the group by reward interaction predicted by the motivational and dual deficit accounts was not found. Hence, as predicted by the inhibition theory, children with ADHD performed worse than controls irrespective of incentives.

Induction of sister chromatid exchange in the presence of gadolinium-DTPA and its reduction by dimethyl sulfoxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamazaki, Etsuo; Fukuda, Hozumi; Shibuya, Hitoshi

The authors investigate the frequency of sister chromatid exchange (SCE) after the addition of gadolinium (Gd)-DTPA to venous blood samples. Venous blood was obtained from nonsmokers. Samples were incubated with Gd-DTPA alone or in combination with mitomycin C, cytarabine, and dimethyl sulfoxide (DMSO), and then evaluated for SCEs. The frequency of SCE increased with the concentration of Gd-DTPA and as each chemotherapeutic agent was added. Sister chromatid exchange frequencies were lower when the blood was treated with a combination of Gd-DTPA and DMSO compared with Gd-DTPA alone. The increase in frequency of SCE seen after the addition of Gd-DTPA wasmore » decreased by the addition of DMSO, indicating the production of hydroxyl radicals. The effect likely is dissociation-related. 14 refs., 6 tabs.« less

[Curcumin inhibited rat colorectal carcinogenesis by activating PPAR-γ: an experimental study].

PubMed

Liu, Liu-bin; Duan, Chang-nong; Ma, Zeng-yi; Xu, Gang

2015-04-01

To explore the chemopreventive effect of curcumin on DMH induced colorectal carcinogenesis and the underlining mechanism. Totally 40 Wistar rats were divided into the model group and the curcumin group by random digit table, 20 in each group. Meanwhile, a normal control group was set up (n =10). A colorectal cancer model was induced by subcutaneously injecting 20 mg/kg DMH. The tumor incidence and the inhibition rate were calculated. The effect of curcumin on the expression of peroxisome proliferator-activated receptor gamma (PPARγ) in rat colon mucosal tissues was observed using immunohistochemistry and Western blot. HT 29 cell line were cultured and divided into a control group, the curcumin + GW9662 (2-chloro-5-nitro-N-4-phenylbenzamide) intervention group, and the curcumin group. The inhibition of different concentrations curcumin on HT29 cell line was detected using MTT. The expression of curcumin on PPARy was also detected using Western blot. The tumor incidence was 80. 00% (12/15 cases) in the model group, obviously higher than that of the curcumin group (58. 82%, 10/17 cases, P <0. 05). The inhibition rate of curcumin on DMH induced colorected carcinoma reached 26. 46%. Compared with the normal control group, the expression of PPARγ protein was significantly increased in the curcumin group and the model group (P <0. 01). Compared with the model group at the same time point, the expression of PPARy protein was significantly enhanced in the curcumin group (P <0. 05). MTT analysis showed that curcumin could inhibit the proliferation of in vitro HT 29 cells in dose and time dependent manners. The expression of PPARy protein was significantly increased in the GW9662 group and the curcumin group, showing statistical difference when compared with the normal control group (P <0. 01). Compared with the GW9662 group, the expression of PPARγ protein was significantly increased in the curcumin group (P <0. 01). Curcumin could inhibit DMH-induced rat colorectal

Gadolinium and ruthenium red attenuate remote hind limb preconditioning-induced cardioprotection: possible role of TRP and especially TRPV channels.

PubMed

Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

2016-08-01

Remote ischemic preconditioning is a well reported therapeutic strategy that induces cardioprotective effects but the underlying intracellular mechanisms have not been widely explored. The current study was designed to investigate the involvement of TRP and especially TRPV channels in remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus (4 alternate cycles of inflation and deflation of 5 min each) was delivered using a blood pressure cuff tied on the hind limb of the anesthetized rat. Using Langendorff's system, the heart was perfused and subjected to 30-min ischemia and 120-min reperfusion. The myocardial injury was assessed by measuring infarct size, lactate dehydrogenase (LDH), creatine kinase (CK), LVDP, +dp/dtmax, -dp/dtmin, heart rate, and coronary flow rate. Gadolinium, TRP blocker, and ruthenium red, TRPV channel blocker, were employed as pharmacological tools. Remote hind limb preconditioning significantly reduced the infarct size, LDH release, CK release and improved coronary flow rate, hemodynamic parameters including LVDP, +dp/dtmax, -dp/dtmin, and heart rate. However, gadolinium (7.5 and 15 mg kg(-1)) and ruthenium red (4 and 8 mg kg(-1)) significantly attenuated the cardioprotective effects suggesting the involvement of TRP especially TRPV channels in mediating remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus possibly activates TRPV channels on the heart or sensory nerve fibers innervating the heart to induce cardioprotective effects. Alternatively, remote hind limb preconditioning stimulus may also activate the mechanosensitive TRP and especially TRPV channels on the sensory nerve fibers innervating the skeletal muscles to trigger cardioprotective neurogenic signaling cascade. The cardioprotective effects of remote hind limb preconditioning may be mediated via activation of mechanosensitive TRP and especially TRPV channels.

Intraindividual Analysis of Signal Intensity Changes in the Dentate Nucleus After Consecutive Serial Applications of Linear and Macrocyclic Gadolinium-Based Contrast Agents.

PubMed

Radbruch, Alexander; Weberling, Lukas D; Kieslich, Pascal J; Hepp, Johanna; Kickingereder, Philipp; Wick, Wolfgang; Schlemmer, Heinz-Peter; Bendszus, Martin

2016-11-01

, whereas subsequent applications of the macrocyclic GBCAs gadobutrol or gadoterate meglumine in the same patients were not. Rather, the current data tentatively suggest a decrease in preexisting hyperintensities over time when linear GBCAs are changed to macrocyclic GBCAs, potentially indicating a washout effect or precipitation of gadolinium. Future patient studies need to include control groups to replicate the present results, and additional animal studies should be conducted to clarify the underlying mechanism of the proposed SI decrease.

Low-Molecular-Weight Iron Chelates May Be an Alternative to Gadolinium-based Contrast Agents for T1-weighted Contrast-enhanced MR Imaging.

PubMed

Boehm-Sturm, Philipp; Haeckel, Akvile; Hauptmann, Ralf; Mueller, Susanne; Kuhl, Christiane K; Schellenberger, Eyk A

2018-02-01

Purpose To synthesize two low-molecular-weight iron chelates and compare their T1 contrast effects with those of a commercial gadolinium-based contrast agent for their applicability in dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging. Materials and Methods The animal experiments were approved by the local ethics committee. Two previously described iron (Fe) chelates of pentetic acid (Fe-DTPA) and of trans-cyclohexane diamine tetraacetic acid (Fe-tCDTA) were synthesized with stability constants several orders of magnitude higher than those of gadolinium-based contrast agents. The T1 contrast effects of the two chelates were compared with those of gadopentetate dimeglumine in blood serum phantoms at 1.5 T, 3 T, and 7 T. For in vivo studies, a human breast cancer cell line (MDA-231) was implanted in five mice per group. The dynamic contrast effects of the chelates were compared by performing DCE MR imaging with intravenous application of Fe-DTPA or Fe-tCDTA on day 1 and DCE MR imaging in the same tumors with gadopentetate dimeglumine on day 2. Quantitative DCE maps were generated with software and were compared by means of a one-tailed Pearson correlation test. Results Relaxivities in serum (0.94 T at room temperature) of Fe-tCDTA (r1 = 2.2 mmol -1 · sec -1 , r2 = 2.5 mmol -1 · sec -1 ) and Fe-DTPA (r1 = 0.9 mmol -1 · sec -1 , r2 = 0.9 mmol -1 · sec -1 ) were approximately twofold and fivefold lower, respectively, compared with those of gadopentetate dimeglumine (r1 = 4.1 mmol -1 · sec -1 , r2 = 4.8 mmol -1 · sec -1 ). Used at moderately higher concentrations, however, iron chelates generated similar contrast effects at T1-weighted MR imaging in vitro in serum, in vivo in blood, and for DCE MR imaging of breast cancer xenografts. The volume transfer constant values for Fe-DTPA and Fe-tCDTA in the same tumors correlated well with those observed for gadopentetate dimeglumine (Fe-tCDTA Pearson R, 0.99; P = .0003; Fe-DTPA Pearson R, 0.97; P

Behavioral inhibition and childhood stuttering

PubMed Central

Choi, Dahye; Conture, Edward G.; Walden, Tedra A.; Lambert, Warren E.; Tumanova, Victoria

2013-01-01

Purpose The purpose of this study was to assess the relation of behavioral inhibition to stuttering and speech/language output in preschool-age children who do (CWS) and do not stutter (CWNS). Method Participants were preschool-age (ages 36 to 68 months), including 26 CWS (22 males) and 28 CWNS (13 males). Participants’ behavioral inhibition (BI) was assessed by measuring the latency to their sixth spontaneous comment during conversation with an unfamiliar experimenter, using methodology developed by Kagan, Reznick, and Gibbons (1989). In addition to these measures of BI, each participant’s stuttered and non-stuttered disfluencies and mean length of utterance (in morphemes) were assessed. Results Among the more salient findings, it was found that (1) there was no significant difference in BI between preschool-age CWS and CWNS as a group, (2) when extremely high versus low inhibited children were selected, there were more CWS with higher BI and fewer CWS with lower BI when compared to their CWNS peers, and (3) more behaviorally inhibited CWS, when compared to less behaviorally inhibited CWS, exhibited more stuttering. Conclusions Findings are taken to suggest that one aspect of temperament (i.e., behavioral inhibition) is exhibited by some preschool-age CWS and that these children stutter more than CWS with lower behavioral inhibition. The present results seem to support continued study of the association between young children’s temperamental characteristics and stuttering, the diagnostic entity (i.e., CWS versus CWNS), as well as stuttering, the behavior (e.g., frequency of stuttered disfluencies). PMID:23773669

Grouped exposed metal heaters

DOEpatents

Vinegar, Harold J.; Coit, William George; Griffin, Peter Terry; Hamilton, Paul Taylor; Hsu, Chia-Fu; Mason, Stanley Leroy; Samuel, Allan James; Watkins, Ronnie Wade

2010-11-09

A system for treating a hydrocarbon containing formation is described. The system includes two or more groups of elongated heaters. The group includes two or more heaters placed in two or more openings in the formation. The heaters in the group are electrically coupled below the surface of the formation. The openings include at least partially uncased wellbores in a hydrocarbon layer of the formation. The groups are electrically configured such that current flow through the formation between at least two groups is inhibited. The heaters are configured to provide heat to the formation.

Grouped exposed metal heaters

DOEpatents

Vinegar, Harold J [Bellaire, TX; Coit, William George [Bellaire, TX; Griffin, Peter Terry [Brixham, GB; Hamilton, Paul Taylor [Houston, TX; Hsu, Chia-Fu [Granada Hills, CA; Mason, Stanley Leroy [Allen, TX; Samuel, Allan James [Kular Lumpar, ML; Watkins, Ronnie Wade [Cypress, TX

2012-07-31

A system for treating a hydrocarbon containing formation is described. The system includes two or more groups of elongated heaters. The group includes two or more heaters placed in two or more openings in the formation. The heaters in the group are electrically coupled below the surface of the formation. The openings include at least partially uncased wellbores in a hydrocarbon layer of the formation. The groups are electrically configured such that current flow through the formation between at least two groups is inhibited. The heaters are configured to provide heat to the formation.

Induction of skeletal abnormalities and autophagy in Paracentrotus lividus sea urchin embryos exposed to gadolinium.

PubMed

Martino, Chiara; Chiarelli, Roberto; Bosco, Liana; Roccheri, Maria Carmela

2017-09-01

Gadolinium (Gd) concentration is constantly increasing in the aquatic environment, becoming an emergent environmental pollutant. We investigated the effects of Gd on Paracentrotus lividus sea urchin embryos, focusing on skeletogenesis and autophagy. We observed a delay of biomineral deposition at 24 hours post fertilization (hpf), and a strong impairment of skeleton growth at 48 hpf, frequently displayed by an asymmetrical pattern. Skeleton growth was found partially resumed in recovery experiments. The mesodermal cells designated to biomineralization were found correctly migrated at 24 hpf, but not at 48 hpf. Western blot analysis showed an increase of the LC3-II autophagic marker at 24 and 48 hpf. Confocal microscopy studies confirmed the increased number of autophagolysosomes and autophagosomes. Results show the hazard of Gd in the marine environment, indicating that Gd is able to affect different aspects of sea urchin development: morphogenesis, biomineralization, and stress response through autophagy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of cardiogoniometry and electrocardiography with perfusion cardiac magnetic resonance imaging and late gadolinium enhancement.

PubMed

Birkemeyer, Ralf; Toelg, Ralph; Zeymer, Uwe; Wessely, Rainer; Jäckle, Sebastian; Hairedini, Bajram; Lübke, Mike; Aßfalg, Manfred; Jung, Werner

2012-12-01

Cardiogoniometry (CGM) is a spatio-temporal five-lead resting electrocardiographic method utilizing automated analysis. The purpose of this study was to determine CGM's and electrocardiography (ECG)'s accuracy for detecting myocardial ischaemia and/or lesions in comparison with perfusion cardiac magnetic resonance imaging (CMRI) and late gadolinium enhancement (LGE). Forty (n= 40) patients with suspected or known stable coronary artery disease were examined by CGM and resting ECG directly prior to CMRI including adenosine stress perfusion (ASP) and LGE. The investigators visually reading the CMRI were blinded to the CGM and ECG results. Half of the patients (n= 20) had a normal CMRI while the other half presented with either abnormal ASP and/or detectable LGE. Cardiogoniometry yielded an accuracy of 83% (sensitivity 70%) and ECG of 63% (sensitivity 35%) compared with CMRI. In this pilot study CGM compares more favourably than ECG with the detection of ischaemia and/or structural myocardial lesions on CMRI.

Comparison of MRI properties between derivatized DTPA and DOTA gadolinium-dendrimer conjugates

PubMed Central

Nwe, K.; Bernardo, M; Regino, C. A. S.; Williams, M; Brechbiel, M. W.

2010-01-01

In this report we directly compare the in vivo and in vitro MRI properties of gadolinium-dendrimer conjugates of derivatized acyclic diethylenetriamine-N,N’,N’,N’’, N’’-pentaacetic acid (1B4M-DTPA) and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid (C-DOTA). The metal-ligand chelates were pre-formed in alcohol prior to conjugation to the generation 4 PAMAM dendrimer (G4D), and the dendrimer-based agents were purified by Sephadex® G-25 column. The analysis and SE-HPLC data indicated chelate to dendrimer ratios of 30:1 and 28:1 respectively. Molar relaxivity measured at pH 7.4, 22°C, and 3T are comparable (29.5 vs. 26.9 mM−1s−1), and both conjugates are equally viable as MRI contrast agents based on the images obtained. The macrocyclic agent however exhibits a faster rate of clearance in vivo (t1/2 = 16 vs. 29 min.). Our conclusion is that the macrocyclic-based agent is the more suitable agent for in vivo use for these reasons combined with kinetic inertness associated with the Gd(III) DOTA complex stability properties. PMID:20663676

[Optical and spectral parameters in Ce3+ -doped gadolinium gallium aluminum garnet glass-ceramics].

PubMed

Gong, Hua; Zhao, Xin; Yu, Xiao-bo; Setsuhisa, Tanabe; Lin, Hai

2010-01-01

The crystalline phases of Ce3+ -doped gadolinium gallium aluminum garnet (GGAG) glass-ceramics were investigated by X-ray diffraction, and the fluorescence spectra were recorded under the pumping of blue light-emitting diode (LED) using an integrating sphere of 10-inch in diameter, which connected to a CCD detector. The spectral power distribution of the glass-ceramics was obtained from the measured spectra first, and then the quantum yield was derived based on the photon distribution. The quantum yield of Ce3+ emission in GGAG glass-ceramics is 29.2%, meanwhile, the color coordinates and the correlated color temperature (CCT) of combined white light were proved to be x = 0.319, y = 0.349 and 6086 K, respectively. Although the quantum yield is a little smaller than the value in Ce3+ -doped YAG glass-ceramics, the CCT of the combined white light is much smaller than that in the latter. The optical behavior of GGAG glass-ceramics provides new vision for developing comfortable LED lighting devices.

Heavy-ion beam induced effects in enriched gadolinium target films prepared by molecular plating

NASA Astrophysics Data System (ADS)

Mayorov, D. A.; Tereshatov, E. E.; Werke, T. A.; Frey, M. M.; Folden, C. M.

2017-09-01

A series of enriched gadolinium (Gd, Z = 64) targets was prepared using the molecular plating process for nuclear physics experiments at the Cyclotron Institute at Texas A&M University. After irradiation with 48Ca and 45Sc projectiles at center-of-target energies of Ecot = 3.8-4.7 MeV/u, the molecular films displayed visible discoloration. The morphology of the films was examined and compared to the intact target surface. The thin films underwent a heavy-ion beam-induced density change as identified by scanning electron microscopy and α-particle energy loss measurements. The films became thinner and more homogenous, with the transformation occurring early on in the irradiation. This transformation is best described as a crystalline-to-amorphous phase transition induced by atomic displacement and destruction of structural order of the original film. The chemical composition of the thin films was surveyed using energy dispersive spectroscopy and X-ray diffraction, with the results confirming the complex chemistry of the molecular films previously noted in other publications.

Antenna Effect on the Organic Spacer-Modified Eu-Doped Layered Gadolinium Hydroxide for the Detection of Vanadate Ions over a Wide pH Range.

PubMed

Jeong, Heejin; Lee, Byung-Il; Byeon, Song-Ho

2016-05-04

The excitation of the adsorbed vanadate group led to the red emission arising from the efficient energy transfer to Eu-doped layered gadolinium hydroxide (LGdH:Eu). This light-harvesting antenna effect allowed LGdH:Eu to detect selectively a vanadate in aqueous solution at different pHs. Because vanadate exists in various forms by extensive oligomerization and protonation reactions in aqueous solution depending on pH, it is important to detect a vanadate regardless of its form over a wide pH range. In particular, spacer molecules with long alkyl chains greatly facilitated access of a vanadate antenna into the interlayer surface of LGdH:Eu. The concomitant increase in adsorption capacity of LGdH:Eu achieved a strong antenna effect of vanadate on the red emission from Eu(3+). When a suspension containing LGdH:Eu nanosheets (1.0 g/L) was used, the vanadate concentration down to 1 × 10(-5) M could even be visually monitored, and the detection limit based on the (5)D0 → (7)F2 emission intensity could reach 4.5 × 10(-8) M.

