The standardization methods of radioactive sources (125I, 131I, 99mTc, and 18F) for calibrating nuclear medicine equipment in Indonesia

NASA Astrophysics Data System (ADS)

Wurdiyanto, G.; Candra, H.

2016-03-01

The standardization of radioactive sources (125I, 131I, 99mTc and 18F) to calibrate the nuclear medicine equipment had been carried out in PTKMR-BATAN. This is necessary because the radioactive sources used in the field of nuclear medicine has a very short half-life in other that to obtain a quality measurement results require special treatment. Besides that, the use of nuclear medicine techniques in Indonesia develop rapidly. All the radioactive sources were prepared by gravimetric methods. Standardization of 125I has been carried out by photon- photon coincidence methods, while the others have been carried out by gamma spectrometry methods. The standar sources are used to calibrate a Capintec CRC-7BT radionuclide calibrator. The results shows that calibration factor for Capintec CRC-7BT dose calibrator is 1,03; 1,02; 1,06; and 1,04 for 125I, 131I, 99mTc and 18F respectively, by about 5 to 6% of the expanded uncertainties.

Measurement of excitation functions of helion-induced reactions on enriched Ru targets for production of medically important 103Pd and 101mRh and some other radionuclides.

PubMed

Skakun, Ye; Qaim, S M

2008-05-01

Excitation functions were determined by the stacked-foil and induced radioactivity measurement technique for the reactions (100)Ru(alpha,n)(103)Pd, (101)Ru(alpha,2n)(103)Pd, (101)Ru((3)He,n)(103)Pd, and (102)Ru((3)He,2n)(103)Pd, producing the therapeutic radionuclide (103)Pd, and for the reactions (101)Ru((3)He,x)(101 m)Rh(Cum) and (102)Ru((3)He,x)(101 m)Rh(Cum), producing the medically interesting radionuclide (101 m)Rh. Data were also measured for the reactions (101)Ru((3)He,pn+d)(102 m,g)Rh, (102)Ru((3)He,p2n+dn+t)(102 m,g)Rh, (101)Ru((3)He,x)(101 g)Rh(Cum), (102)Ru((3)He,x)(101 g)Rh(Cum), (101)Ru((3)He,3n)(101)Pd, (102)Ru((3)He,4n)(101)Pd, (101)Ru((3)He,4n)(100)Pd, and (101)Ru((3)He,p3n+d2n+tn)(100)Rh, producing other palladium and rhodium isotopes/isomers. The energy ranges covered were up to 25 MeV for alpha-particles and up to 34 MeV for (3)He ions. The radioactivity of the radionuclide (103)Pd induced in thin metallic foils of the enriched ruthenium isotopes was measured by high-resolution X-ray spectrometry and the radioactivities of other radionuclides by gamma-ray spectrometry. The integral thick target yields of the radionuclide (103)Pd calculated from the excitation functions of the first four of the above-named reactions amount to 960, 1050, 50, and 725 kBq/microAh, respectively, at the maximum investigated energies of the incident particles. The integral thick target yields of the radionuclide (101 m)Rh amount to 16.1 and 2.9 MBq/microAh for (101)Ru and (102)Ru targets, respectively, at 34 MeV energy of incident (3)He ions. The integral yields of the other observed radionuclides were also deduced from the excitation functions of the above-mentioned respective nuclear reactions. The excitation functions and integral yields of some rare reaction products were also determined. The experimental excitation functions of some reactions are compared with the predictions of nuclear model calculations. In general, good agreement was obtained.

Impurities in Tc-99m radiopharmaceutical solution obtained from Mo-100 in cyclotron.

PubMed

Tymiński, Zbigniew; Saganowski, Paweł; Kołakowska, Ewa; Listkowska, Anna; Ziemek, Tomasz; Cacko, Daniel; Dziel, Tomasz

2018-04-01

The gamma emitting impurities in 99m Tc solution obtained from enriched molybdenum 100 Mo metallic target after its irradiation in a cyclotron were measured using a high-purity germanium (HPGe) detector. The radioactivity range of tested samples of 99m Tc was rather low, in the range from 0.34 to 2.39 MBq, thus creating a challenge to investigate the standard measurement HPGe system for impurity detection and quantification. In the process of 99m Tc separation from irradiated target the AnaLig® Tc-02 resin, Dionex H + and Alumina A columns were used. Fractions of eluates from various steps of separation process were taken and measured for radionuclidic purity. The overall measurement sensitivity of gamma emitters in terms of minimum detectable activity (MDA) was found at the level of 14-70Bq with emission lines in range of 36 - 1836keV resulting in impurity content range of 6.7 × 10 -4 to 3.4 × 10 -3 % for 93 Tc, 93m Tc, 94 Tc, 94m Tc, 95 Tc, 95m Tc, 96 Tc 96 Nb, 97 Nb, 99 Mo contaminants and 9.4 × 10 -3 % for 97m Tc. The usefulness of the chosen measurement conditions and the method applied to testing the potential contaminators was proved by reaching satisfactory results of MDAs less than the criteria of impurity concentration of all nuclides specified in the European Pharmacopoeia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Determination of the intrinsic energy dependence of LiF:Mg,Ti thermoluminescent dosimeters for 125I and 103Pd brachytherapy sources relative to 60Co.

PubMed

Reed, J L; Rasmussen, B E; Davis, S D; Micka, J A; Culberson, W S; DeWerd, L A

2014-12-01

To determine the intrinsic energy dependence of LiF:Mg,Ti thermoluminescent dosimeters (TLD-100) for (125)I and (103)Pd brachytherapy sources relative to (60)Co. LiF:Mg,Ti TLDs were irradiated with low-energy brachytherapy sources and with a (60)Co teletherapy source. The brachytherapy sources measured were the Best 2301 (125)I seed, the OncoSeed 6711 (125)I seed, and the Best 2335 (103)Pd seed. The TLD light output per measured air-kerma strength was determined for the brachytherapy source irradiations, and the TLD light output per air kerma was determined for the (60)Co irradiations. Monte Carlo (MC) simulations were used to calculate the dose-to-TLD rate per air-kerma strength for the brachytherapy source irradiations and the dose to TLD per air kerma for the (60)Co irradiations. The measured and MC-calculated results for all irradiations were used to determine the TLD intrinsic energy dependence for (125)I and (103)Pd relative to (60)Co. The relative TLD intrinsic energy dependences (relative to (60)Co) and associated uncertainties (k = 1) were determined to be 0.883 ± 1.3%, 0.870 ± 1.4%, and 0.871 ± 1.5% for the Best 2301 seed, OncoSeed 6711 seed, and Best 2335 seed, respectively. The intrinsic energy dependence of TLD-100 is dependent on photon energy, exhibiting changes of 13%-15% for (125)I and (103)Pd sources relative to (60)Co. TLD measurements of absolute dose around (125)I and (103)Pd brachytherapy sources should explicitly account for the relative TLD intrinsic energy dependence in order to improve dosimetric accuracy.

The absorbed dose to blood from blood-borne activity

NASA Astrophysics Data System (ADS)

Hänscheid, H.; Fernández, M.; Lassmann, M.

2015-01-01

The radiation absorbed dose to blood and organs from activity in the blood is relevant for nuclear medicine dosimetry and for research in biodosimetry. The present study provides coefficients for the average absorbed dose rates to the blood from blood-borne activity for radionuclides frequently used in targeted radiotherapy and in PET diagnostics. The results were deduced from published data for vessel radius-dependent dose rate coefficients and reasonable assumptions on the blood-volume distribution as a function of the vessel radius. Different parts of the circulatory system were analyzed separately. Vessel size information for heart chambers, aorta, vena cava, pulmonary artery, and capillaries was taken from published results of morphometric measurements. The remaining blood not contained in the mentioned vessels was assumed to reside in fractal-like vascular trees, the smallest branches of which are the arterioles or venules. The applied vessel size distribution is consistent with recommendations of the ICRP on the blood-volume distribution in the human. The resulting average absorbed dose rates to the blood per nuclear disintegration per milliliter (ml) of blood are (in 10-11 Gy·s-1·Bq-1·ml) Y-90: 5.58, I-131: 2.49, Lu-177: 1.72, Sm-153: 2.97, Tc-99m: 0.366, C-11: 4.56, F-18: 3.61, Ga-68: 5.94, I-124: 2.55. Photon radiation contributes 1.1-1.2·10-11 Gy·s-1·Bq-1·ml to the total dose rate for positron emitters but significantly less for the other nuclides. Blood self-absorption of the energy emitted by ß-particles in the whole blood ranges from 37% for Y-90 to 80% for Tc-99m. The correspondent values in vascular trees, which are important for the absorbed dose to organs, range from 30% for Y-90 to 82% for Tc-99m.