High performance magneto-fluorescent nanoparticles assembled from terbium and gadolinium 1,3-diketones

PubMed Central

Zairov, Rustem; Mustafina, Asiya; Shamsutdinova, Nataliya; Nizameev, Irek; Moreira, Beatriz; Sudakova, Svetlana; Podyachev, Sergey; Fattakhova, Alfia; Safina, Gulnara; Lundstrom, Ingemar; Gubaidullin, Aidar; Vomiero, Alberto

2017-01-01

Polyelectrolyte-coated nanoparticles consisting of terbium and gadolinium complexes with calix[4]arene tetra-diketone ligand were first synthesized. The antenna effect of the ligand on Tb(III) green luminescence and the presence of water molecules in the coordination sphere of Gd(III) bring strong luminescent and magnetic performance to the core-shell nanoparticles. The size and the core-shell morphology of the colloids were studied using transmission electron microscopy and dynamic light scattering. The correlation between photophysical and magnetic properties of the nanoparticles and their core composition was highlighted. The core composition was optimized for the longitudinal relaxivity to be greater than that of the commercial magnetic resonance imaging (MRI) contrast agents together with high level of Tb(III)-centered luminescence. The tuning of both magnetic and luminescent output of nanoparticles is obtained via the simple variation of lanthanide chelates concentrations in the initial synthetic solution. The exposure of the pheochromocytoma 12 (PC 12) tumor cells and periphery human blood lymphocytes to nanoparticles results in negligible effect on cell viability, decreased platelet aggregation and bright coloring, indicating the nanoparticles as promising candidates for dual magneto-fluorescent bioimaging. PMID:28091590

Mechanical delivery of aerosolized gadolinium-DTPA for pulmonary ventilation assessment in MR imaging.

PubMed

Haage, P; Adam, G; Karaagac, S; Pfeffer, J; Glowinski, A; Döhmen, S; Günther, R W

2001-04-01

To evaluate a new technique with mechanical administration of aerosolized gadolinium (Gd)-DTPA for MR visualization of lung ventilation. Ten experimental procedures were performed in six domestic pigs. Gd-DTPA was aerosolized by a small-particle generator. The intubated animals were mechanically aerosolized with the nebulized contrast agent and studied on a 1.5-T MR imager. Respiratory gated T1-weighted turbo spin-echo images were obtained before, during, and after contrast administration. Pulmonary signal intensity (SI) changes were calculated for corresponding regions of both lungs. Homogeneity of aerosol distribution was graded independently by two radiologists. To achieve a comparable SI increase as attained in previous trials that used manual aerosol ventilation, a ventilation period of 20 minutes (formerly 30 minutes) was sufficient. Mean SI changes of 116% were observed after that duration. Contrast delivery was rated evenly distributed in all cases by the reviewers. The feasibility of applying Gd-DTPA as a contrast agent to demonstrate pulmonary ventilation in large animals has been described before. The results of this refined technique substantiate the potential of Gd-based ventilation MR imaging by improving aerosol distribution and shortening the nebulization duration in the healthy lung.

High performance magneto-fluorescent nanoparticles assembled from terbium and gadolinium 1,3-diketones

NASA Astrophysics Data System (ADS)

Zairov, Rustem; Mustafina, Asiya; Shamsutdinova, Nataliya; Nizameev, Irek; Moreira, Beatriz; Sudakova, Svetlana; Podyachev, Sergey; Fattakhova, Alfia; Safina, Gulnara; Lundstrom, Ingemar; Gubaidullin, Aidar; Vomiero, Alberto

2017-01-01

Polyelectrolyte-coated nanoparticles consisting of terbium and gadolinium complexes with calix[4]arene tetra-diketone ligand were first synthesized. The antenna effect of the ligand on Tb(III) green luminescence and the presence of water molecules in the coordination sphere of Gd(III) bring strong luminescent and magnetic performance to the core-shell nanoparticles. The size and the core-shell morphology of the colloids were studied using transmission electron microscopy and dynamic light scattering. The correlation between photophysical and magnetic properties of the nanoparticles and their core composition was highlighted. The core composition was optimized for the longitudinal relaxivity to be greater than that of the commercial magnetic resonance imaging (MRI) contrast agents together with high level of Tb(III)-centered luminescence. The tuning of both magnetic and luminescent output of nanoparticles is obtained via the simple variation of lanthanide chelates concentrations in the initial synthetic solution. The exposure of the pheochromocytoma 12 (PC 12) tumor cells and periphery human blood lymphocytes to nanoparticles results in negligible effect on cell viability, decreased platelet aggregation and bright coloring, indicating the nanoparticles as promising candidates for dual magneto-fluorescent bioimaging.

[Single and combining effects of Calculus Bovis and zolpidem on inhibitive neurotransmitter of rat striatum corpora].

PubMed

Liu, Ping; He, Xinrong; Guo, Mei

2010-04-01

To investigate the correlation effects between single or combined administration of Calculus Bovis or zolpidem and changes of inhibitive neurotransmitter in rat striatum corpora. Sampling from rat striatum corpora was carried out through microdialysis. The content of two inhibitive neurotransmitters in rat corpus striatum- glycine (Gly) and gama aminobutyric acid (GABA), was determined by HPLC, which involved pre-column derivation with orthophthaladehyde, reversed-phase gradient elution and fluorescence detection. GABA content of rat striatum corpora in Calculus Bovis group was significantly increased compared with saline group (P < 0.01). GABA content of zolpidem group and Calculus Boris plus zolpidem group were increased largely compared with saline group as well (P < 0.05). GABA content of Calculus Bovis group was higher than combination group (P < 0.05). GABA content of zolpidem group was not significantly different from combination group. Gly content of Calculus Bovis or zolpidem group was markedly increased compared with saline group or combination group (P < 0.05). Contents of two inhibitive neurotransmitters in rat striatum corpora were all significantly increased in Calculus Bovis group, zolpidem group and combination group. The magnitude of increase was lower in combination group than in Calculus Bovis group and Zolpidem group, suggesting that Calculus Bovis promoted encephalon inhibition is more powerful than zolpidem. The increase in two inhibitive neurotransmitters did not show reinforcing effect in combination group, suggesting that Calculus Bovis and zolpidem may compete the same receptors. Therefore, combination of Calculus Bovis containing drugs and zolpidem has no clinical significance. Calculus Bovis shouldn't as an aperture-opening drugs be used for resuscitation therapy.

Feedforward somatosensory inhibition is normal in cervical dystonia.

PubMed

Ferrè, Elisa R; Ganos, Christos; Bhatia, Kailash P; Haggard, Patrick

2015-03-01

Insufficient cortical inhibition is a key pathophysiological finding in dystonia. Subliminal sensory stimuli were reported to transiently inhibit somatosensory processing. Here we investigated whether such subliminal feedforward inhibition is reduced in patients with cervical dystonia. Sixteen cervical dystonia patients and 16 matched healthy controls performed a somatosensory detection task. We measured the drop in sensitivity to detect a threshold-level digital nerve shock when it was preceded by a subliminal conditioning shock, compared to when it was not. Subliminal conditioning shocks reduced sensitivity to threshold stimuli to a similar extent in both patients and controls, suggesting that somatosensory subliminal feedforward inhibition is normal in cervical dystonia. Somatosensory feedforward inhibition was normal in this group of cervical dystonia patients. Our results qualify previous concepts of a general dystonic deficit in sensorimotor inhibitory processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fate of tenogenic differentiation potential of human bone marrow stromal cells by uniaxial stretching affected by stretch-activated calcium channel agonist gadolinium

PubMed Central

Balaji Raghavendran, Hanumantha Rao; Pingguan-Murphy, Belinda; Abbas, Azlina A.; Merican, Azhar M.; Kamarul, Tunku

2017-01-01

The role for mechanical stimulation in the control of cell fate has been previously proposed, suggesting that there may be a role of mechanical conditioning in directing mesenchymal stromal cells (MSCs) towards specific lineage for tissue engineering applications. Although previous studies have reported that calcium signalling is involved in regulating many cellular processes in many cell types, its role in managing cellular responses to tensile loading (mechanotransduction) of MSCs has not been fully elucidated. In order to establish this, we disrupted calcium signalling by blocking stretch-activated calcium channel (SACC) in human MSCs (hMSCs) in vitro. Passaged-2 hMSCs were exposed to cyclic tensile loading (1 Hz + 8% for 6, 24, 48, and 72 hours) in the presence of the SACC blocker, gadolinium. Analyses include image observations of immunochemistry and immunofluorescence staining from extracellular matrix (ECM) production, and measuring related tenogenic and apoptosis gene marker expression. Uniaxial tensile loading increased the expression of tenogenic markers and ECM production. However, exposure to strain in the presence of 20 μM gadolinium reduced the induction of almost all tenogenic markers and ECM staining, suggesting that SACC acts as a mechanosensor in strain-induced hMSC tenogenic differentiation process. Although cell death was observed in prolonged stretching, it did not appear to be apoptosis mediated. In conclusion, the knowledge gained in this study by elucidating the role of calcium in MSC mechanotransduction processes, and that in prolonged stretching results in non-apoptosis mediated cell death may be potential useful for regenerative medicine applications. PMID:28654695

Usefulness of the dynamic gadolinium-enhanced magnetic resonance imaging with simultaneous acquisition of coronal and sagittal planes for detection of pituitary microadenomas.

PubMed

Lee, Han Bee; Kim, Sung Tae; Kim, Hyung-Jin; Kim, Keon Ha; Jeon, Pyoung; Byun, Hong Sik; Choi, Jin Wook

2012-03-01

Does dynamic gadolinium-enhanced imaging with simultaneous acquisition of coronal and sagittal planes improve diagnostic accuracy of pituitary microadenomas compared with coronal images alone? Fifty-six patients underwent 3-T sella MRI including dynamic simultaneous acquisition of coronal and sagittal planes after gadolinium injection. According to conspicuity, lesions were divided into four scores (0, no; 1, possible; 2, probable; 3, definite delayed enhancing lesion). Additional information on supplementary sagittal images compared with coronal ones was evaluated with a 4-point score (0, no; 1, possible; 2, probable; 3, definite additional information). Accuracy of tumour detection was calculated. Average scores for lesion detection of a combination of two planes, coronal, and sagittal images were 2.59, 2.32, and 2.18. 6/10 lesions negative on coronal images were detected on sagittal ones. Accuracy of a combination of two planes, of coronal and of sagittal images was 92.86%, 82.14% and 75%. Six patients had probable or definite additional information on supplementary sagittal images compared with coronal ones alone (10.71%). Dynamic MRI with combined coronal and sagittal planes was more accurate for detection of pituitary microadenomas than routinely used coronal images. Simultaneous dynamic enhanced acquisition can make study time fast and costs low. We present a new dynamic MRI technique for evaluating pituitary microadenomas • This technique provides simultaneous acquisition of contrast enhanced coronal and sagittal images. • This technique makes the diagnosis more accurate and reduces the examination time. • Such MR imaging only requires one single bolus of contrast agent.

High spatial resolution free-breathing 3D late gadolinium enhancement cardiac magnetic resonance imaging in ischaemic and non-ischaemic cardiomyopathy: quantitative assessment of scar mass and image quality.

PubMed

Bizino, Maurice B; Tao, Qian; Amersfoort, Jacob; Siebelink, Hans-Marc J; van den Bogaard, Pieter J; van der Geest, Rob J; Lamb, Hildo J

2018-04-06

To compare breath-hold (BH) with navigated free-breathing (FB) 3D late gadolinium enhancement cardiac MRI (LGE-CMR) MATERIALS AND METHODS: Fifty-one patients were retrospectively included (34 ischaemic cardiomyopathy, 14 non-ischaemic cardiomyopathy, three discarded). BH and FB 3D phase sensitive inversion recovery sequences were performed at 3T. FB datasets were reformatted into normal resolution (FB-NR, 1.46x1.46x10mm) and high resolution (FB-HR, isotropic 0.91-mm voxels). Scar mass, scar edge sharpness (SES), SNR and CNR were compared using paired-samples t-test, Pearson correlation and Bland-Altman analysis. Scar mass was similar in BH and FB-NR (mean ± SD: 15.5±18.0 g vs. 15.5±16.9 g, p=0.997), with good correlation (r=0.953), and no bias (mean difference ± SD: 0.00±5.47 g). FB-NR significantly overestimated scar mass compared with FB-HR (15.5±16.9 g vs 14.4±15.6 g; p=0.007). FB-NR and FB-HR correlated well (r=0.988), but Bland-Altman demonstrated systematic bias (1.15±2.84 g). SES was similar in BH and FB-NR (p=0.947), but significantly higher in FB-HR than FB-NR (p<0.01). SNR and CNR were lower in BH than FB-NR (p<0.01), and lower in FB-HR than FB-NR (p<0.01). Navigated free-breathing 3D LGE-CMR allows reliable scar mass quantification comparable to breath-hold. During free-breathing, spatial resolution can be increased resulting in improved sharpness and reduced scar mass. • Navigated free-breathing 3D late gadolinium enhancement is reliable for myocardial scar quantification. • High-resolution 3D late gadolinium enhancement increases scar sharpness • Ischaemic and non-ischaemic cardiomyopathy patients can be imaged using free-breathing LGE CMR.

[Comparing the activity of multiple sclerosis (MS) at the minute and at 20 minutes of gadolinium application in magnetic resonance imaging (MRI) of the brain?

PubMed

Saldívar-Uribe, Christina; de la Portilla-Villanueva, Mario Alberto; Esau-Mendoza-García, Alberto

2017-01-01

The aim was to compare active disease in patients diagnosed with multiple sclerosis, brain by MRI after gadolinium application at one minute and 20 minutes. A longitudinal, prospective, observational, analytical and comparative study was conducted in 18 patients over 18 years of age diagnosed with multiple sclerosis (MS). An analysis was made for each patient, watching for inflammatory activity in MS lesions, comparing the results to one minute and 20 minutes after the application of gadolinium. For the descriptive analysis, absolute frequencies and percentages were used, as well as means and standard deviations or medians with ranges for the inferential analysis comparing the presence or absence of enhancement in lesions at one minute and 20 minutes; the exact probability test used was Fisher. Finally, the results were analyzed, looking at the gender distribution: 14 (77.8%) were female. The average age was 36.2 ± 9.5 years, with a minimum age of 18 years and a maximum of 55 years; four patients (22.2%) presented further highlight active lesions at 20 minutes, and two patients (11.1%) presented enhancement at one minute. Concluding that MRI in the diagnosis of MS is very important for the detection of activity in lesions caused by the disease, it is evident that the optimum time for evaluation of postcontrast sequences is 20 minutes.

Angiotensin-converting enzyme and matrix metalloproteinase inhibition with developing heart failure: comparative effects on left ventricular function and geometry

NASA Technical Reports Server (NTRS)

McElmurray, J. H. 3rd; Mukherjee, R.; New, R. B.; Sampson, A. C.; King, M. K.; Hendrick, J. W.; Goldberg, A.; Peterson, T. J.; Hallak, H.; Zile, M. R.;

Biological effects of RNAi targeted inhibiting Tiam1 gene expression on cholangiocarcinoma cells.

PubMed

Cheng, Wei; Liu, Yaling; Zuo, Zhi; Yin, Xinmin; Jiang, Bo; Chen, Daojin; Peng, Chuang; Yang, Jianhui

2015-01-01

To investigate the characteristics of Tiam1 gene expression in human cholangiocarcinoma tissues and benign bile duct tissues, and to analyze the correlations between Tiam1 gene expression and the degree of tumor differentiation, invasive and metastatic abilities. To explore the effect of targeted inhibiting Tiam1 gene expression on proliferation and migration activity of human cholangiocarcinoma cells. Expression of Tiam1 in 83 cases of cholangiocarcinoma tissues and 25 cases of benign bile tissues was detected using immunohistochemistry. The clinical data of patients with cholangiocarcinoma were collected. The correlations between Tiam1 gene expression and the clinicopathologic features in patients with cholangiocarcinoma were analyzed. The human cholangiocarcinoma RBE cells were divided into 3 groups. Cells in experimental group and control group were respectively transfected with Tiam1 shRNA lentiviral vectors and negative shRNA lentiviral control vectors. Cells in blank group received no treatment. Real-time PCR endogenesis was used to verify Tiam1 gene expression. Cell cycle experiments and MTT assay were used to measure cell proliferation activity. Transwell test was used to detect cell migration activity. The negative rate Tiam1 protein expression in cholangiocarcinoma tissues was significantly higher than that in benign bile tissues (P<0.001). Tiam1 protein expression in cholangiocarcinoma tissues had correlations with cholangiocarcinoma differentiation degree, TNM stage and lymph node metastasis (P<0.05), and had no significant correlations with gender, age and distant metastasis (P>0.05). Real-time PCR detection indicated that Tiam1 expression of experimental group was significantly lower than that in control group and blank group (P<0.05), demonstrating that Tiam1 shRNA was effective on Tiam1 gene silencing in RBE cells. Cell cycle experiment showed that the percentage of S phase in cell cycle in experimental group was lower than that in control group

Biological effects of RNAi targeted inhibiting Tiam1 gene expression on cholangiocarcinoma cells

PubMed Central

Cheng, Wei; Liu, Yaling; Zuo, Zhi; Yin, Xinmin; Jiang, Bo; Chen, Daojin; Peng, Chuang; Yang, Jianhui