Single-Crystal Bismuth Iodide Gamma-Ray Spectrometers

DTIC Science & Technology

2012-02-01

the density of the crystal (g/cm\\ M is the molecular weight of the vapor (g/mole), and R is the gas constant (cai/(K·mole)). Equation (6) indicates...along the vertical axis with a fixed rate. This simulated the downward movement of the ampoule in the conventional vertical Bridgman method. The...3cl512 1.03 4512 4.6 961 Pd Pd3d 336.5 Pd 3d512 1.03 6796 4.6 1477 Pdb N3d 340.3 Pd 3d3J2 1.03 2978 4.6 647 Pd Pd3d 341.7 Pd 3d3J2 1.03 4486 4.6 975

Biodistribution and pharmacokinetics of the (99m)Tc labeled human elastase inhibitor, elafin, in rats.

PubMed

Kaschwich, Mark; Lützen, Ulf; Zhao, Yi; Tjiong, Angelina; Marx, Marlies; Haenisch, Sierk; Wiedow, Oliver; Preuss, Stefanie; Culman, Juraj; Zuhayra, Maaz

2016-04-01

Elafin is a potent reversible inhibitor of the pro-inflammatory proteases leukocyte elastase and protease 3. It is currently in clinical development for the use in postoperative inflammatory diseases. We investigated the pharmacokinetics of (99m)Tc-labeled elafin ((99m)Tc-Elafin) in blood and individual organs in rat after bolus intravenous injection using the single photon emission tomography (SPECT). (99m)Tc-Elafin predominantly accumulated in the kidney reaching a maximum of 8.5% ± 0.1% of the injected dose per gram (ID/g) at 5 min post injection (p.i) and decreased only slowly during 24 h. In contrast, the initially high radio activity recorded in the other organs rapidly decreased parallel to the radioactivity detected in blood. The blood kinetics fits to a two compartment kinetics model. The radio activity in the dissected kidney was 4.98 ± 1.24%ID/g 24 h p.i, while in other organs, including the brain, no accumulation of (99m)Tc-Elafin was detected. At this time point 30% of the detected radioactivity in the kidney was identified to be not metabolized (99m)Tc-Elafin. In conclusion, the blood and organ-specific kinetic data provide a basis for planning of adequate dosing regimens and the high accumulation of intact elafin in the kidney favors clinical developments targeting inflammatory kidney diseases, such as chronic allograft nephropathy after kidney transplantation. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

All Prime Contract Awards by State or Country, Place, and Contractor. Part 14 (Akron, New York-Wilson, North Carolina)

DTIC Science & Technology

1990-01-01

i4 i-N( 000U or- L-4ɘ 0-4 0- ɘin L-- )CO 1-00 V) 11 034 Was00 Mtn0 40 00 (90 NO inO -400 -100 ,-411 I.1 . : I Iz o I of 103 - 110 nin I -4 -I 0 in w...4 U- 103 (0< If 0 0 0000 00000000 0 00 00000000 0 : ID ::O4I 00 00 000400 000000000 00 0. ~0 000000000o 0M If M (40 < I-4 4 14 44 .. ൴ -4-4 -i1--i -4...xzz xzzzzzzz MO) :: ax ZZ OZZZZ* a) z o z Q)Zzzz* 4)z O)zz* wzzzzzzz I moo it Z z z Z z I z z z 4D I moo 11 0) QC>00 11 cn a a) PD In In ",4 *4D-qamr-m

Spent fuel reaction - the behavior of the {epsilon}-phase over 3.1 years

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

Finn, P.A.; Hoh, J.C.; Wolf, S.F.

The release fractions of the five elements in the {epsilon}-phase ({sup 99}Tc, {sup 97}Mo, Ru, Rh, and Pd) as well as that of {sup 238}U are reported for the reaction of two oxide fuels (ATM-103 and ATM-106) in unsaturated tests under oxidizing conditions. The {sup 99}Tc release fractions provide a lower limit for the magnitude of the spent fuel reaction. The {sup 99}Tc release fractions indicate that a surface reaction might be the rate controlling mechanism for fuel reaction under unsaturated conditions and the oxidant is possibly H{sub 2}O{sub 2}, a product of alpha radiolysis of water.

Patient-reported health-related quality of life for men treated with low-dose-rate prostate brachytherapy as monotherapy with 125-iodine, 103-palladium, or 131-cesium: Results of a prospective phase II study.

PubMed

Blanchard, Pierre; Pugh, Thomas J; Swanson, David A; Mahmood, Usama; Chen, Hsiang-Chun; Wang, Xuemei; Graber, William J; Kudchadker, Rajat J; Bruno, Teresa; Feeley, Thomas; Frank, Steven J

To compare quality of life (QoL) after brachytherapy with one of the three approved radioactive isotopes. Patients with mostly favorable intermediate-risk prostate cancer were treated on this prospective phase II trial with brachytherapy as monotherapy, without hormonal therapy. QoL was recorded at baseline and each follow-up by using the Expanded Prostate Cancer Index Composite instrument. The minimal clinically important difference was defined as half the standard deviation of the baseline score for each domain. Mixed effect models were used to compare the different isotopes, and time-driven activity-based costing was used to compute costs. From 2006 to 2013, 300 patients were treated with iodine-125 (I-125, n = 98, prescribed dose [PD] = 145 Gy), palladium-103 (Pd-103, n = 102, PD = 125 Gy), or cesium-131 (Cs-131, n = 100, PD = 115 Gy). Median age was 64.9 years. Median follow-up time was 5.1 years for the entire cohort, and 7.1, 4.8 and 3.3 years for I-125, Pd-103, and Cs-131 groups, respectively. All three isotope groups showed an initial drop in QoL at first follow-up, which gradually improved over the first 2 years for urinary and bowel domains. QoL profiles were similar between I-125 and Pd-103, whereas Cs-131 showed a statistically significant decrease in QoL regarding bowel and sexual function at 12 months compared with Pd-103. However, these differences did not reach the minimal clinically important difference. Compared with I-125, the use of Pd-103 or Cs-131 resulted in cost increases of 18% and 34% respectively. The three different isotopes produced a similar QoL profile. Statistically significant differences favored Pd-103/I-125 over Cs-131 for bowel and sexual QoL, but this did not reach clinical significance. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Periodontal disease and breast cancer: Prospective cohort study of postmenopausal women

PubMed Central

Freudenheim, Jo L; Genco, Robert J; LaMonte, Michael J; Millen, Amy E; Hovey, Kathleen M; Mai, Xiaodan; Nwizu, Ngozi; Andrews, Christopher A; Wactawski-Wende, Jean

2015-01-01

Background Periodontal disease (PD) has been consistently associated with chronic disease; there are no large studies of breast cancer although oral-associated microbes are present in breast tumors. Methods In the Women’s Health Initiative Observational Study, a prospective cohort of postmenopausal women, 73,737 women without previous breast cancer were followed. Incident, primary, invasive breast tumors were verified by physician adjudication. PD was by self-report. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox proportional hazards, adjusted for breast cancer risk factors. Because the oral microbiome of those with PD differs with smoking status, we examined associations stratified by smoking. Results 2,124 incident, invasive breast cancer cases were identified after mean follow-up of 6.7 years. PD, reported by 26.1% of women, was associated with increased breast cancer risk (HR 1.14, 95% CI 1.03 to 1.26), particularly among former smokers who quit within 20 years (HR 1.36; 95% CI 1.05 to 1.77). Among current smokers, the trend was similar (HR 1.32; 95% CI 0.83 to 2.11); there were few cases (n=74) and the CI included the null. The population attributable fraction was 12.06% (95% CI 1.12 to 21.79) and 10.90% (95% CI 10.31 to 28.94) for PD among former smokers quitting within 20 years and current smokers, respectively. Conclusion PD, a common chronic inflammatory disorder, was associated with increased risk of postmenopausal breast cancer, particularly among former smokers who quit in the past 20 years. Impact Understanding a possible role of the oral microbiome in breast carcinogenesis could impact prevention. PMID:26689418

Theobroma cacao cystatins impair Moniliophthora perniciosa mycelial growth and are involved in postponing cell death symptoms.