2015-01-01

Objective: To investigate the characteristics of Tiam1 gene expression in human cholangiocarcinoma tissues and benign bile duct tissues, and to analyze the correlations between Tiam1 gene expression and the degree of tumor differentiation, invasive and metastatic abilities. To explore the effect of targeted inhibiting Tiam1 gene expression on proliferation and migration activity of human cholangiocarcinoma cells. Methods: Expression of Tiam1 in 83 cases of cholangiocarcinoma tissues and 25 cases of benign bile tissues was detected using immunohistochemistry. The clinical data of patients with cholangiocarcinoma were collected. The correlations between Tiam1 gene expression and the clinicopathologic features in patients with cholangiocarcinoma were analyzed. The human cholangiocarcinoma RBE cells were divided into 3 groups. Cells in experimental group and control group were respectively transfected with Tiam1 shRNA lentiviral vectors and negative shRNA lentiviral control vectors. Cells in blank group received no treatment. Real-time PCR endogenesis was used to verify Tiam1 gene expression. Cell cycle experiments and MTT assay were used to measure cell proliferation activity. Transwell test was used to detect cell migration activity. Results: The negative rate Tiam1 protein expression in cholangiocarcinoma tissues was significantly higher than that in benign bile tissues (P<0.001). Tiam1 protein expression in cholangiocarcinoma tissues had correlations with cholangiocarcinoma differentiation degree, TNM stage and lymph node metastasis (P<0.05), and had no significant correlations with gender, age and distant metastasis (P>0.05). Real-time PCR detection indicated that Tiam1 expression of experimental group was significantly lower than that in control group and blank group (P<0.05), demonstrating that Tiam1 shRNA was effective on Tiam1 gene silencing in RBE cells. Cell cycle experiment showed that the percentage of S phase in cell cycle in experimental group was lower

Ultra high molecular weight polyethylene (UHMWPE) fiber epoxy composite hybridized with Gadolinium and Boron nanoparticles for radiation shielding

NASA Astrophysics Data System (ADS)

Mani, Venkat; Prasad, Narasimha S.; Kelkar, Ajit

2016-09-01

Deep space radiations pose a major threat to the astronauts and their spacecraft during long duration space exploration missions. The two sources of radiation that are of concern are the galactic cosmic radiation (GCR) and the short lived secondary neutron radiations that are generated as a result of fragmentation that occurs when GCR strikes target nuclei in a spacecraft. Energy loss, during the interaction of GCR and the shielding material, increases with the charge to mass ratio of the shielding material. Hydrogen with no neutron in its nucleus has the highest charge to mass ratio and is the element which is the most effective shield against GCR. Some of the polymers because of their higher hydrogen content also serve as radiation shield materials. Ultra High Molecular Weight Polyethylene (UHMWPE) fibers, apart from possessing radiation shielding properties by the virtue of the high hydrogen content, are known for extraordinary properties. An effective radiation shielding material is the one that will offer protection from GCR and impede the secondary neutron radiations resulting from the fragmentation process. Neutrons, which result from fragmentation, do not respond to the Coulombic interaction that shield against GCR. To prevent the deleterious effects of secondary neutrons, targets such as Gadolinium are required. In this paper, the radiation shielding studies that were carried out on the fabricated sandwich panels by vacuum-assisted resin transfer molding (VARTM) process are presented. VARTM is a manufacturing process used for making large composite structures by infusing resin into base materials formed with woven fabric or fiber using vacuum pressure. Using the VARTM process, the hybridization of Epoxy/UHMWPE composites with Gadolinium nanoparticles, Boron, and Boron carbide nanoparticles in the form of sandwich panels were successfully carried out. The preliminary results from neutron radiation tests show that greater than 99% shielding performance was

Response inhibition under alcohol: effects of cognitive and motivational conflict.

PubMed

Fillmore, M T; Vogel-Sprott, M

2000-03-01

This experiment tested the effect of cognitive and motivational conflict on response inhibition under alcohol. Fifty-six male social drinkers were randomly assigned to one of eight groups (n = 8). Four pairs of groups received 0.62 g/kg of alcohol, or a placebo, and each pair performed a go/stop choice reaction time task under one of four conflict conditions. One condition (C) produced cognitive conflict by presenting "go" and "stop" signals in the task. Another condition (IR) added motivational conflict by administering an equal monetary reward for inhibiting responses to stop-signals, and for responding to go-signals. The remaining two conditions resolved the motivational conflict by administering the monetary reward only for inhibitions (I), or only for responses (R). Compared with placebo, alcohol reduced inhibitions (i.e., impaired inhibitory control) under cognitive conflict (C; p = .041) and under motivational conflict (IR; p = .012). No significant effect of alcohol on inhibitions was observed in conditions where conflict was resolved (i.e., I and R). The study shows that alcohol can reduce the ability to inhibit a response. However, impaired inhibitory control is not an inevitable outcome of the drug action, because it can be counteracted by the consequences of behavior in the situation.

A Manganese Alternative to Gadolinium for MRI Contrast

PubMed Central

Gale, Eric M.; Atanasova, Iliyana P.; Blasi, Francesco; Ay, Ilknur; Caravan, Peter

2016-01-01

Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) are routinely used to diagnose soft tissue and vascular abnormalities. However safety concerns limit the use of iodinated and gadolinium- (Gd) based CT and MRI contrast media in renally compromised patients. With an estimated 14% of the US population suffering from chronic kidney disease (CKD), contrast media compatible with renal impairment is sorely needed. We present the new manganese(II) complex [Mn(PyC3A)(H2O)]- as a Gd alternative. [Mn(PyC3A)(H2O)]- is amongst the most stable Mn(II) complexes at pH 7.4 (log KML = 11.40). In the presence of 25 mol equiv. Zn at pH 6.0, 37 °C, [Mn(PyC3A)(H2O)]- is 20-fold more resistant to dissociation than [Gd(DTPA)(H2O)]2-. Relaxivity of [Mn(PyC3A)(H2O)]- in blood plasma is comparable to commercial Gd contrast agents. Biodistribution analysis confirms that [Mn(PyC3A)(H2O)]- clears via a mixed renal/ hepatobiliary pathway with >99% elimination by 24h. [Mn(PyC3A)(H2O)]- was modified to form a bifunctional chelator and 4 chelates were conjugated to a fibrin-specific peptide to give Mn-FBP. Mn-FBP binds the soluble fibrin fragment DD(E) with Kd = 110 nM. Per Mn relaxivity of Mn-FBP is 4-fold greater than [Mn(PyC3A)(H2O)]- and increases 60% in the presence of fibrin, consistent with binding. Mn-FBP provided equivalent thrombus enhancement to the state of the art Gd analog, EP-2104R, in a rat model of arterial thrombosis. Mn metabolite analysis reveals no evidence of dechelation and the probe was >99% eliminated after 24 hr. [Mn(PyC3A)(H2O)]- is a lead development candidate for an imaging probe that is compatible with renally compromised patients. PMID:26588204

Layered gadolinium hydroxides for simultaneous drug delivery and imaging.

PubMed

Xu, Yadong; Goyanes, Alvaro; Wang, Yuwei; Weston, Andrew J; So, Po-Wah; Geraldes, Carlos F G C; Fogg, Andrew M; Basit, Abdul W; Williams, Gareth R

2018-02-27

The potential of the layered gadolinium hydroxide (LGdH) [Gd 2 (OH) 5 ]Cl·yH 2 O (LGdH-Cl) for simultaneous drug delivery and magnetic resonance imaging was explored in this work. Three non-steroidal anti-inflammatory drugs (diclofenac [dic], ibuprofen [ibu], and naproxen [nap]) were intercalated into LGdH-Cl for the first time, using three different routes (ion exchange intercalation, coprecipitation, and exfoliation-self-assembly). X-ray diffraction, elemental microanalysis and IR spectroscopy confirmed successful incorporation of the drug into the interlayer spaces of the LGdH in all cases. From a comparison of the guest anion sizes and interlayer spacings, the active ingredients are believed to adopt intertwined bilayer configurations between the LGdH layers. The materials prepared by coprecipitation in general have noticeably higher drug loadings than those produced by ion exchange or self-assembly, as a result of the incorporation of some neutral drug into the composites. The LGdH-drug intercalates are stable at neutral pH, but rapidly degrade in acidic conditions to free Gd 3+ into solution. While LGdH-nap releases its drug loading into solution very rapidly (within ca. 1.5 h) at pH 7.4, LGdH-dic shows sustained release over 4 h, and LGdH-ibu extends this to 24 h. The latter composites therefore can be incorporated into enteric-coated tablets to provide sustained release in the small intestine. The drug intercalates are highly biocompatible and retain the proton relaxivity properties of the parent LGdH-Cl, with the materials most promising for use as negative contrast agents in MRI. Overall, the LGdH-drug intercalation compounds appear to have great potential for use in theranostic applications.

A new method for the determination of Gadolinium in ppq levels

NASA Astrophysics Data System (ADS)

Brünjes, Robert; Bichler, Andrea; Hofmann, Thilo

2015-04-01

The use of Gadolinium (Gd) complexes as a contrast agent in Magnetic Resonance Imaging (MRI) results in an enhanced Gd input in the aquatic environment. Gd-complexes are excreted by humans unmetabolized within 12h after application. Passing the sewage systems with almost no degradation taking place, they successively reach surface waters, which make Gd a capable tracer for surface water/groundwater (SW/GW) interactions. The natural background concentration of Gd and other rare earth elements (REE) occur at ultratrace levels [low ng/L]. Crust-normalized REE patterns show positive Gd-anomalies in surface water, groundwater, and recently also in tap water. The difference between the total concentration and its natural background concentration estimated by the REE pattern is the anthropogenic Gd. Not only densely populated areas are affected by the presence of anthropogenic Gd. Studies have shown that even in rural areas without MRI facilities, anthropogenic Gd can be detected, since people are sent home after treatment. However, low input concentrations and mixing with natural waters lead to a decrease of Gd concentration below the current limit of quantification (LOQ) [1-5ng/L]. Often anthropogenic Gd cannot be calculated, although it is present, because natural background concentration cannot be determined with current methods, in particular in areas with low waste water load (e.g. headwater catchments). A new method using an on-line preconcentration system "SeaFAST" (Elemental Scientific Inc., USA), in combination with a desolvation system "Apex Q" (Elemental Scientific Inc., USA) and a QQQ-ICP-MS instrument (Agilent Technologies, Japan) does lower the LOQ for REE by a factor of 10 to 20. The SeaFAST-system uses a resin with ethylenediaminetriacetic acid and iminodiacetic acid functional groups to preconcentrate specifically REE as they are exclusively trivalent while anions, alkali and alkaline earth cations are washed out. The Apex Q interface is also supposed to

Alterations in neural systems mediating cognitive flexibility and inhibition in mood disorders.

PubMed

Piguet, Camille; Cojan, Yann; Sterpenich, Virginie; Desseilles, Martin; Bertschy, Gilles; Vuilleumier, Patrik

2016-04-01

Impairment in mental flexibility may be a key component contributing to cardinal cognitive symptoms among mood disorders patients, particularly thought control disorders. Impaired ability to switch from one thought to another might reflect difficulties in either generating new mental states, inhibiting previous states, or both. However, the neural underpinnings of impaired cognitive flexibility in mood disorders remain largely unresolved. We compared a group of mood disorders patients (n = 29) and a group of matched healthy subjects (n = 32) on a novel task-switching paradigm involving happy and sad faces, that allowed us to separate generation of a new mental set (Switch Cost) and inhibition of the previous set during switching (Inhibition Cost), using fMRI. Behavioral data showed a larger Switch Cost in patients relative to controls, but the average Inhibition Cost did not differ between groups. At the neural level, a main effect of group was found with stronger activation of the subgenual cingulate cortex in patients. The larger Switch Cost in patients was reflected by a stronger recruitment of brain regions involved in attention and executive control, including the left intraparietal sulcus, precuneus, left inferior fontal gyrus, and right anterior cingulate. Critically, activity in the subgenual cingulate cortex was not downregulated by inhibition in patients relative to controls. In conclusion, mood disorder patients have exaggerated Switch Cost relative to controls, and this deficit in cognitive flexibility is associated with increased activation of the fronto-parietal attention networks, combined with impaired modulation of the subgenual cingulate cortex when inhibition of previous mental states is needed. © 2016 Wiley Periodicals, Inc.

Determination of trace level thorium and uranium in high purity gadolinium sulfate using ICP-MS with solid-phase chromatographic extraction resins

NASA Astrophysics Data System (ADS)

Ito, S.; Takaku, Y.; Ikeda, M.; Kishimoto, Y.

2018-01-01

The Super Kamiokand-Gadolinium (SK-Gd) project is the upgrade of the Super-Kamiokande (SK) detector in order to discover Supernova Relic Neutrinos (SRNs) by loading 0.2% of Gd2(SO4)3 into a 50 kton of the SK water tank. In order to continue solar neutrino measurement with low energy threshold at ˜3.5 MeV, main radioactive contamination, U and Th in Gd2(SO4)3, should be purified before loading. We developed solid-phase extraction technique to measure low concentration of U and Th in Gd2(SO4)3 by ICP-MS. The extraction technique and current status will be presented.

Spectral presaturation inversion recovery MR imaging sequence after gadolinium injection to differentiate fibrotic scar tissue and neoplastic strands in the mesorectal fat in patients undergoing restaging of rectal carcinoma after neoadjuvant chemo- and radiation therapy.

PubMed

Quaia, Emilio; Ulcigrai, Veronica; Coss, Matteo; De Paoli, Luca; Ukmar, Maja; Zanconati, Fabrizio; De Pellegrin, Alessandro; De Manzini, Nicolò; Cova, Maria Assunta

2011-11-01

To retrospectively assess the value of spectral presaturation by inversion-recovery (SPIR) magnetic resonance (MR) imaging sequence after gadolinium injection to differentiate fibrotic scar tissue and tumoral infiltration within the mesorectal fat in patients with rectal carcinoma undergoing MR restaging after neoadjuvant chemo- and radiation therapy (CRT). Forty-three consecutive patients (mean age, 65.8 years; range, 46-85 years; male:female, 29:14) with locally advanced rectal carcinoma underwent CRT followed by surgery. MR imaging was performed before and after completion of CRT by using T2-weighted turbo spin-echo and T1-weighted SPIR sequences before and after gadolinium injection, and MR images were assessed by two radiologists in consensus. Logistic regression was conducted to test the significance of the MR image findings with histology. After CRT the disease was either limited to the rectal wall (n = 18 patients) or presented perirectal infiltration (n = 25) on histology. In 21 patients, mesorectal enhancing strands were observed. Reticular-shaped enhancing strands reaching the mesorectal fascia presented the highest correlation with tumor infiltration of the mesorectal fat (OR 130.33, 95% CI: 4.1-4220.29; logistic regression), whereas linear-shaped enhancing strands either reaching or not reaching the mesorectal fascia (OR 0.25 or 0.1, 95% CI: 0.024-2.6 or 0.01-1.07) revealed the lowest correlation. Reticular-shaped enhancing strands on SPIR MR imaging after gadolinium injection are associated with tumor infiltration of the mesorectal fat. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

Effect of Different Administration Paradigms on Cholinesterase Inhibition following Repeated Chlorpyrifos Exposure in Late Preweanling Rats

PubMed Central

Carr, Russell L.; Nail, Carole A.

2008-01-01

Chlorpyrifos (CPS) is widely used in agricultural settings and residue analysis has suggested that children in agricultural communities are at risk of exposure. This has resulted in a large amount of literature investigating the potential for CPS-induced developmental neurotoxic effects. Two developmental routes of administration of CPS are orally in corn oil at a rate of 0.5 ml/kg and subcutaneously in dimethyl sulfoxide (DMSO) at a rate of 1.0 ml/kg. For comparison between these methods, rat pups were exposed daily from days 10 to 16 to CPS (5 mg/kg) either orally dissolved in corn oil or subcutaneously dissolved in DMSO, both at rates of either 0.5 or 1.0 ml/kg. A representative vehicle/route group was present for each treatment. Both the low and high volume CPS in DMSO subcutaneous groups were lower than that of the low and high volume CPS in oil oral groups. At 4 h following the final administration, serum carboxylesterase was inhibited > 90% with all treatments. For cholinesterase activity in the cerebellum, medulla-pons, forebrain, and hindbrain, and serum, inhibition in the CPS-oil groups was similar and inhibition in the CPS-DMSO groups was similar. However, significantly greater inhibition was present in the high volume CPS-DMSO group as compared to the CPS-oil groups. Inhibition in the low volume CPS-DMSO group was generally between that in the CPS-oil groups and the high volume CPS-DMSO group. These data suggest that using DMSO as a vehicle for CPS may alter the level of brain ChE inhibition. PMID:18703558

Gadolinium-encapsulating iron oxide nanoprobe as activatable NMR/MRI contrast agent.

PubMed

Santra, Santimukul; Jativa, Samuel D; Kaittanis, Charalambos; Normand, Guillaume; Grimm, Jan; Perez, J Manuel

2012-08-28

Herein we report a novel gadolinium-encapsulating iron oxide nanoparticle-based activatable NMR/MRI nanoprobe. In our design, Gd-DTPA is encapsulated within the poly(acrylic acid) (PAA) polymer coating of a superparamagnetic iron oxide nanoparticle (IO-PAA), yielding a composite magnetic nanoprobe (IO-PAA-Gd-DTPA) with quenched longitudinal spin-lattice magnetic relaxation (T(1)). Upon release of the Gd-DTPA complex from the nanoprobe's polymeric coating in acidic media, an increase in the T(1) relaxation rate (1/T(1)) of the composite magnetic nanoprobe was observed, indicating a dequenching of the nanoprobe with a corresponding increase in the T(1)-weighted MRI signal. When a folate-conjugated nanoprobe was incubated in HeLa cells, a cancer cell line overexpressing folate receptors, an increase in the 1/T(1) signal was observed. This result suggests that, upon receptor-mediated internalization, the composite magnetic nanoprobe degraded within the cell's lysosome acidic (pH 5.0) environment, resulting in an intracellular release of Gd-DTPA complex with subsequent T(1) activation. In addition, when an anticancer drug (Taxol) was coencapsulated with the Gd-DTPA within the folate receptor targeting composite magnetic nanoprobe, the T(1) activation of the probe coincided with the rate of drug release and corresponding cytotoxic effect in cell culture studies. Taken together, these results suggest that our activatable T(1) nanoagent could be of great importance for the detection of acidic tumors and assessment of drug targeting and release by MRI.

Synthesis of gadolinium carbonate-conjugated-poly(ethylene)glycol (Gd{sub 2}(CO{sub 3}){sub 3}@PEG) particles via a modified solvothermal method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nasution, Erika L. Y.; Ahab, Atika; Nuryadin, Bebeh W.