PubMed

Pirovani, Carlos Priminho; da Silva Santiago, André; dos Santos, Lívia Santana; Micheli, Fabienne; Margis, Rogério; da Silva Gesteira, Abelmon; Alvim, Fátima Cerqueira; Pereira, Gonçalo Amarante Guimarães; de Mattos Cascardo, Júlio Cézar

2010-11-01

Three cystatin open reading frames named TcCys1, TcCys2 and TcCys3 were identified in cDNA libraries from compatible interactions between Theobroma cacao (cacao) and Moniliophthora perniciosa. In addition, an ORF named TcCys4 was identified in the cDNA library of the incompatible interaction. The cDNAs encoded conceptual proteins with 209, 127, 124, and 205 amino acid residues, with a deduced molecular weight of 24.3, 14.1, 14.3 and 22.8 kDa, respectively. His-tagged recombinant proteins were purified from Escherichia coli expression, and showed inhibitory activities against M. perniciosa. The four recombinant cystatins exhibited K(i) values against papain in the range of 152-221 nM. Recombinant TcCYS3 and TcCYS4 immobilized in CNBr-Sepharose were efficient to capture M. perniciosa proteases from culture media. Polyclonal antibodies raised against the recombinant TcCYS4 detected that the endogenous protein was more abundant in young cacao tissues, when compared with mature tissues. A ~85 kDa cacao multicystatin induced by M. perniciosa inoculation, MpNEP (necrosis and ethylene-inducing protein) and M. perniciosa culture supernatant infiltration were detected by anti-TcCYS4 antibodies in cacao young tissues. A direct role of the cacao cystatins in the defense against this phytopathogen was proposed, as well as its involvement in the development of symptoms of programmed cell death.

Measurement of activation cross-section of long-lived products in deuteron induced nuclear reactions on palladium in the 30-50MeV energy range.

PubMed

Ditrói, F; Tárkányi, F; Takács, S; Hermanne, A; Ignatyuk, A V

2017-10-01

Excitation functions were measured in the 31-49.2MeV energy range for the nat Pd(d,xn) 111,110m,106m,105,104g,103 Ag, nat Pd(d,x) 111m,109,101,100 Pd, nat Pd(d,x), 105,102m,102g,101m,101g,100,99m,99g Rh and nat Pd(d,x) 103,97 Ru nuclear reactions by using the stacked foil irradiation technique. The experimental results are compared with our previous results and with the theoretical predictions calculated with the ALICE-D, EMPIRE-D and TALYS (TENDL libraries) codes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Determination of the intrinsic energy dependence of LiF:Mg,Ti thermoluminescent dosimeters for {sup 125}I and {sup 103}Pd brachytherapy sources relative to {sup 60}Co

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

Reed, J. L., E-mail: jlreed2@wisc.edu; Micka, J. A.; Culberson, W. S.