2016-02-08

PEGylated gadolinium carbonate ((Gd{sub 2}(CO{sub 3}){sub 3})@PEG) powder was successfully synthesized by a modified solvothermal method. The synthesized products were characterized by means of X-ray diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Energy Dispersive X-ray Spectroscopy (EDS). A systematic change in the chemical surface composition, crystallinity and size properties of the Gd{sub 2}(CO{sub 3}){sub 3}@PEG particles was observed by increasing the reaction time at 5 hours, 7 hours, and 8 hours. The corresponding XRD patterns showed that the Gd{sub 2}(CO{sub 3}){sub 3} particles had hexagonal symmetry (JCPDS No. 37-0559) with a crystallite size of 3.5,more » 2.9, and 4.6 nm. FTIR spectra showed that the Gd{sub 2}(CO{sub 3}){sub 3})@PEG particles were formed with the PEG as carbonyl and hydroxyl group attached to the surface. SEM analysis showed that the Gd{sub 2}(CO{sub 3}){sub 3})@PEG particles had a flake-like morphology of homogeneous sized particles and agglomerates. EDS analysis confirmed the presence of constituent Gd{sub 2}(CO{sub 3}){sub 3} elements.« less

Neural correlates of response inhibition in current and former smokers.

PubMed

Weywadt, Christina R; Kiehl, Kent A; Claus, Eric D

2017-02-15

Loss of behavioral control is a hallmark of addiction. Individual differences in basic cognitive processes such as response inhibition may be important for interrupting automatic behaviors associated with smoking and supporting prolonged abstinence. To examine how response inhibition and error monitoring processes differ as a function of smoking status, current smokers, former smokers and never smokers (N=126) completed a simple Go/No-Go task while undergoing functional magnetic resonance imaging. All groups performed similarly on the task and similarly engaged the inferior frontal gyrus and dorsal anterior cingulate cortex, regions traditionally associated with response inhibition and error monitoring, respectively. During response inhibition (i.e., Correct Rejects>Hits contrast), overall group differences emerged in the recruitment of the cerebellum, while individual group differences in error monitoring (False Alarms>Hits contrast) were seen for regions of the parietal lobe and thalamus (current smokers>former smokers), as well as regions of the bilateral cerebellum, parahippocampal gyrus and superior parietal lobe (i.e., ever smokers>never smokers). We discuss how our results replicate two previous large-sample studies that used the same Go/No-Go task and review these data in terms of network models of inhibitory and error monitoring abnormalities in addiction. Copyright © 2016 Elsevier B.V. All rights reserved.

Association of tellurium resistance and bacteriophage inhibition conferred by R plasmids.

PubMed Central

Taylor, D E; Summers, A O

1979-01-01

Concomitant resistance to tellurium compounds (Ter) and inhibition of coli-phage development (Phi) are properties mediated by many H2 incompatibility group R plasmids which have been isolated from diverse bacterial and geographic sources. Ter plasmids from tellurium-resistant bacteria that were isolated from sewage and industrial wastes also mediated phage inhibition. Of these Ter plasmids, three from Citrobacter freundii belonged to the H incompatibility group, whereas three from Klebsiella pneumoniae did not. Images PMID:374351

Inhibition Plasticity in Older Adults: Practice and Transfer Effects Using a Multiple Task Approach.

PubMed

Wilkinson, Andrea J; Yang, Lixia

2016-01-01

OBJECTIVE. To examine plasticity of inhibition, as indexed by practice effects of inhibition tasks and the associated transfer effects, using a multiple task approach in healthy older adults. METHOD. Forty-eight healthy older adults were evenly assigned to either a practice group or a no-contact control group. All participants completed pretest (2.5 hours) and posttest (2 hours) sessions, with a 2-week interval in between. During the 2-week interval, only the practice group completed six 30-minute practice sessions (three sessions per week for two consecutive weeks) of three lab-based inhibition tasks. RESULTS. All three inhibition tasks demonstrated significant improvement across practice sessions, suggesting practice-induced plasticity. The benefit, however, only transferred to near-near tasks. The results are inconclusive with regard to the near-far and far-far transfer effects. DISCUSSION. This study further extends literature on practice effects of inhibition in older adults by using a multiple task approach. Together with previous work, the current study suggests that older adults are able to improve inhibition performance through practice and transfer the practice gains to tasks that overlap in both target cognitive ability and task structure (i.e., near-near tasks).

Inhibition Plasticity in Older Adults: Practice and Transfer Effects Using a Multiple Task Approach

PubMed Central

Wilkinson, Andrea J.; Yang, Lixia

2016-01-01

Objective. To examine plasticity of inhibition, as indexed by practice effects of inhibition tasks and the associated transfer effects, using a multiple task approach in healthy older adults. Method. Forty-eight healthy older adults were evenly assigned to either a practice group or a no-contact control group. All participants completed pretest (2.5 hours) and posttest (2 hours) sessions, with a 2-week interval in between. During the 2-week interval, only the practice group completed six 30-minute practice sessions (three sessions per week for two consecutive weeks) of three lab-based inhibition tasks. Results. All three inhibition tasks demonstrated significant improvement across practice sessions, suggesting practice-induced plasticity. The benefit, however, only transferred to near-near tasks. The results are inconclusive with regard to the near-far and far-far transfer effects. Discussion. This study further extends literature on practice effects of inhibition in older adults by using a multiple task approach. Together with previous work, the current study suggests that older adults are able to improve inhibition performance through practice and transfer the practice gains to tasks that overlap in both target cognitive ability and task structure (i.e., near-near tasks). PMID:26885407

An albumin-based theranostic nano-agent for dual-modal imaging guided photothermal therapy to inhibit lymphatic metastasis of cancer post surgery.

PubMed

Chen, Qian; Liang, Chao; Wang, Xin; He, Jingkang; Li, Yonggang; Liu, Zhuang

2014-11-01

A large variety of cancers are associated with a high incidence of lymph node metastasis, which leads to a high risk of cancer death. Herein, we demonstrate that multimodal imaging guided photothermal therapy can inhibit tumor metastasis after surgery by burning the sentinel lymph nodes (SLNs) with metastatic tumor cells. A near-infrared dye, IR825, is absorbed onto human serum albumin (HSA), which is covalently linked with diethylenetriamine pentaacetic acid (DTPA) molecules to chelate gadolinium. The formed HSA-Gd-IR825 nanocomplex exhibits strong fluorescence together with high near-infrared (NIR) absorbance, and in the mean time could serve as a T1 contrast agent in magnetic resonance (MR) imaging. In vivo bi-modal fluorescence and MR imaging uncovers that HSA-Gd-IR825 after being injected into the primary tumor would quickly migrate into tumor-associated SLNs through lymphatic circulation. Utilizing the strong NIR absorbance of HSA-Gd-IR825, SLNs with metastatic cancer cells can be effectively ablated under exposure to a NIR laser. Such treatment when combined with surgery to remove the primary tumor offers remarkable therapeutic outcomes in greatly inhibiting further metastatic spread of cancer cells and prolonging animal survival. Our work presents an albumin-based theranostic nano-probe with functions of multimodal imaging and photothermal therapy, together with a 'photothermal ablation assisted surgery' strategy, promising for future clinical cancer treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Caustic Precipitation of Plutonium and Uranium with Gadolinium as a Neutron Poison

DOE Office of Scientific and Technical Information (OSTI.GOV)

VISSER, ANN E.; BRONIKOWSKI, MICHAEL G.; RUDISILL, TRACY S.

2005-10-18

The caustic precipitation of plutonium (Pu) and uranium (U) from Pu and U-containing waste solutions has been investigated to determine whether gadolinium (Gd) could be used as a neutron poison for precipitation with greater than a fissile mass containing both Pu and enriched U. Precipitation experiments were performed using both process solution samples and simulant solutions with a range of 2.6-5.16 g/L U and 0-4.3:1 U:Pu. Analyses were performed on solutions at intermediate pH to determine the partitioning of elements for accident scenarios. When both Pu and U were present in the solution, precipitation began at pH 4.5 and bymore » pH 7, 99% of Pu and U had precipitated. When complete neutralization was achieved at pH > 14 with 1.2 M excess OH{sup -}, greater than 99% of Pu, U, and Gd had precipitated. At pH > 14, the particles sizes were larger and the distribution was a single mode. The ratio of hydrogen:fissile atoms in the precipitate was determined after both settling and centrifuging and indicates that sufficient water was associated with the precipitates to provide the needed neutron moderation for Gd to prevent a criticality in solutions containing up to 4.3:1 U:Pu and up to 5.16 g/L U.« less

Random lasing in Nd{sup 3+} doped potassium gadolinium tungstate crystal powder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moura, André L., E-mail: andre.moura@fis.ufal.br; Departamento de Física, Universidade Federal de Pernambuco, 50670-901 Recife, PE; Fewo, Serge I.

2015-02-28

Random laser (RL) emission in Nd{sup 3+} doped potassium gadolinium tungstate—KGd(WO{sub 4}){sub 2}:Nd{sup 3+}—crystal powder is demonstrated. The powder was excited at 813 nm in resonance with the Nd{sup 3+} transition {sup 4}I{sub 9/2}→{sup 4}F{sub 5/2}. RL emission at 1067 nm due to the {sup 4}F{sub 3/2}→{sup 4}I{sub 11/2} transition was observed and characterized. An intensity threshold dependent on the laser spot area and bandwidth narrowing from ≈2.20 nm to ≈0.40 nm were observed and measured. For a beam spot area of 0.4 mm{sup 2}, a RL threshold of 6.5 mJ/mm{sup 2} (90 MW/cm{sup 2}) was determined. For excitation intensity smaller than the RL threshold, only spontaneousmore » emission from level {sup 4}F{sub 3/2} with decay time in the tens microsecond range was observed, but for excitation above the RL threshold, significant shortening of excited level lifetime, characteristic of a stimulated process was found. The overall characteristics measured show that KGd(WO{sub 4}){sub 2}:Nd{sup 3+} is an efficient material for operation of solid state RLs in the near-infrared.« less

Manifestation of intra-atomic 5d6s-4f exchange coupling in photoexcited gadolinium

NASA Astrophysics Data System (ADS)

Zhang, G. P.; Jenkins, T.; Bennett, M.; Bai, Y. H.

2017-12-01

Intra-atomic exchange couplings (IECs) between 5d6s and 4f electrons are ubiquitous in rare-earth metals and play a critical role in spin dynamics. However, detecting them in real time domain has been difficult. Here we show the direct evidence of IEC between 5d6s and 4f electrons in gadolinium. Upon femtosecond laser excitation, 5d6s electrons are directly excited; their majority bands shift toward the Fermi level while their minority bands do the opposite. For the first time, our first-principles minority shift now agrees with the experiment quantitatively. Excited 5d6s electrons lower the exchange potential barrier for 4f electrons, so the 4f states are also shifted in energy, a prediction that can be tested experimentally. Although a significant number of 5d6s electrons, some several eV below the Fermi level, are excited out of the Fermi sea, there is no change in the 4f states, a clear manifestation of intra-atomic exchange coupling.

The impairing effects of mental fatigue on response inhibition: An ERP study

PubMed Central

Guo, Zizheng; Chen, Ruiya; Liu, Xian; Zheng, Yan; Gong, Mingliang; Zhang, Jun

2018-01-01

Mental fatigue is one of the main reasons for the decline of response inhibition. This study aimed to explore the impairing influence of mental fatigue on a driver’s response inhibition. The effects of mental fatigue on response inhibition were assessed by comparing brain activity and behavioral indices when performing a Go/NoGo task before and after a 90-min fatigue manipulation task. Participants in the driving group performed a simulated driving task, while individuals in the control group spent the same time watching movies. We found that participants in the driving group reported higher levels of mental fatigue and had a higher percentage of eye closure and larger lateral deviations from their lane positions, which indicated there was effective manipulation of mental fatigue through a prolonged simulated driving task. After manipulation of mental fatigue, we observed increased reaction time and miss rates, delayed NoGo-N2 latency and Go-P3 latency, and decreased NoGo-P3 amplitude, which indicated that mental fatigue may slow down the speed of the inhibition process, delay the evaluation of visual stimuli and reduce the availability of attentional resources. These findings revealed the underlying neurological mechanisms of how mental fatigue impaired response inhibition. PMID:29856827

Training response inhibition to reduce food consumption: Mechanisms, stimulus specificity and appropriate training protocols.

PubMed

Adams, Rachel C; Lawrence, Natalia S; Verbruggen, Frederick; Chambers, Christopher D

2017-02-01

Training individuals to inhibit their responses towards unhealthy foods has been shown to reduce food intake relative to a control group. Here we aimed to further explore these effects by investigating the role of stimulus devaluation, training protocol, and choice of control group. Restrained eaters received either inhibition or control training using a modified version of either the stop-signal or go/no-go task. Following training we measured implicit attitudes towards food (Study 1) and food consumption (Studies 1 and 2). In Study 1 we used a modified stop-signal training task with increased demands on top-down control (using a tracking procedure and feedback to maintain competition between the stop and go processes). With this task, we found no evidence for an effect of training on implicit attitudes or food consumption, with Bayesian inferential analyses revealing substantial evidence for the null hypothesis. In Study 2 we removed the feedback in the stop-signal training to increase the rate of successful inhibition and revealed a significant effect of both stop-signal and go/no-go training on food intake (compared to double-response and go training, respectively) with a greater difference in consumption in the go/no-go task, compared with the stop-signal task. However, results from an additional passive control group suggest that training effects could be partly caused by increased consumption in the go control group whereas evidence for reduced consumption in the inhibition groups was inconclusive. Our findings therefore support evidence that inhibition training tasks with higher rates of inhibition accuracy are more effective, but prompt caution for interpreting the efficacy of laboratory-based inhibition training as an intervention for behaviour change. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Absence of magnetic ordering and field-induced phase diagram in the gadolinium aluminum garnet

NASA Astrophysics Data System (ADS)

Florea, O.; Lhotel, E.; Jacobsen, H.; Knee, C. S.; Deen, P. P.

2017-12-01

The robustness of spin liquids with respect to small perturbations, and the way magnetic frustration can be lifted by slight changes in the balance between competing magnetic interactions, remains a rich and open issue. We address this question through the study of the gadolinium aluminum garnet Gd3Al5O12 , a related compound to the extensively studied Gd3Ga5O12 . We report on its magnetic properties at very low temperatures. We show that despite a freezing at about 300 mK, no magnetic transition is observed, suggesting the presence of a spin-liquid state down to the lowest temperatures, similarly to Gd3Ga5O12 , in spite of a larger ratio between exchange and dipolar interactions. Finally, the phase diagram as a function of field and temperature is strongly reminiscent of the one reported in Gd3Ga5O12 . This study reveals the robust nature of the spin-liquid phase for Gd ions on the garnet lattice, in stark contrast to Gd ions on the pyrochlore lattice for which a slight perturbation drives the compound into a range of magnetically ordered states.

Contrast-enhanced computed tomography plus gadolinium-ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging for gross classification of hepatocellular carcinoma.

PubMed

Chen, Chuang; Zhao, Hui; Fu, Xu; Huang, LuoShun; Tang, Min; Yan, XiaoPeng; Sun, ShiQuan; Jia, WenJun; Mao, Liang; Shi, Jiong; Chen, Jun; He, Jian; Zhu, Jin; Qiu, YuDong

2017-05-02

Accurate gross classification through imaging is critical for determination of hepatocellular carcinoma (HCC) patient prognoses and treatment strategies. The present retrospective study evaluated the utility of contrast-enhanced computed tomography (CE-CT) combined with gadolinium-ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) for diagnosis and classification of HCCs prior to surgery. Ninety-four surgically resected HCC nodules were classified as simple nodular (SN), SN with extranodular growth (SN-EG), confluent multinodular (CMN), or infiltrative (IF) types. SN-EG, CMN and IF samples were grouped as non-SN. The abilities of the two imaging modalities to differentiate non-SN from SN HCCs were assessed using the EOB-MRI hepatobiliary phase and CE-CT arterial, portal, and equilibrium phases. Areas under the ROC curves for non-SN diagnoses were 0.765 (95% confidence interval [CI]: 0.666-0.846) for CE-CT, 0.877 (95% CI: 0.793-0.936) for EOB-MRI, and 0.908 (95% CI: 0.830-0.958) for CE-CT plus EOB-MRI. Sensitivities, specificities, and accuracies with respect to identification of non-SN tumors of all sizes were 71.4%, 81.6%, and 75.5% for CE-CT; 96.4%, 78.9%, and 89.3% for EOB-MRI; and 98.2%, 84.2%, and 92.5% for CE-CT plus EOB-MRI. These results show that CE-CT combined with EOB-MRI offers a more accurate imaging evaluation for HCC gross classification than either modality alone.

Brain activation for response inhibition under gaming cue distraction in internet gaming disorder.

PubMed

Liu, Gin-Chung; Yen, Ju-Yu; Chen, Chiao-Yun; Yen, Cheng-Fang; Chen, Cheng-Sheng; Lin, Wei-Chen; Ko, Chih-Hung

2014-01-01

We evaluated neural substrates related to the loss of control in college students with internet gaming disorder (IGD). We hypothesized that deficit in response inhibition under gaming cue distraction was the possible mechanism for the loss of control internet use. Eleven cases of IGD and 11 controls performed Go/NoGo tasks with/without gaming distraction in the functional magnetic resonance imaging scanner. When the gaming picture was shown as background while individuals were performing Go/NoGo tasks, the IGD group committed more commission errors. The control group increased their brain activations more over the right dorsolateral prefrontal cortex (DLPFC) and superior parietal lobe under gaming cue distraction in comparison with the IGD group. Furthermore, brain activation of the right DLPFC and superior parietal lobe were negatively associated with performance of response inhibition among the IGD group. The results suggest that the function of response inhibition was impaired under gaming distraction among the IGD group, and individuals with IGD could not activate right DLPFC and superior parietal lobe to keep cognitive control and attention allocation for response inhibition under gaming cue distraction. This mechanism should be addressed in any intervention for IGD. Copyright © 2013. Published by Elsevier B.V.

Input and fate of anthropogenic estrogens and gadolinium in surface water and sewage plants in the hydrological basin of Prague (Czech Republic).

PubMed

Morteani, Giulio; Möller, Peter; Fuganti, Andrea; Paces, Tomas

2006-06-01

The concentration of the estrogens 17beta-estradiol, estriol, estrone, 17alpha-ethinylestradiol, mestranol and norethisterone and of the anthropogenic gadolinium (Gd(ant)) has been determined in the creeks and rivers, sewage treatment plants and water works of the city of Prague. The rapid degradation of estrogens in surface water allows the estrogen concentration gradient to be used as a very precise and sensitive guideline by which to pin-point sewage leaks into surface run-off water. The rather conservative behavior of Gd(ant) in surface and ground water documents in the present case the presence of sewage water in the surface water cycle.

Effect of gadolinium dopant on structural, magneto-transport, magnetic and thermo-power of Pr0.8Sr0.2MnO3

NASA Astrophysics Data System (ADS)

Poojary, Thrapthi; Babu, P. D.; Sanil, Tejaswini; Daivajna, Mamatha D.

2018-07-01

In the present investigation structural, magneto-transport, magnetic and thermo-power measurements of Gadolinium (Gd) doped Pr0.8-xGdxSr0.2MnO3 (0, 0.2, 0.25 and 0.3) manganites have been done. All the samples are single phased with orthorhombic structure. Temperature variation of resistance exhibits a high temperature transition occurring at 156 K and a low temperature cusp at around 95 K for pristine sample. With Gd doping resistance behavior shows insulating behavior throughout the whole temperature range. Magneto-Resistance (MR%) increases with Gd doping. A huge increase in thermo-electric power is observed with Gd doping.

Thiaflavan scavenges radicals and inhibits DNA oxidation: a story from the ferrocene modification.

PubMed

Lai, Hai-Wang; Liu, Zai-Qun

2014-06-23

4-Thiaflavan is a sulfur-substituted flavonoid with a benzoxathiin scaffold. The aim of this work is to compare abilities of sulfur and oxygen atom, hydroxyl groups, and ferrocene moiety at different positions of 4-thiaflavan to trap radicals and to inhibit DNA oxidation. It is found that abilities of thiaflavans to trap radicals and to inhibit DNA oxidation are increased in the presence of ferrocene moiety and are further improved by the electron-donating group attaching to thiaflavan skeleton. It can be concluded that the ferrocene moiety plays the major role for thiaflavans to be antioxidants even in the absence of phenolic hydroxyl groups. On the other hand, the antioxidant effectiveness of phenolic hydroxyl groups in thiaflavans can be improved by the electron-donating group. The influences of sulfur and oxygen atoms in thiaflavans on the antioxidant property of para-hydroxyl group exhibit different manners when the thiaflavans are used to trap radicals and to inhibit DNA oxidation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Ultrasound guidance to perform intra-articular injection of gadolinium-based contrast material for magnetic resonance arthrography as an alternative to fluoroscopy: the time is now.

PubMed

Messina, Carmelo; Banfi, Giuseppe; Aliprandi, Alberto; Mauri, Giovanni; Secchi, Francesco; Sardanelli, Francesco; Sconfienza, Luca Maria

2016-05-01

Magnetic resonance (MR) imaging has been definitively established as the reference standard in the evaluation of joints in the body. Similarly, magnetic resonance arthrography has emerged as a technique that has been proven to increase significantly the diagnostic performance if compared with conventional MR imaging, especially when dealing with fibrocartilage and articular cartilage abnormalities. Diluted gadolinium can be injected in the joint space using different approaches: under palpation using anatomic landmarks or using an imaging guidance, such as fluoroscopy, computed tomography, or ultrasound. Fluoroscopy has been traditionally used, but the involvement of ionizing radiation should represent a remarkable limitation of this modality. Conversely, ultrasound has emerged as a feasible, cheap, quick, and radiation-free modality that can be used to inject joints, with comparable accuracy of fluoroscopy. In the present paper, we discuss the advantages and disadvantages of using fluoroscopy or ultrasound in injecting gadolinium-based contrast agents in joints to perform magnetic resonance arthrography, also in view of the new EuroSAFE Imaging initiative promoted by the European Society of Radiology and the recent updates to the European Atomic Energy Community 2013/59 directive on the medical use of ionizing radiation. • Intra-articular contrast agent injection can be performed using different imaging modalities • Fluoroscopy is widely used, but uses ionizing radiation • Ultrasound is an accurate, quick, and radiation-free modality for joint injection • X-rays should be avoided when other radiation-free modalities can be used.

Gadolinium compounds signaling through TLR4 and TLR7 in normal human macrophages: establishment of a proinflammatory phenotype and implications for the pathogenesis of nephrogenic systemic fibrosis.

PubMed

Wermuth, Peter J; Jimenez, Sergio A

2012-07-01

Nephrogenic systemic sibrosis is a progressive disorder occurring in some renal insufficiency patients exposed to gadolinium-based contrast agents (GdBCA). Previous studies demonstrated that the GdBCA Omniscan upregulated several innate immunity pathways in normal differentiated human macrophages, induced rapid nuclear localization of the transcription factor NF-κB, and increased the expression and production of numerous profibrotic/proinflammatory cytokines, chemokines, and growth factors. To further examine GdBCA stimulation of the innate immune system, cultured human embryonic kidney 293 cells expressing one of seven different human TLRs or one of two human nucleotide-binding oligomerization domain-like receptors were exposed in vitro for 24 h to various GdBCA. The signaling activity of each compound was evaluated by its ability to activate an NF-κB-inducible reporter gene. Omniscan and gadodiamide induced strong TLR4- and TLR7-mediated reporter gene activation. The other Gd compounds examined failed to induce reporter gene activation. TLR pathway inhibition using chloroquine or an inhibitor of IL-1R-associated kinases 1 and 4 in normal differentiated human macrophages abrogated Omniscan-induced gene expression. Omniscan and gadodiamide signaling via TLRs 4 and 7 resulted in increased production and expression of numerous proinflammatory/profibrotic cytokines, chemokines, and growth factors, including CXCL10, CCL2, CCL8, CXCL12, IL-4, IL-6, TGF-β, and vascular endothelial growth factor. These observations suggest that TLR activation by environmental stimuli may participate in the pathogenesis of nephrogenic systemic fibrosis and of other fibrotic disorders including systemic sclerosis.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) of cadaveric shoulders: comparison of contrast dynamics in hyaline and fibrous cartilage after intraarticular gadolinium injection.

PubMed

Wiener, E; Hodler, J; Pfirrmann, C W A

2009-01-01

Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) is a novel method to investigate cartilaginous and fibrocartilaginous structures. To investigate the contrast dynamics in hyaline and fibrous cartilage of the glenohumeral joint after intraarticular injection of gadopentetate dimeglumine. Transverse T(1) maps were acquired on a 1.5T scanner before and after intraarticular injection of 2.0 mmol/l gadopentetate dimeglumine in five cadaveric shoulders using a dual flip angle three-dimensional gradient echo (3D-GRE) sequence. The acquisition time for the T(1) maps was 5 min 5 s for the whole shoulder. Measurements were repeated every 15 min over 2.5 hours. Regions of interest (ROIs) covering the glenoid cartilage and the labrum were drawn to assess the temporal evolution of the relaxation parameters. T(1) of unenhanced hyaline cartilage of the glenoid was 568+/-34 ms. T(1) of unenhanced fibrous cartilage of the labrum was 552+/-38 ms. Significant differences (P=0.002 and 0.03) in the relaxation parameters were already measurable after 15 min. After 2 to 2.5 hours, hyaline and fibrous cartilage still demonstrated decreasing relaxation parameters, with a larger range of the T(1)(Gd) values in fibrous cartilage. T(1) and triangle Delta R(1) values of hyaline and fibrous cartilage after 2.5 hours were 351+/-16 ms and 1.1+/-0.09 s(-1), and 332+/-31 ms and 1.2+/-0.1 s(-1), respectively. A significant decrease in T(1)(Gd) was found 15 min after intraarticular contrast injection. Contrast accumulation was faster in hyaline than in fibrous cartilage. After 2.5 hours, contrast accumulation showed a higher rate of decrease in hyaline cartilage, but neither hyaline nor fibrous cartilage had reached equilibrium.

Emotional Response Inhibition in Bipolar Disorder: A Functional Magnetic Resonance Imaging Study of Trait- and State-Related Abnormalities

PubMed Central

Hummer, Tom A.; Hulvershorn, Leslie A.; Karne, Harish S.; Gunn, Abigail D.; Wang, Yang; Anand, Amit

2018-01-01

Background Impaired response inhibition and poor impulse control are hallmarks of the manic phase of bipolar disorder but are also present during depressive and, to a lesser degree, euthymic periods. The neural mechanisms underlying these impairments are poorly understood, including how mechanisms are related to bipolar trait or state effects. Methods One-hundred four unmedicated participants with bipolar mania (BM) (n = 30), bipolar depression (BD) (n = 30), bipolar euthymia (BE) (n = 14), and healthy control subjects (n = 30) underwent functional magnetic resonance imaging during emotional and nonemotional go/no-go tasks. The go/no-go task requires participants to press a button for go stimuli, while inhibiting the response to no-go trials. In separate blocks, participants inhibited the response to happy faces, sad faces, or letters. Results The BE group had higher insula activity during happy face inhibition and greater activity in left inferior frontal gyrus during sad face inhibition, demonstrating bipolar trait effects. Relative to the BE group, BD and BM groups demonstrated lower insula activity during inhibition of happy faces, though the depressed sample had lower activity than manic patients. The BD and BM groups had a greater response to inhibiting sad faces in emotion processing and regulation regions, including putamen, insula, and lateral prefrontal cortex. The manic group also had higher activity in insula and putamen during neutral letter inhibition. Conclusions These results suggest distinct trait- and state-related neural abnormalities during response inhibition in bipolar disorder, with implications for future research and treatment. PMID:22871393

Cinnamic acid amides from Tribulus terrestris displaying uncompetitive α-glucosidase inhibition.

PubMed

Song, Yeong Hun; Kim, Dae Wook; Curtis-Long, Marcus J; Park, Chanin; Son, Minky; Kim, Jeong Yoon; Yuk, Heung Joo; Lee, Keun Woo; Park, Ki Hun

2016-05-23

The α-glucosidase inhibitory potential of Tribulus terrestris extracts has been reported but as yet the active ingredients are unknown. This study attempted to isolate the responsible metabolites and elucidate their inhibition mechanism of α-glucosidase. By fractionating T. terristris extracts, three cinnamic acid amide derivatives (1-3) were ascertained to be active components against α-glucosidase. The lead structure, N-trans-coumaroyltyramine 1, showed significant inhibition of α-glucosidase (IC50 = 0.42 μM). Moreover, all active compounds displayed uncompetitive inhibition mechanisms that have rarely been reported for α-glucosidase inhibitors. This kinetic behavior was fully demonstrated by showing a decrease of both Km and Vmax, and Kik/Kiv ratio ranging between 1.029 and 1.053. We progressed to study how chemical modifications to the lead structure 1 may impact inhibition. An α, β-unsaturation carbonyl group and hydroxyl group in A-ring of cinnamic acid amide emerged to be critical functionalities for α-glucosidase inhibition. The molecular modeling study revealed that the inhibitory activities are tightly related to π-π interaction as well as hydrogen bond interaction between enzyme and inhibitors. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Normal spinal bone marrow in adults: dynamic gadolinium-enhanced MR imaging.

PubMed

Montazel, Jean-Luc; Divine, Marine; Lepage, Eric; Kobeiter, Hicham; Breil, Stephane; Rahmouni, Alain

2003-12-01

To determine the patterns of dynamic enhancement of normal spinal bone marrow in adults at gadolinium-enhanced magnetic resonance (MR) imaging and the changes that occur with aging. Dynamic contrast material-enhanced MR imaging of the thoracolumbar spine was performed in 71 patients. The maximum percentage of enhancement (Emax), enhancement slope, and enhancement washout were determined from bone marrow enhancement time curves (ETCs). The bone marrow signal intensity on T1-weighted spin-echo MR images was qualitatively classified into three grade categories. Quantitative ETC values were correlated with patient age and bone marrow fat content grade. Statistical analysis included mean t test comparison, analysis of variance, and regression analysis of the correlations between age and quantitative MR parameters. Emax, slope, and washout varied widely among the patients. Emax values were obtained within 1 minute after contrast material injection and ranged from 0% to 430%. Emax values were significantly higher in patients younger than 40 years than in those aged 40 years or older (P <.001). These values decreased with increasing age in a logarithmic relationship (r = 0.71). Emax values decreased as fat content increased, but some overlap among the fat content grades was noted. Analysis of variance revealed that Emax was significantly related to age (younger than 40 years vs 40 years or older) (P <.001) and fat content grade (P <.001) but not significantly related to sex. Dynamic contrast-enhanced MR imaging patterns of normal spinal bone marrow are dependent mainly on patient age and fat content.

NLRP3 inflammasome inhibition is disrupted in a group of auto-inflammatory disease CAPS mutations.

PubMed

Mortimer, Leanne; Moreau, France; MacDonald, Justin A; Chadee, Kris

2016-10-01

Inflammasomes are positioned to rapidly escalate the intensity of inflammation by activating interleukin (IL)-1β, IL-18 and cell death by pyroptosis. However, negative regulation of inflammasomes remains poorly understood, as is the signaling cascade that dampens inflammasome activity. We found that rapid NLRP3 inflammasome activation was directly inhibited by protein kinase A (PKA), which was induced by prostaglandin E2 (PGE2) signaling via the PGE2 receptor E-prostanoid 4 (EP4). PKA directly phosphorylated the cytoplasmic receptor NLRP3 and attenuated its ATPase function. We found that Ser295 in human NLRP3 was critical for rapid inhibition and PKA phosphorylation. Mutations in NLRP3-encoding residues adjacent to Ser295 have been linked to the inflammatory disease CAPS (cryopyrin-associated periodic syndromes). NLRP3-S295A phenocopied the human CAPS mutants. These data suggest that negative regulation at Ser295 is critical for restraining the NLRP3 inflammasome and identify a molecular basis for CAPS-associated NLRP3 mutations.

Inhibition of metallopeptidases by flavonoids and related compounds.

PubMed

Bormann, H; Melzig, M F

2000-02-01

To elucidate possible mechanisms of activity in medicinal plants containing flavonoids, the inhibitory potency of twenty flavones, flavonols, flavanones, phenylacrylic acids and various hydroxylated phenylacetic acids on the activity of neutral endopeptidase (NEP; EC 3.4.24.11), angiotensin-converting enzyme (ACE; EC 3.4.15.1) and aminopeptidase N (APN; EC 3.4.11.2) was investigated in vitro. The screening generally resulted that inhibition of these enzymes requires free hydroxyl groups at the flavone molecule. Flavone and methoxylated compounds (sinensetin) were without effects. Flavonoids with free hydroxyl functions in position 3',4' and 5,7 inhibited the activity of NEP (quercetin, luteolin, fisetin), with myricetin (IC50 = 42 microM) as strongest inhibitor. Inhibition of ACE and APN did not depend on this class of compounds and substitution pattern. E.g. 3,4-dihydroxyphenylacetic acid and 4-methylcatechol (urinary metabolites of flavonoids) also inhibited both APN and ACE activity, but not NEP activity. The results demonstrate that some of the pharmacological activities of flavonoids might be related to the inhibition of metallopeptidases responsible for the splitting of regulatory neuropeptides.

Recent progress in advanced optical materials based on gadolinium aluminate garnet (Gd3Al5O12)

PubMed Central

Li, Ji-Guang; Sakka, Yoshio

2015-01-01

This review article summarizes the recent achievements in stabilization of the metastable lattice of gadolinium aluminate garnet (Gd3Al5O12, GAG) and the related developments of advanced optical materials, including down-conversion phosphors, up-conversion phosphors, transparent ceramics, and single crystals. Whenever possible, the materials are compared with their better known YAG and LuAG counterparts to demonstrate the merits of the GAG host. It is shown that novel emission features and significantly improved luminescence can be attained for a number of phosphor systems with the more covalent GAG lattice and the efficient energy transfer from Gd3+ to the activator. Ce3+ doped GAG-based single crystals and transparent ceramics are also shown to simultaneously possess the advantages of high theoretical density, fast scintillation decay, and high light yields, and hold great potential as scintillators for a wide range of applications. The unresolved issues are also pointed out. PMID:27877750

Recent progress in advanced optical materials based on gadolinium aluminate garnet (Gd3Al5O12)

NASA Astrophysics Data System (ADS)

Li, Ji-Guang; Sakka, Yoshio

2015-02-01

This review article summarizes the recent achievements in stabilization of the metastable lattice of gadolinium aluminate garnet (Gd3Al5O12, GAG) and the related developments of advanced optical materials, including down-conversion phosphors, up-conversion phosphors, transparent ceramics, and single crystals. Whenever possible, the materials are compared with their better known YAG and LuAG counterparts to demonstrate the merits of the GAG host. It is shown that novel emission features and significantly improved luminescence can be attained for a number of phosphor systems with the more covalent GAG lattice and the efficient energy transfer from Gd3+ to the activator. Ce3+ doped GAG-based single crystals and transparent ceramics are also shown to simultaneously possess the advantages of high theoretical density, fast scintillation decay, and high light yields, and hold great potential as scintillators for a wide range of applications. The unresolved issues are also pointed out.

Myocardial infarct sizing by late gadolinium-enhanced MRI: Comparison of manual, full-width at half-maximum, and n-standard deviation methods.