Purpose: To determine the intrinsic energy dependence of LiF:Mg,Ti thermoluminescent dosimeters (TLD-100) for {sup 125}I and {sup 103}Pd brachytherapy sources relative to {sup 60}Co. Methods: LiF:Mg,Ti TLDs were irradiated with low-energy brachytherapy sources and with a {sup 60}Co teletherapy source. The brachytherapy sources measured were the Best 2301 {sup 125}I seed, the OncoSeed 6711 {sup 125}I seed, and the Best 2335 {sup 103}Pd seed. The TLD light output per measured air-kerma strength was determined for the brachytherapy source irradiations, and the TLD light output per air kerma was determined for the {sup 60}Co irradiations. Monte Carlo (MC) simulations were usedmore » to calculate the dose-to-TLD rate per air-kerma strength for the brachytherapy source irradiations and the dose to TLD per air kerma for the {sup 60}Co irradiations. The measured and MC-calculated results for all irradiations were used to determine the TLD intrinsic energy dependence for {sup 125}I and {sup 103}Pd relative to {sup 60}Co. Results: The relative TLD intrinsic energy dependences (relative to {sup 60}Co) and associated uncertainties (k = 1) were determined to be 0.883 ± 1.3%, 0.870 ± 1.4%, and 0.871 ± 1.5% for the Best 2301 seed, OncoSeed 6711 seed, and Best 2335 seed, respectively. Conclusions: The intrinsic energy dependence of TLD-100 is dependent on photon energy, exhibiting changes of 13%–15% for {sup 125}I and {sup 103}Pd sources relative to {sup 60}Co. TLD measurements of absolute dose around {sup 125}I and {sup 103}Pd brachytherapy sources should explicitly account for the relative TLD intrinsic energy dependence in order to improve dosimetric accuracy.« less

Cyclo-oxygenase isozymes in mucosal ulcergenic and functional responses following barrier disruption in rat stomachs.

PubMed

Hirata, T; Ukawa, H; Yamakuni, H; Kato, S; Takeuchi, K

1997-10-01

1. We examined the effects of selective and nonselective cyclo-oxygenase (COX) inhibitors on various functional changes in the rat stomach induced by topical application of taurocholate (TC) and investigated the preferential role of COX isozymes in these responses. 2. Rat stomachs mounted in ex vivo chambers were perfused with 50 mM HCl and transmucosal potential difference (p.d.), mucosal blood flow (GMBF), luminal acid loss and luminal levels of prostaglandin E2 (PGE2) were measured before, during and after exposure to 20 mM TC. 3. Mucosal application of TC in control rats caused a reduction in p.d., followed by an increase of luminal acid loss and GMBF, and produced only minimal damage in the mucosa 2 h later. Pretreatment with indomethacin (10 mg kg[-1], s.c.), a nonselective COX-1 and COX-2 inhibitor, attenuated the gastric hyperaemic response caused by TC without affecting p.d. and acid loss, resulting in haemorrhagic lesions in the mucosa. In contrast, selective COX-2 inhibitors, such as NS-398 and nimesulide (10 mg kg[-1], s.c.), had no effect on any of the responses induced by TC and did not cause gross damage in the mucosa. 4. Luminal PGE2 levels were markedly increased during and after exposure to TC and this response was significantly inhibited by indomethacin but not by either NS-398 or nimesulide. The expression of COX-1-mRNA was consistently detected in the gastric mucosa before and after TC treatment, while a faint expression of COX-2-mRNA was detected only 2 h after TC treatment. 5. Both NS-398 and nimesulide significantly suppressed carrageenan-induced rat paw oedema, similar to indomethacin. 6. These results confirmed a mediator role for prostaglandins in the gastric hyperaemic response following TC-induced barrier disruption, and suggest that COX-1 but not COX-2 is a key enzyme in maintaining 'housekeeping' functions in the gastric mucosa under both normal and adverse conditions.

1-[2-(4-Benzyloxyphenoxy)Ethyl]Imidazole inhibits monoamine oxidase B and protects against neuronal loss and behavioral impairment in rodent models of Parkinson's disease.

PubMed

Chung, Jin Yong; Lee, Ji Won; Ryu, Choon Ho; Min, Hye Kyung; Yoon, Yeo Jin; Lim, Mi Jung; Park, Cheol Hyoung