PubMed

Zhang, Lin; Huttin, Olivier; Marie, Pierre-Yves; Felblinger, Jacques; Beaumont, Marine; Chillou, Christian DE; Girerd, Nicolas; Mandry, Damien

2016-11-01

To compare three widely used methods for myocardial infarct (MI) sizing on late gadolinium-enhanced (LGE) magnetic resonance (MR) images: manual delineation and two semiautomated techniques (full-width at half-maximum [FWHM] and n-standard deviation [SD]). 3T phase-sensitive inversion-recovery (PSIR) LGE images of 114 patients after an acute MI (2-4 days and 6 months) were analyzed by two independent observers to determine both total and core infarct sizes (TIS/CIS). Manual delineation served as the reference for determination of optimal thresholds for semiautomated methods after thresholding at multiple values. Reproducibility and accuracy were expressed as overall bias ± 95% limits of agreement. Mean infarct sizes by manual methods were 39.0%/24.4% for the acute MI group (TIS/CIS) and 29.7%/17.3% for the chronic MI group. The optimal thresholds (ie, providing the closest mean value to the manual method) were FWHM30% and 3SD for the TIS measurement and FWHM45% and 6SD for the CIS measurement (paired t-test; all P > 0.05). The best reproducibility was obtained using FWHM. For TIS measurement in the acute MI group, intra-/interobserver agreements, from Bland-Altman analysis, with FWHM30%, 3SD, and manual were -0.02 ± 7.74%/-0.74 ± 5.52%, 0.31 ± 9.78%/2.96 ± 16.62% and -2.12 ± 8.86%/0.18 ± 16.12, respectively; in the chronic MI group, the corresponding values were 0.23 ± 3.5%/-2.28 ± 15.06, -0.29 ± 10.46%/3.12 ± 13.06% and 1.68 ± 6.52%/-2.88 ± 9.62%, respectively. A similar trend for reproducibility was obtained for CIS measurement. However, semiautomated methods produced inconsistent results (variabilities of 24-46%) compared to manual delineation. The FWHM technique was the most reproducible method for infarct sizing both in acute and chronic MI. However, both FWHM and n-SD methods showed limited accuracy compared to manual delineation. J. Magn. Reson. Imaging 2016;44:1206-1217. © 2016 International Society for Magnetic Resonance in Medicine.

Influence of impulsiveness on emotional modulation of response inhibition: An ERP study.

PubMed

Messerotti Benvenuti, Simone; Sarlo, Michela; Buodo, Giulia; Mento, Giovanni; Palomba, Daniela

2015-10-01

To examine how impulsiveness influences the emotional modulation of behavioral and neural correlates of response inhibition. Twenty-nine healthy individuals scoring high (HI, N=16) or low (LI, N=13) on motor impulsiveness performed an emotional Go/Nogo task, including the presentation of pleasant, neutral and unpleasant pictures. Behavioral [reaction times (RTs), accuracy to Go and Nogo trials] and neural (Nogo-N2 and Nogo-P3) correlates of response inhibition were compared between HI and LI groups. Larger Nogo-P3 was found for emotional than neutral stimuli in HI relative to LI group. Faster RTs to Go stimuli and lower accuracy to Nogo stimuli were correlated with larger Nogo-P3 in HI, but not LI, group. No significant interactions between emotion content and impulsiveness for Nogo-N2 and behavioral measures were noted. Impulsiveness influences the emotional modulation of response inhibition by potentiating the response tendencies evoked by the emotional stimuli. Accordingly, high impulsive individuals may need an increased and/or more effortful response inhibition in order to counteract the prepotent tendency to respond elicited by the combination of high trait impulsiveness and high emotional arousal. The present study suggests the importance to examine how pathological impulsiveness may interact with emotional arousal in modulating response inhibition. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Silica nanoparticle-based dual imaging colloidal hybrids: cancer cell imaging and biodistribution

PubMed Central

Lee, Haisung; Sung, Dongkyung; Kim, Jinhoon; Kim, Byung-Tae; Wang, Tuntun; An, Seong Soo A; Seo, Soo-Won; Yi, Dong Kee

2015-01-01

In this study, fluorescent dye-conjugated magnetic resonance (MR) imaging agents were investigated in T mode. Gadolinium-conjugated silica nanoparticles were successfully synthesized for both MR imaging and fluorescence diagnostics. Polyamine and polycarboxyl functional groups were modified chemically on the surface of the silica nanoparticles for efficient conjugation of gadolinium ions. The derived gadolinium-conjugated silica nanoparticles were investigated by zeta potential analysis, transmission electron microscopy, inductively coupled plasma mass spectrometry, and energy dispersive x-ray spectroscopy. MR equipment was used to investigate their use as contrast-enhancing agents in T1 mode under a 9.4 T magnetic field. In addition, we tracked the distribution of the gadolinium-conjugated nanoparticles in both lung cancer cells and organs in mice. PMID:26357472

A New Group of Phage Anti-CRISPR Genes Inhibits the Type I-E CRISPR-Cas System of Pseudomonas aeruginosa

PubMed Central

Pawluk, April; Bondy-Denomy, Joseph; Cheung, Vivian H. W.; Maxwell, Karen L.; Davidson, Alan R.

2014-01-01

ABSTRACT CRISPR-Cas systems are one of the most widespread phage resistance mechanisms in prokaryotes. Our lab recently identified the first examples of phage-borne anti-CRISPR genes that encode protein inhibitors of the type I-F CRISPR-Cas system of Pseudomonas aeruginosa. A key question arising from this work was whether there are other types of anti-CRISPR genes. In the current work, we address this question by demonstrating that some of the same phages carrying type I-F anti-CRISPR genes also possess genes that mediate inhibition of the type I-E CRISPR-Cas system of P. aeruginosa. We have discovered four distinct families of these type I-E anti-CRISPR genes. These genes do not inhibit the type I-F CRISPR-Cas system of P. aeruginosa or the type I-E system of Escherichia coli. Type I-E and I-F anti-CRISPR genes are located at the same position in the genomes of a large group of related P. aeruginosa phages, yet they are found in a variety of combinations and arrangements. We have also identified functional anti-CRISPR genes within nonprophage Pseudomonas genomic regions that are likely mobile genetic elements. This work emphasizes the potential importance of anti-CRISPR genes in phage evolution and lateral gene transfer and supports the hypothesis that more undiscovered families of anti-CRISPR genes exist. Finally, we provide the first demonstration that the type I-E CRISPR-Cas system of P. aeruginosa is naturally active without genetic manipulation, which contrasts with E. coli and other previously characterized I-E systems. PMID:24736222

Impaired right inferior frontal gyrus response to contextual cues in male veterans with PTSD during response inhibition.

PubMed

van Rooij, Sanne J H; Rademaker, Arthur R; Kennis, Mitzy; Vink, Matthijs; Kahn, René S; Geuze, Elbert

2014-09-01

Posttraumatic stress disorder (PTSD) is often associated with impaired fear inhibition and decreased safety cue processing; however, studies capturing the cognitive aspect of inhibition and contextual cue processing are limited. In this fMRI study, the role of contextual cues in response inhibition was investigated. Male medication-naive war veterans with PTSD, male control veterans (combat controls) and healthy nonmilitary men (healthy controls) underwent fMRI while performing the stop-signal anticipation task (SSAT). The SSAT evokes 2 forms of response inhibition: reactive inhibition (outright stopping) and proactive inhibition (anticipation of stopping based on contextual cues). We enrolled 28 veterans with PTSD, 26 combat controls and 25 healthy controls in our study. Reduced reactive inhibition was observed in all veterans, both with and without PTSD, but not in nonmilitary controls, whereas decreased inhibition of the left pre/postcentral gyrus appeared to be specifically associated with PTSD. Impaired behavioural proactive inhibition was also specific to PTSD. Furthermore, the PTSD group showed a reduced right inferior frontal gyrus response during proactive inhibition compared with the combat control group. Most patients with PTSD had comorbid psychiatric disorders, but such comorbidity is common in patients with PTSD. Also, the education level (estimate of intelligence) of participants, but not of their parents, differed among the groups. Our findings of reduced proactive inhibition imply that patients with PTSD show reduced contextual cue processing. These results complement previous findings on fear inhibition and demonstrate that contextual cue processing in patients with PTSD is also reduced during cognitive processes, indicating a more general deficit.

Impaired right inferior frontal gyrus response to contextual cues in male veterans with PTSD during response inhibition

PubMed Central

van Rooij, Sanne J.H.; Rademaker, Arthur R.; Kennis, Mitzy; Vink, Matthijs; Kahn, René S.; Geuze, Elbert

2014-01-01

Background Posttraumatic stress disorder (PTSD) is often associated with impaired fear inhibition and decreased safety cue processing; however, studies capturing the cognitive aspect of inhibition and contextual cue processing are limited. In this fMRI study, the role of contextual cues in response inhibition was investigated. Methods Male medication-naive war veterans with PTSD, male control veterans (combat controls) and healthy nonmilitary men (healthy controls) underwent fMRI while performing the stop-signal anticipation task (SSAT). The SSAT evokes 2 forms of response inhibition: reactive inhibition (outright stopping) and proactive inhibition (anticipation of stopping based on contextual cues). Results We enrolled 28 veterans with PTSD, 26 combat controls and 25 healthy controls in our study. Reduced reactive inhibition was observed in all veterans, both with and without PTSD, but not in nonmilitary controls, whereas decreased inhibition of the left pre/postcentral gyrus appeared to be specifically associated with PTSD. Impaired behavioural proactive inhibition was also specific to PTSD. Furthermore, the PTSD group showed a reduced right inferior frontal gyrus response during proactive inhibition compared with the combat control group. Limitations Most patients with PTSD had comorbid psychiatric disorders, but such comorbidity is common in patients with PTSD. Also, the education level (estimate of intelligence) of participants, but not of their parents, differed among the groups. Conclusion Our findings of reduced proactive inhibition imply that patients with PTSD show reduced contextual cue processing. These results complement previous findings on fear inhibition and demonstrate that contextual cue processing in patients with PTSD is also reduced during cognitive processes, indicating a more general deficit. PMID:24886789

Effect of intravenous gadolinium-DTPA on diffusion-weighted imaging of brain tumors: a short temporal interval assessment.

PubMed

Li, Xiang; Qu, Jin-Rong; Luo, Jun-Peng; Li, Jing; Zhang, Hong-Kai; Shao, Nan-Nan; Kwok, Keith; Zhang, Shou-Ning; Li, Yan-le; Liu, Cui-Cui; Zee, Chi-Shing; Li, Hai-Liang

2014-09-01

To determine the effect of intravenous administration of gadolinium (Gd) contrast medium (Gd-DTPA) on diffusion-weighted imaging (DWI) for the evaluation of normal brain parenchyma vs. brain tumor following a short temporal interval. Forty-four DWI studies using b values of 0 and 1000 s/mm(2) were performed before, immediately after, 1 min after, 3 min after, and 5 min after the administration of Gd-DTPA on 62 separate lesions including 15 meningioma, 17 glioma and 30 metastatic lesions. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and apparent diffusion coefficient (ADC) values of the brain tumor lesions and normal brain tissues were measured on pre- and postcontrast images. Statistical analysis using paired t-test between precontrast and postcontrast data were obtained on three brain tumors and normal brain tissue. The SNR and CNR of brain tumors and the SNR of normal brain tissue showed no statistical differences between pre- and postcontrast (P > 0.05). The ADC values on the three cases of brain tumors demonstrated significant initial increase on the immediate time point (P < 0.01) and decrease on following the 1 min time point (P < 0.01) after contrast. Significant decrease of ADC value was still found at 3min and 5min time point in the meningioma group (P < 0.01) with gradual normalization over time. The ADC values of normal brain tissues demonstrated significant initial elevation on the immediately postcontrast DWI sequence (P < 0.01). Contrast medium can cause a slight but statistically significant change on the ADC value within a short temporal interval after the contrast administration. The effect is both time and lesion-type dependent. © 2013 Wiley Periodicals, Inc.

Mirror-touch synaesthesia: Difficulties inhibiting the other.

PubMed

Santiesteban, Idalmis; Bird, Geoffrey; Tew, Oliver; Cioffi, Maria Cristina; Banissy, Michael J

2015-10-01

Individuals with mirror touch synaesthesia (MTS) experience touch on their own body when observing others being touched. A recent account proposes that such rare experiences could be linked to impairment in self-other representations. Here we tested participants with MTS on a battery of social cognition tests and found that compared to non-synaesthete controls, the MTS group showed impairment in imitation-inhibition but not in visual perspective taking or theory of mind. Although all of these socio-cognitive abilities rely on the control of self-other representations, they differ as to whether the self, or the other, should be preferentially represented. For imitation-inhibition, representations of the other should be inhibited and self-representations should be enhanced, whereas the opposite is true for visual perspective taking and theory of mind. These findings suggest that MTS is associated with a specific deficit in inhibiting representation of other individuals and shed light on the fractionability of processes underlying typical social cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Caustic Precipitation of Plutonium and Uranium with Gadolinium as a Neutron Poison

DOE Office of Scientific and Technical Information (OSTI.GOV)

ANN, VISSER

2005-04-14

The caustic precipitation of plutonium (Pu) and uranium (U) from Pu and U containing waste solutions has been investigated to determine whether gadolinium (Gd) could be used as a neutron poison for precipitation with greater than a fissile mass containing both Pu and enriched U. Precipitation experiments were performed using both actual samples and simulant solutions with a range of 2.6-5.16 g/L U and 0-4.3 to 1 U to Pu. Analyses were performed on solutions at intermediate pH to determine the partitioning of elements for accident scenarios. When both Pu and U were present in the solution, precipitation began atmore » pH 4.5 and by pH 7, 99 percent of Pu and U had precipitated. When complete neutralization was achieved at pH greater than 14 with 1.2 M excess OH-, greater than 99 percent of Pu, U, and Gd had precipitated. At pH greater than 14, the particles sizes were larger and the distribution was a single mode. The ratio of hydrogen to fissile atoms in the precipitate was determined after both settling and centrifuging and indicates that sufficient water was associated with the precipitates to provide the needed neutron moderation for Gd to prevent a criticality in solutions containing up to 4.3 to 1 U to Pu and up to 5.16 g/L U.« less

Local and global inhibition in bilingual word production: fMRI evidence from Chinese-English bilinguals

PubMed Central

Guo, Taomei; Liu, Hongyan; Misra, Maya; Kroll, Judith F.

2011-01-01

The current study examined the neural correlates associated with local and global inhibitory processes used by bilinguals to resolve interference between competing responses. Two groups of participants completed both blocked and mixed picture naming tasks while undergoing functional magnetic resonance imaging (fMRI). One group first named a set of pictures in L1, and then named the same pictures in L2. The other group first named pictures in L2, and then in L1. After the blocked naming tasks, both groups performed a mixed language naming task (i.e., naming pictures in either language according to a cue). The comparison between the blocked and mixed naming tasks, collapsed across groups, was defined as the local switching effect, while the comparison between blocked naming in each language was defined as the global switching effect. Distinct patterns of neural activation were found for local inhibition as compared to global inhibition in bilingual word production. Specifically, the results suggest that the dorsal anterior cingulate cortex (ACC) and the supplementary motor area (SMA) play important roles in local inhibition, while the dorsal left frontal gyrus and parietal cortex are important for global inhibition. PMID:21440072

The kampo medicine Daikenchuto inhibits peritoneal fibrosis in mice.

PubMed

Kitamura, Mineaki; Nishino, Tomoya; Obata, Yoko; Oka, Satoru; Abe, Shinichi; Muta, Kumiko; Ozono, Yoshiyuki; Koji, Takehiko; Kohno, Shigeru

2015-01-01

Long-term peritoneal dialysis therapy causes inflammation and histological changes in the peritoneal membrane. Inflammation generally activates fibroblasts and results in fibroblast-myofibroblast differentiation. Heat-shock protein 47 (HSP 47), a collagen-specific molecular chaperone, is localized in myofibroblasts and is involved in the progression of peritoneal fibrosis. Daikenchuto (DKT), a Kampo medicine, is used to prevent postoperative colon adhesion. It inhibits inflammation and HSP 47 expression in the gastrointestinal tract. We examined the effect of DKT on chlorhexidine gluconate (CG)-induced peritoneal fibrosis in mice injected with 0.1% CG dissolved in 15% ethanol. DKT was dissolved in the drinking water. Histological changes were assessed using Masson trichrome staining. Cells expressing α-smooth muscle actin (α-SMA), HSP 47, phospho-Smad 2/3, F4/80, and monocyte chemotactic protein-1 were examined immunohistochemically. Compared with the control group, the peritoneal tissues of the CG group were markedly thickened, and the number of cells expressing α-SMA, HSP 47, phospho-Smad 2/3, F4/80, and monocyte chemotactic protein-1 was significantly increased. However, these changes were inhibited in the DKT-treated group. These results indicate that DKT can prevent peritoneal fibrosis by inhibiting inflammation and HSP 47 expression.

Factors Inhibiting Hispanic Parents' School Involvement

ERIC Educational Resources Information Center

Smith, Jay; Stern, Kenneth; Shatrova, Zhanna

2008-01-01

Factors inhibiting Hispanic parental involvement in non-metropolitan area schools were studied. With the mandates of No Child Left Behind intensifying the need to improve the academic achievement of all at-risk groups of students in American schools, and with the relatively new phenomenon of large numbers of Hispanics settling in non-metropolitan…

Kinetics and Mechanism Study of Competitive Inhibition of Jack-Bean Urease by Baicalin

PubMed Central

Tan, Lirong; Su, Jiyan; Wu, Dianwei; Yu, Xiaodan; Su, Zuqing; Wu, Xiaoli; Kong, Songzhi; Lai, Xiaoping; Lin, Ji; Su, Ziren

2013-01-01

Baicalin (BA) is the principal component of Radix Scutellariae responsible for its pharmacological activity. In this study, kinetics and mechanism of inhibition by BA against jack-bean urease were investigated for its therapeutic potential. It was revealed that the IC50 of BA against jack-bean urease was 2.74 ± 0.51 mM, which was proved to be a competitive and concentration-dependent inhibition with slow-binding progress curves. The rapid formation of initial BA-urease complex with an inhibition constant of K i = 3.89 × 10−3 mM was followed by a slow isomerization into the final complex with an overall inhibition constant of K i* = 1.47 × 10−4 mM. High effectiveness of thiol protectors against BA inhibition indicated that the strategic role of the active-site sulfhydryl group of the urease was involved in the blocking process. Moreover, the inhibition of BA was proved to be reversible due to the fact that urease could be reactivated by dithiothreitol but not reactant dilution. Molecular docking assay suggested that BA made contacts with the important activating sulfhydryl group Cys-592 residues and restricted the mobility of the active-site flap. Taken together, it could be deduced that BA was a competitive inhibitor targeting thiol groups of urease in a slow-binding manner both reversibly and concentration-dependently, serving as a promising urease inhibitor for treatments on urease-related diseases. PMID:24198731

Anxiety Impacts Cognitive Inhibition in Remitted Anorexia Nervosa.

PubMed

Ely, Alice V; Wierenga, Christina E; Kaye, Walter H

2016-07-01

Eating disorders are complex psychiatric disorders, associated with alterations in neural and cognitive functioning. Research suggests inhibition and set-shifting deficits in anorexia nervosa (AN), but less is known about the persistence of these deficits after recovery, or their relationship to comorbid psychiatric symptoms. Women aged 19-45 remitted from AN (RAN, N = 47) and controls (CW, N = 24) completed the Delis-Kaplan Executive Function System Color-Word Interference Test. It was hypothesized that RAN, and those with higher anxiety or depression, would demonstrate worse Inhibition and Switching task performance than CW. Differences in performance between groups trended toward significance on Inhibition Ratio (p = 0.08) but were nonsignificant on Inhibition/Switching Ratio (p = 0.93). A model including State Anxiety and diagnosis revealed a significant independent effect of State Anxiety (p = 0.026), but not of diagnosis nor their interaction. Regressing State Anxiety on Color-Word Interference Test Inhibition among just the RAN group was significant [β = 0.37, t(46) = 2.63, p = 0.012] but among just CW was not (p = 0.54). Interference control for neutral stimuli is influenced by anxiety in women with a history of AN. Anxiety is linked with greater symptom severity among AN individuals, and state anxiety may account for larger deficits seen on tasks using disorder-specific stimuli. Future research is warranted to elucidate the nature of neuropsychological deficits in eating disorders. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Inhibition, Executive Function, and Freezing of Gait

PubMed Central

Cohen, Rajal G.; Klein, Krystal A.; Nomura, Mariko; Fleming, Michael; Mancini, Martina; Giladi, Nir; Nutt, John G.; Horak, Fay B.

2014-01-01

Background Studies suggest that freezing of gait (FoG) in people with Parkinson’s disease (PD) is associated with declines in executive function (EF). However, EF is multi-faceted, including three dissociable components: inhibiting prepotent responses, switching between task sets, and updating working memory. Objective This study investigated which aspect of EF is most strongly associated with FoG in PD. Method Three groups were studied: adults with PD (with and without FoG) and age-matched, healthy adults. All participants completed a battery of cognitive tasks previously shown to discriminate among the three EF components. Participants also completed a turning-in-place task that was scored for FoG by neurologists blind to subjects’ self-reported FoG. Results Compared to both other groups, participants with FoG showed significant performance deficits in tasks associated with inhibitory control, even after accounting for differences in disease severity, but no significant deficits in task-switching or updating working memory. Surprisingly, the strongest effect was an intermittent tendency of participants with FoG to hesitate, and thus miss the response window, on go trials in the Go-Nogo task. The FoG group also made slower responses in the conflict condition of the Stroop task. Physician-rated FoG scores were correlated both with failures to respond on go trials and with failures to inhibit responses on nogo trials in the Go-Nogo task. Conclusion These results suggest that FoG is associated with a specific inability to appropriately engage and release inhibition, rather than with a general executive deficit. PMID:24496099

The magnetic, relaxometric, and optical properties of gadolinium-catalyzed single walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Sitharaman, Balaji; Jacobson, Barry D.; Wadghiri, Youssef Z.; Bryant, Henry; Frank, Joseph

2013-04-01

We report the magnetic behavior, relaxometry, phantom magnetic resonance imaging (MRI), and near-infrared (NIR) photoluminescence spectroscopy of gadolinium (Gd) catalyzed single-walled carbon nanotubes (Gd-SWCNTs). Gd-SWCNTs are paramagnetic with an effective magnetic moment of 7.29 μB. Gd-SWCNT solutions show high r1 and r2 relaxivities at very low (0.01 MHz) to clinically relevant (61 MHz) magnetic fields (r1 ≥ 130 mM-1 s-1, r2 ≥ 160 mM-1 s-1). Analysis of nuclear magnetic resonance dispersion profiles using Solomon, Bloembergen, and Morgan equations suggests that multiple structural and dynamic parameters such as rotational correlation time τR, rate of water exchange τM, and the number of fast-exchanging water molecules within the inner sphere q may be responsible for the increase in r1 and r2 relaxivity. The T1 weighted MRI signal intensity (gradient echo sequence; repetition time (TR) = 66 ms, echo time (TE) = 3 ms, flop angle = 108°) of Gd-SWCNT phantom solution is 14 times greater than the Gd-based clinical MRI contrast agent Magnevist. Additionally, these nanotubes exhibit near infrared fluorescence with distinct E11 transitions of several semiconducting SWCNTs. Taken together, these results demonstrate that Gd-SWCNTs have potential as a novel, highly efficacious, multimodal MRI-NIR optical imaging contrast agent.

A highly stable gadolinium complex with a fast, associative mechanism of water exchange.

PubMed

Thompson, Marlon K; Botta, Mauro; Nicolle, Gaëlle; Helm, Lothar; Aime, Silvio; Merbach, André E; Raymond, Kenneth N

2003-11-26

The stability and water exchange dynamics of gadolinium (GdIII) complexes are critical characteristics that determine their effectiveness as contrast agents for magnetic resonance imaging (MRI). A new heteropodal GdIII chelate, [Gd-TREN-bis(6-Me-HOPO)-(TAM-TRI)(H2O)2] (Gd-2), is presented which is based on a hydroxypyridinate (HOPO)-terephthalamide (TAM) ligand design. Thermodynamic equilibrium constants for the acid-base properties and the GdIII complexation strength of TREN-bis(6-Me-HOPO)-(TAM-TRI) (2) were measured by potentiometric and spectrophotometric titration techniques, respectively. The pGd of 2 is 20.6 (pH 7.4, 25 degrees C, I = 0.1 M), indicating that Gd-2 is of more than sufficient thermodynamic stability for in vivo MRI applications. The water exchange rate of Gd-2 (kex = 5.3(+/-0.6) x 107 s-1) was determined by variable temperature 17O NMR and is in the fast exchange regime - ideal for MRI. Variable pressure 17O NMR was used to determine the volume of activation (DeltaV) of Gd-2. DeltaV for Gd-2 is -5 cm3 mol-1, indicative of an interchange associative (Ia) water exchange mechanism. The results reported herein are important as they provide insight into the factors influencing high stability and fast water exchange in the HOPO series of complexes, potentially future clinical contrast agents.

A sodium gadolinium phosphate with two different types of tunnel structure: Synthesis, crystal structure, and optical properties of Na 3GdP 2O 8

NASA Astrophysics Data System (ADS)

Fang, M.; Cheng, W.-D.; Zhang, H.; Zhao, D.; Zhang, W.-L.; Yang, S.-L.

2008-09-01

A sodium gadolinium phosphate crystal, Na 3GdP 2O 8, has been synthesized by a high-temperature solution reaction, and it exhibits a new structural family of the alkali-metal-rare-earth phosphate system. Although many compounds with formula M 3LnP 2O 8 have been reported, but they were shown to be orthorhombic [R. Salmon, C. Parent, M. Vlasse, G. LeFlem, Mater. Res. Bull. 13 (1978) 439] rather than monoclinic as shown in this paper. Single-crystal X-ray diffraction analysis shows the structure to be monoclinic with space group C2/ c and the cell parameters: a=27.55 (25), b=5.312 (4), c=13.935(11) Å, β=91.30(1)°, and V=2038.80 Å 3, Z=4. Its structure features a three-dimensional GdP 2O 83- anionic framework with two different types of interesting tunnels at where Na atoms are located by different manners. The framework is constructed by Gd polyhedra and isolated PO 4 tetrahedra. It is different from the structure of K 3NdP 2O 8 [R. Salmon, C. Parent, M. Vlasse, G. LeFlem, Mater. Res. Bull. 13 (1978) 439] with space group P2 1/ m that shows only one type of tunnel. The emission spectrum and the absorption spectrum of the compound have been investigated. Additionally, the calculations of band structure, density of states, dielectric constants, and refractive indexes have been also performed with the density functional theory method. The obtained results tend to support the experimental data.

Anxiety and retrieval inhibition: support for an enhanced inhibition account.

PubMed

Nuñez, Mia; Gregory, Josh; Zinbarg, Richard E

2017-02-01

Retrieval inhibition of negative associations is important for exposure therapy for anxiety, but the relationship between memory inhibition and anxiety is not well understood-anxiety could either be associated with enhanced or deficient inhibition. The present study tested these two competing hypotheses by measuring retrieval inhibition of negative stimuli by related neutral stimuli. Non-clinically anxious undergraduates completed measures of trait and state anxiety and completed a retrieval induced forgetting task. Adaptive forgetting varied with state anxiety. Low levels of state anxiety were associated with no evidence for retrieval inhibition for either threatening or non-threatening categories. Participants in the middle tertile of state anxiety scores exhibited retrieval inhibition for non-threatening categories but not for threatening categories. Participants in the highest tertile of state anxiety, however, exhibited retrieval inhibition for both threatening and non-threatening categories with the magnitude of retrieval inhibition being greater for threatening than non-threatening categories. The data are in line with the avoidance aspect of the vigilance-avoidance theory of anxiety and inhibition. Implications for cognitive behavioural therapy practices are discussed.

Effect of dimethyl sulfoxide on inhibition of post-ovariectomy osteopenia in rats.

PubMed

Tamjidipoor, Ahmad; Tavafi, Majid; Ahmadvand, Hasan

2013-01-01

There is increasing evidence that oxidative stress, due to estrogen deficiency, leads to osteopenia. In this study, dimethyl sulfoxide (DMSO), an antioxidant solvent, was used against post-ovariectomy osteopenia (PO) in rats. Forty female rats were divided into 5 groups randomly as follows: Sham, control group; OVX, ovariectomized group; DMSO1, ovariectomized injected DMSO (0.5 ml/kg/d ip); DMSO2, ovariectomized injected DMSO (1 ml/kg/day ip) and DMSO3, ovariectomized injected DMSO (2 ml/kg/d ip). DMSO therapy started 1 week after ovariectomy and continued for 13 weeks. After 13th weeks, sera were prepared, and then L4 vertebrae and right tibial bones rinsed in fixative. Serum bone alkaline phosphatase (BALP), osteocalcin, pyridinoline, malondialdehyde (MDA) and glutathione (GSH) were measured. Trabecular volume density, trabecular and cortex thickness were estimated. Osteoclast and osteoblast numbers were counted morphometrically. The data were analyzed by ANOVA and then post hoc Tukey test at p < 0.05. The increase of pyridinoline and decrease of BALP in DMSO injected groups were inhibited compared with OVX group (p < 0.05). In DMSO injected groups, decrease of bone density, trabecular volume density, thickness of trabecular and tibial cortex were inhibited compared with OVX group (p < 0.05). MDA decreased significantly in DMSO injected groups compared with OVX group. Osteoclast number decreased in DMSO injected groups compared with OVX group (p < 0.05). Osteoblast number did not show significant change in DMSO groups compared with OVX group. In conclusion, DMSO ameliorates PO through decrease of osteoclast number, osteoclast inhibition and osteoblast activation. These effects may probably be mediated via antioxidant property of DMSO.

Polysulfonate suramin inhibits Zika virus infection.

PubMed

Tan, Chee Wah; Sam, I-Ching; Chong, Wei Lim; Lee, Vannajan Sanghiran; Chan, Yoke Fun

2017-07-01

Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition. Suramin, an FDA-approved anti-parasitic drug, inhibits ZIKV infection with 3-5 log 10  PFU viral reduction with IC 50 value of ∼2.5-5 μg/ml (1.93 μM-3.85 μM). A time-of-drug-addition study revealed that suramin remains potent even when administrated at 1-24 hpi. Suramin inhibits ZIKV infection by preventing viral adsorption, entry and replication. Molecular dynamics simulation revealed stronger interaction of suramin with ZIKV NS3 helicase than with the envelope protein. Suramin warrants further investigation as a potential antiviral candidate for ZIKV infection. Heparan sulfate (HS) is a cellular attachment receptor for multiple flaviviruses. However, no direct ZIKV-heparin interaction was observed in heparin-binding analysis, and downregulate or removal of cellular HS with sodium chlorate or heparinase I/III did not inhibit ZIKV infection. This indicates that cell surface HS is not utilized by ZIKV as an attachment receptor. Copyright © 2017 Elsevier B.V. All rights reserved.

CHILDHOOD MALTREATMENT PREDICTS REDUCED INHIBITION-RELATED ACTIVITY IN THE ROSTRAL ANTERIOR CINGULATE IN PTSD, BUT NOT TRAUMA-EXPOSED CONTROLS.

PubMed

Stevens, Jennifer S; Ely, Timothy D; Sawamura, Takehito; Guzman, Dora; Bradley, Bekh; Ressler, Kerry J; Jovanovic, Tanja

2016-07-01

A deficit in the ability to inhibit fear has been proposed as a biomarker of posttraumatic stress disorder (PTSD). Previous research indicates that individuals with PTSD show reduced inhibition-related activation in rostral anterior cingulate cortex (rACC). The goal of the current study was to investigate differential influences of an early environmental risk factor for PTSD-childhood maltreatment-on inhibition-related brain function in individuals with PTSD versus trauma-exposed controls. Individuals with PTSD (n = 37) and trauma-exposed controls (n = 53) were recruited from the primary care waiting rooms of an urban public hospital in Atlanta, GA. Participants completed an inhibition task during fMRI, and reported childhood and adult traumatic experiences. The groups were matched for adult and child trauma load. We observed an interaction between childhood maltreatment severity and PTSD status in the rACC (P < .05, corrected), such that maltreatment was negatively associated with inhibition-related rACC activation in the PTSD group, but did not influence rACC activation in the TC group. Rostral ACC activation was associated with inhibition-related task performance in the TC group but not the PTSD group, suggesting a possible contribution to stress resilience. Findings highlight individual differences in neural function following childhood trauma, and point to inhibition-related activation in rostral ACC as a risk factor for PTSD. © 2016 Wiley Periodicals, Inc.

Modified Wideband Three-Dimensional Late Gadolinium Enhancement MRI for Patients with Implantable Cardiac Devices

PubMed Central

Rashid, Shams; Rapacchi, Stanislas; Shivkumar, Kalyanam; Plotnik, Adam; Finn, J. Paul; Hu, Peng

2015-01-01

Purpose To study the effects of cardiac devices on three-dimensional (3D) late gadolinium enhancement (LGE) MRI and to develop a 3D LGE protocol for implantable cardioverter defibrillator (ICD) patients with reduced image artifacts. Theory and Methods The 3D LGE sequence was modified by implementing a wideband inversion pulse, which reduces hyperintensity artifacts, and by increasing bandwidth of the excitation pulse. The modified wideband 3D LGE sequence was tested in phantoms and evaluated in six volunteers and five patients with ICDs. Results Phantom and in vivo studies results demonstrated extended signal void and ripple artifacts in 3D LGE that were associated with ICDs. The reason for these artifacts was slab profile distortion and the subsequent aliasing in the slice-encoding direction. The modified wideband 3D LGE provided significantly reduced ripple artifacts than 3D LGE with wideband inversion only. Comparison of 3D and 2D LGE images demonstrated improved spatial resolution of the heart using 3D LGE. Conclusion Increased bandwidth of the inversion and excitation pulses can significantly reduce image artifacts associated with ICDs. Our modified wideband 3D LGE protocol can be readily used for imaging patients with ICDs given appropriate safety guidelines are followed. PMID:25772155

Inhibited attachment behaviour and disinhibited social engagement behaviour as relevant concepts in referred home reared children.

PubMed

Scheper, F Y; Abrahamse, M E; Jonkman, C S; Schuengel, C; Lindauer, R J L; de Vries, A L C; Doreleijers, T A H; Jansen, L M C

2016-07-01

Disorders of attachment and social engagement have mainly been studied in children, reared in institutions and foster care. There are few studies amongst home reared children living with biological parents. The aim of this study was to test the clinical significance of inhibited attachment behaviour and disinhibited social engagement behaviour in young home reared children, referred for treatment of emotional and behavioural problems, compared with young children in treatment foster care. The Disturbances of Attachment Interview, Maltreatment Classification System, the Child Behaviour Checklist and Parenting Stress Index were used in 141 referred home reared children and 59 referred foster children, aged 2.0-7.9 years (M = 4.7, SE = 1.3), 71% boys. Inhibited attachment behaviour was less prevalent in the referred home reared group (9%) than in the foster care group (27%). Disinhibited social engagement behaviour was found in 42% of the home reared group, similar to the foster care group. Inhibited attachment behaviour and disinhibited social engagement behaviour were not associated with child maltreatment. More inhibited attachment behaviour was associated with clinical levels of child internalizing and externalizing behaviour in the home reared group, not in the foster care group. In both groups, more disinhibited social engagement behaviour was associated with clinical levels of externalizing behaviour and with more parenting stress. Even without evident links to maltreatment, results of this study suggest clinical significance of inhibited attachment behaviour and disinhibited social engagement behaviour in young home reared children referred for treatment of emotional and behavioural problems. © 2016 John Wiley & Sons Ltd.

Inhibition.

ERIC Educational Resources Information Center

Kupperman, Joel J.

1978-01-01

Explores the use of the concept of inhibition in moral philosophy. Argues that there are strong practical reasons for basing moral teaching on simple moral rules and for inculcating inhibitions about breaking these rules. (Author)

Inhibition of Group I Metabotropic Glutamate Receptors Reverses Autistic-Like Phenotypes Caused by Deficiency of the Translation Repressor eIF4E Binding Protein 2

PubMed Central

Aguilar-Valles, Argel; Matta-Camacho, Edna; Khoutorsky, Arkady; Gkogkas, Christos; Nader, Karim

2015-01-01

Exacerbated mRNA translation during brain development has been linked to autism spectrum disorders (ASDs). Deletion of the eukaryotic initiation factor 4E (eIF4E)-binding protein 2 gene (Eif4ebp2), encoding the suppressor of mRNA translation initiation 4E-BP2, leads to an imbalance in excitatory-to-inhibitory neurotransmission and ASD-like behaviors. Inhibition of group I metabotropic glutamate receptors (mGluRs) mGluR1 and mGluR5 reverses the autistic phenotypes in several ASD mouse models. Importantly, these receptors control synaptic physiology via activation of mRNA translation. We investigated the potential reversal of autistic-like phenotypes in Eif4ebp2−/− mice by using antagonists of mGluR1 (JNJ16259685) or mGluR5 (fenobam). Augmented hippocampal mGluR-induced long-term depression (LTD; or chemically induced mGluR-LTD) in Eif4ebp2−/− mice was rescued by mGluR1 or mGluR5 antagonists. While rescue by mGluR5 inhibition occurs through the blockade of a protein synthesis-dependent component of LTD, normalization by mGluR1 antagonists requires the activation of protein synthesis. Synaptically induced LTD was deficient in Eif4ebp2−/− mice, and this deficit was not rescued by group I mGluR antagonists. Furthermore, a single dose of mGluR1 (0.3 mg/kg) or mGluR5 (3 mg/kg) antagonists in vivo reversed the deficits in social interaction and repetitive behaviors (marble burying) in Eif4ebp2−/− mice. Our results demonstrate that Eif4ebp2−/− mice serve as a relevant model to test potential therapies for ASD symptoms. In addition, we provide substantive evidence that the inhibition of mGluR1/mGluR5 is an effective treatment for physiological and behavioral alterations caused by exacerbated mRNA translation initiation. SIGNIFICANCE STATEMENT Exacerbated mRNA translation during brain development is associated with several autism spectrum disorders (ASDs). We recently demonstrated that the deletion of a negative regulator of mRNA translation initiation

Inhibition of Group I Metabotropic Glutamate Receptors Reverses Autistic-Like Phenotypes Caused by Deficiency of the Translation Repressor eIF4E Binding Protein 2.

PubMed

Aguilar-Valles, Argel; Matta-Camacho, Edna; Khoutorsky, Arkady; Gkogkas, Christos; Nader, Karim; Lacaille, Jean-Claude; Sonenberg, Nahum

2015-08-05

Exacerbated mRNA translation during brain development has been linked to autism spectrum disorders (ASDs). Deletion of the eukaryotic initiation factor 4E (eIF4E)-binding protein 2 gene (Eif4ebp2), encoding the suppressor of mRNA translation initiation 4E-BP2, leads to an imbalance in excitatory-to-inhibitory neurotransmission and ASD-like behaviors. Inhibition of group I metabotropic glutamate receptors (mGluRs) mGluR1 and mGluR5 reverses the autistic phenotypes in several ASD mouse models. Importantly, these receptors control synaptic physiology via activation of mRNA translation. We investigated the potential reversal of autistic-like phenotypes in Eif4ebp2(-/-) mice by using antagonists of mGluR1 (JNJ16259685) or mGluR5 (fenobam). Augmented hippocampal mGluR-induced long-term depression (LTD; or chemically induced mGluR-LTD) in Eif4ebp2(-/-) mice was rescued by mGluR1 or mGluR5 antagonists. While rescue by mGluR5 inhibition occurs through the blockade of a protein synthesis-dependent component of LTD, normalization by mGluR1 antagonists requires the activation of protein synthesis. Synaptically induced LTD was deficient in Eif4ebp2(-/-) mice, and this deficit was not rescued by group I mGluR antagonists. Furthermore, a single dose of mGluR1 (0.3 mg/kg) or mGluR5 (3 mg/kg) antagonists in vivo reversed the deficits in social interaction and repetitive behaviors (marble burying) in Eif4ebp2(-/-) mice. Our results demonstrate that Eif4ebp2(-/-) mice serve as a relevant model to test potential therapies for ASD symptoms. In addition, we provide substantive evidence that the inhibition of mGluR1/mGluR5 is an effective treatment for physiological and behavioral alterations caused by exacerbated mRNA translation initiation. Exacerbated mRNA translation during brain development is associated with several autism spectrum disorders (ASDs). We recently demonstrated that the deletion of a negative regulator of mRNA translation initiation, the eukaryotic initiation factor 4E

Chelating DTPA amphiphiles: ion-tunable self-assembly structures and gadolinium complexes.

PubMed

Moghaddam, Minoo J; de Campo, Liliana; Kirby, Nigel; Drummond, Calum J

2012-10-05

A series of chelating amphiphiles and their gadolinium (Gd(III)) metal complexes have been synthesized and studied with respect to their neat and lyotropic liquid crystalline phase behavior. These amphiphiles have the ability to form ion-tunable self-assembly nanostructures and their associated Gd(III) complexes have potential as magnetic resonance imaging (MRI) contrast enhancement agents. The amphiphiles are composed of diethylenetriaminepentaacetic acid (DTPA) chelates conjugated to one or two oleyl chain(s) (DTPA-MO and DTPA-BO), or isoprenoid-type chain(s) of phytanyl (DTPA-MP and DTPA-BP). The thermal phase behavior of the neat amphiphiles was examined by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and cross polarizing optical microscopy (POM). Self-assembly of neat amphiphiles and their associated Gd complexes, as well as their lyotropic phase behavior in water and sodium acetate solutions of different ionic strengths, were examined by POM and small and wide angle X-ray scattering (SWAXS). All neat amphiphiles exhibited lamellar structures. The non-complexed amphiphiles showed a variety of lyotropic phases depending on the number and nature of the hydrophobic chain in addition to the ionic state of the hydration. Upon hydration with increased Na-acetate concentration and the subtle changes in the effective headgroup size, the interfacial curvature of the amphiphile increased, altering the lyotropic liquid crystalline structures towards higher order mesophases such as the gyroid (Ia3d) bicontinuous cubic phase. The chelation of Gd with the DTPA amphiphiles resulted in lamellar crystalline structures for all the neat amphiphiles. Upon hydration with water, the Gd-complexed mono-conjugates formed micellar or vesicular self-assemblies, whilst the bis-conjugates transformed only partially into lyotropic liquid crystalline mesophases.

Microfabrication of a gadolinium-derived solid-state sensor for thermal neutrons

PubMed Central

Achyuthan, Komandoor E.; Allen, Matthew; Denton, Michele L. B.; Siegal, Michael P.; Manginell, Ronald P.

2017-01-01

Abstract Neutron sensing is critical in civilian and military applications. Conventional neutron sensors are limited by size, weight, cost, portability and helium supply. Here the microfabrication of gadolinium (Gd) conversion material–based heterojunction diodes for detecting thermal neutrons using electrical signals produced by internal conversion electrons (ICEs) is described. Films with negligible stress were produced at the tensile-compressive crossover point, enabling Gd coatings of any desired thickness by controlling the radiofrequency sputtering power and using the zero-point near p(Ar) of 50 mTorr at 100 W. Post-deposition Gd oxidation–induced spallation was eliminated by growing a residual stress-free 50 nm neodymium-doped aluminum cap layer atop Gd. The resultant coatings were stable for at least 6 years, demonstrating excellent stability and product shelf-life. Depositing Gd directly on the diode surface eliminated the air gap, leading to a 200-fold increase in electron capture efficiency and facilitating monolithic microfabrication. The conversion electron spectrum was dominated by ICEs with energies of 72, 132 and 174 keV. Results are reported for neutron reflection and moderation by polyethylene for enhanced sensitivity, and γ- and X-ray elimination for improved specificity. The optimal Gd thickness was 10.4 μm for a 300 μm-thick partially depleted diode of 300 mm2 active surface area. Fast detection (within 10 min) at a neutron source-to-diode distance of 11.7 cm was achieved with this configuration. All ICE energies along with γ-ray and Kα,β X-rays were modeled to emphasize correlations between experiment and theory. Semi-conductor thermal neutron detectors offer advantages for field-sensing of radioactive neutron sources. PMID:28369631

Neural and Behavioral Correlates of Attentional Inhibition Training and Perceptual Discrimination Training in a Visual Flanker Task

PubMed Central

Melara, Robert D.; Singh, Shalini; Hien, Denise A.

2018-01-01

Two groups of healthy young adults were exposed to 3 weeks of cognitive training in a modified version of the visual flanker task, one group trained to discriminate the target (discrimination training) and the other group to ignore the flankers (inhibition training). Inhibition training, but not discrimination training, led to significant reductions in both Garner interference, indicating improved selective attention, and in Stroop interference, indicating more efficient resolution of stimulus conflict. The behavioral gains from training were greatest in participants who showed the poorest selective attention at pretest. Electrophysiological recordings revealed that inhibition training increased the magnitude of Rejection Positivity (RP) to incongruent distractors, an event-related potential (ERP) component associated with inhibitory control. Source modeling of RP uncovered a dipole in the medial frontal gyrus for those participants receiving inhibition training, but in the cingulate gyrus for those participants receiving discrimination training. Results suggest that inhibitory control is plastic; inhibition training improves conflict resolution, particularly in individuals with poor attention skills. PMID:29875644

Neural and Behavioral Correlates of Attentional Inhibition Training and Perceptual Discrimination Training in a Visual Flanker Task.

PubMed

Melara, Robert D; Singh, Shalini; Hien, Denise A

2018-01-01

Two groups of healthy young adults were exposed to 3 weeks of cognitive training in a modified version of the visual flanker task, one group trained to discriminate the target (discrimination training) and the other group to ignore the flankers (inhibition training). Inhibition training, but not discrimination training, led to significant reductions in both Garner interference, indicating improved selective attention, and in Stroop interference, indicating more efficient resolution of stimulus conflict. The behavioral gains from training were greatest in participants who showed the poorest selective attention at pretest. Electrophysiological recordings revealed that inhibition training increased the magnitude of Rejection Positivity (RP) to incongruent distractors, an event-related potential (ERP) component associated with inhibitory control. Source modeling of RP uncovered a dipole in the medial frontal gyrus for those participants receiving inhibition training, but in the cingulate gyrus for those participants receiving discrimination training. Results suggest that inhibitory control is plastic; inhibition training improves conflict resolution, particularly in individuals with poor attention skills.

Anything goes? Regulation of the neural processes underlying response inhibition in TBI patients.

PubMed

Moreno-López, Laura; Manktelow, Anne E; Sahakian, Barbara J; Menon, David K; Stamatakis, Emmanuel A

2017-02-01

Despite evidence for beneficial use of methylphenidate in response inhibition, no studies so far have investigated the effects of this drug in the neurobiology of inhibitory control in traumatic brain injury (TBI), even though impulsive behaviours are frequently reported in this patient group. We investigated the neural basis of response inhibition in a group of TBI patients using functional magnetic resonance imaging and a stop-signal paradigm. In a randomised double-blinded crossover study, the patients received either a single 30mg dose of methylphenidate or placebo and performed the stop-signal task. Activation in the right inferior frontal gyrus (RIFG), an area associated with response inhibition, was significantly lower in patients compared to healthy controls. Poor response inhibition in this group was associated with greater connectivity between the RIFG and a set of regions considered to be part of the default mode network (DMN), a finding that suggests the interplay between DMN and frontal executive networks maybe compromised. A single dose of methylphenidate rendered activity and connectivity profiles of the patients RIFG near normal. The results of this study indicate that the neural circuitry involved in response inhibition in TBI patients may be partially restored with methylphenidate. Given the known mechanisms of action of methylphenidate, the effect we observed may be due to increased dopamine and noradrenaline levels. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

The inhibition of monoamine oxidase by phenformin and pentamidine.

PubMed

Barkhuizen, M; Petzer, A; Petzer, J P

2014-09-01

A computational study has suggested that phenformin, an oral hypoglycaemic drug, may bind to the active sites of the monoamine oxidase (MAO) A and B enzymes. The present study therefore investigates the MAO inhibitory properties of phenformin. Pentamidine, a structurally related diamidine compound, has previously been reported to be a MAO inhibitor and was included in this study as a reference compound. Using recombinant human MAO-A and MAO-B, this study finds that phenformin acts as a moderately potent MAO-A selective inhibitor with an IC50 value of 41 µM. Pentamidine, on the other hand, potently inhibits both MAO-A and MAO-B with IC50 values of 0.61 μM and 0.22 μM, respectively. An examination of the recoveries of the enzymatic activities after dilution and dialysis of the enzyme-inhibitor complexes shows that both compounds interact reversibly with the MAO enzymes. A kinetic analysis suggests that pentamidine acts as a competitive inhibitor with estimated Ki values of 0.41 μM and 0.22 μM for the inhibition of MAO-A and MAO-B, respectively. Phenformin also exhibited a competitive mode of MAO-A inhibition with an estimated Ki value of 65 µM. This study concludes that biguanide and amidine functional groups are most likely important structural features for the inhibition of the MAOs by phenformin and pentamidine, and compounds containing these and closely related functional groups should be considered as potential MAO inhibitors. Furthermore, the biguanide and amidine functional groups may act as useful moieties in the future design of MAO inhibitors. © Georg Thieme Verlag KG Stuttgart · New York.

Atorvastatin inhibits insulin synthesis by inhibiting the Ras/Raf/ERK/CREB pathway in INS-1 cells

PubMed Central

Sun, Hongxi; Li, Yu; Sun, Bei; Hou, Ningning; Yang, Juhong; Zheng, Miaoyan; Xu, Jie; Wang, Jingyu; Zhang, Yi; Zeng, Xianwei; Shan, Chunyan; Chang, Bai; Chen, Liming; Chang, Baocheng

2016-01-01

Abstract Backround: Type 2 diabetes has become a global epidemic disease. Atorvastatin has become a cornerstone in the prevention and treatment of atherosclerosis. However, increasing evidence showed that statins can dose-dependently increase the risk of diabetes mellitus. The mechanism is not clear. Objective: The Ras complex pathway (Ras/Raf/extracellular signal-regulated kinase [ERK]/cAMP response element-binding protein [CREB]) is the major pathway that regulates the gene transcription. Except for the inhibition of cholesterol synthesis by inhibiting the 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-COA) reductase, statins can also downregulate the phosphorylation of a series of downstream substrates including the key proteins of the Ras complex pathway, therefore may inhibit the insulin syntheses in pancreatic beta cells. In our study, we investigated the inhibitory effect and the underlying mechanism of atorvastatin on insulin synthesis in rat islets. Methods: Islets were isolated from Wistar rats and cultured in Roswell Park Memorial Institute (RPMI)-1640 medium. The insulin content in the medium was measured by radioimmunoassay before and after the treatment of 50 μM atorvastatin. Effect of atorvastatin on the expression of insulin message Ribonucleic acid (mRNA) in pancreatic islet beta cells was also detected using quantitative real-time polymerase chain reaction. Western blotting was used to explore the possible role of the Ras complex pathway (Ras/Raf/ERK/CREB) in atorvastatin-inhibited insulin synthesis. The effects of atorvastatin on the binding of nuclear transcription factor p-CREB with CRE in INS-1 cells were examined via chromatin immunoprecipitation assay. Results: Compared with the control group, the insulin level decreased by 27.1% at 24 hours after atorvastatin treatment. Atorvastatin inhibited insulin synthesis by decreasing insulin mRNA expression of pancreatic islet beta cells. The activities of Ras, Raf-1, and p-CREB in the Ras complex

A meta-analytic review of collaborative inhibition and postcollaborative memory: Testing the predictions of the retrieval strategy disruption hypothesis.

PubMed

Marion, Stéphanie B; Thorley, Craig

2016-11-01

The retrieval strategy disruption hypothesis (Basden, Basden, Bryner, & Thomas, 1997) is the most widely cited theoretical explanation for why the memory performance of collaborative groups is inferior to the pooled performance of individual group members remembering alone (i.e., collaborative inhibition). This theory also predicts that several variables will moderate collaborative inhibition. This meta-analysis tests the veracity of the theory by systematically examining whether or not these variables do moderate the presence and strength of collaborative inhibition. A total of 75 effect sizes from 64 studies were included in the analysis. Collaborative inhibition was found to be a robust effect. Moreover, it was enhanced when remembering took place in larger groups, when uncategorized content items were retrieved, when group members followed free-flowing and free-order procedures, and when group members did not know one another. These findings support the retrieval strategy disruption hypothesis as a general theoretical explanation for the collaborative inhibition effect. Several additional analyses were also conducted to elucidate the potential contributions of other cognitive mechanisms to collaborative inhibition. Some results suggest that a contribution of retrieval inhibition is possible, but we failed to find any evidence to suggest retrieval blocking and encoding specificity impact upon collaborative inhibition effects. In a separate analysis (27 effect sizes), moderating factors of postcollaborative memory performance were examined. Generally, collaborative remembering tends to benefit later individual retrieval. Moderator analyses suggest that reexposure to study material may be partly responsible for this postcollaborative memory enhancement. Some applied implications of the meta-analyses are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Dual modal ultra-bright nanodots with aggregation-induced emission and gadolinium-chelation for vascular integrity and leakage detection.

PubMed

Feng, Guangxue; Li, Jackson Liang Yao; Claser, Carla; Balachander, Akhila; Tan, Yingrou; Goh, Chi Ching; Kwok, Immanuel Weng Han; Rénia, Laurent; Tang, Ben Zhong; Ng, Lai Guan; Liu, Bin

2018-01-01

The study of blood brain barrier (BBB) functions is important for neurological disorder research. However, the lack of suitable tools and methods has hampered the progress of this field. Herein, we present a hybrid nanodot strategy, termed AIE-Gd dots, comprising of a fluorogen with aggregation-induced emission (AIE) characteristics as the core to provide bright and stable fluorescence for optical imaging, and gadolinium (Gd) for accurate quantification of vascular leakage via inductively-coupled plasma mass spectrometry (ICP-MS). In this report, we demonstrate that AIE-Gd dots enable direct visualization of brain vascular networks under resting condition, and that they form localized punctate aggregates and accumulate in the brain tissue during experimental cerebral malaria, indicative of hemorrhage and BBB malfunction. With its superior detection sensitivity and multimodality, we hereby propose that AIE-Gd dots can serve as a better alternative to Evans blue for visualization and quantification of changes in brain barrier functions. Copyright © 2017. Published by Elsevier Ltd.

Changes in Signal Intensity of the Dentate Nucleus and Globus Pallidus in Pediatric Patients: Impact of Brain Irradiation and Presence of Primary Brain Tumors Independent of Linear Gadolinium-based Contrast Agent Administration.