2015-08-01

Monoamine oxidase B (MAO-B) is well known as a therapeutic target for Parkinson's disease (PD). MAO-B inhibitors retain antiparkinsonism abilities to improve motor function and prevent neuronal loss by decreasing dopamine metabolism and oxidative stress in the brain. From the study to find novel antiparkinsonism drugs that can inhibit MAO-B activity, neuronal loss, and behavioral deficits in the mouse model of PD, we identified that 1-[2-(4-benzyloxyphenoxy)ethyl]imidazole (BPEI) or safinamide strongly and selectively inhibited MAO-B activities in a dose-dependent manner (IC50 of BPEI and safinamide for MAO-B were 0.016 and 0.0021 µM and for MAO-A were 70.0 and 370 µM, respectively). In ex vivo studies after an administration (30 mg/kg, i.p.) of BPEI or safinamide to normal mice, the MAO-B activity in the brain was reduced by up to 90.6% or 82.4% at 1.0 hr. BPEI (20 mg/kg, i.p.) or safinamide (20 mg/kg, i.p.) significantly reversed the behavioral impairments, dopamine levels in the striatum, and neuronal loss in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice compared with the MPTP-alone-treated group. In the 6-hydroxydopamine-induced PD rat model, behavioral improvement by levodopa sparing activity was observed in the BPEI- or safinamide-treated (20 mg/kg, i.p.) rats. Moreover, BPEI revealed additional curative activities for nonmotor symptoms of PD such as pain, anxiety, epilepsy, and depression in rodent disease models. Therefore, BPEI has broad therapeutic potential for treating motor symptoms via strong and selective inhibitory effects on MAO-B, with additional benefits for comorbid symptoms in PD. © 2015 Wiley Periodicals, Inc.

Low Energy Electron Diffraction (LEED)-Auger-Thin-Layer Electrochemical Studies of the Underpotential Deposition of Lead onto Gold Single Crystals.

DTIC Science & Technology

1979-12-15

i’attcns for Clean Au. SinlY \\’ td Fim aroid 107. f-set ting: Q.’ fxposurL INC t ir...12, 1975, pp. 107-124 IFF -169- 103. G. E. Rhead, J. Phys. F:- Metal Phys., 3, L53 (1973). 104. C. S. McKee, M. W. Robaerts and M. L. Williams

33 Years of Peritoneal Dialysis-Associated Peritonitis: A Single-Center Study in Japan.

PubMed

Nakao, Masatsugu; Yamamoto, Izumi; Maruyama, Yukio; Nakashima, Akio; Matsuo, Nanae; Tanno, Yudo; Ohkido, Ichiro; Ikeda, Masato; Yamamoto, Hiroyasu; Yokoyama, Keitaro; Yokoo, Takashi

2016-02-01

Peritoneal dialysis-associated peritonitis (PD-associated peritonitis) could influence the outcome of PD patients, including technique survival. Although the use of the twin-bag system has decreased the incidence of peritonitis, the effects of biocompatible PD solutions are controversial. Additionally, since both infection-causing microorganisms and antimicrobial therapies have changed over time, the duration of treatment of peritonitis (the duration of peritonitis) seems to have changed. The study included 527 patients who received PD between January 1980 and December 2012 at a single center. We divided patients undergoing PD into three groups according to the type of PD system used, namely single-bag and conventional PD solutions (S+C group, N = 145), twin-bag and conventional PD solutions (T+C group, N = 171) and twin-bag and biocompatible PD solutions (T+B group, N = 211), and analyzed PD-associated peritonitis incidences. Incidences of PD-associated peritonitis (times per patient-months) and peritonitis-free time were 1/59.4, 1/70.6 and 1/103.1, and 52, 97, and 100 months for the S+C, T+C and T+B groups, respectively. The duration of peritonitis, has thus, become dramatically shorter in recent years. Streptococcus sp. were associated with shortest and fungi with longest durations of peritonitis. Staphylococcus sp. and Pseudomonas aeruginosa were predominant in the S+C group. The twin-bag system has made a greater contribution to reductions in PD-associated peritonitis than biocompatible PD solutions. Furthermore, changes in microorganisms, antimicrobial therapies, patient education and improved PD system devices have presumably affected the reduction in the duration of peritonitis. © 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Minutes. Accredited Standards Committee on Noise, S12. U.S. Tag for ISO/ TC 43/S1 Noise and ISO/TC 94/SC12 Hearing Protection, Held in Denver, Colorado on 7 October 1993

DTIC Science & Technology

1993-10-07

study at a special session sponsored by the Technical Committee on Noise, on Tuesday afternoon at the Denver, ASA. On Thursday of ASA week (October 7...COMMITTEE ON NOISE. S12 U.S. TAG FOR ISO/TC 43/SCI NOISE and ISO/TC 94/SC1 2 HEARING PP"OTECTION Denver, Colorado 7 October 1993 2As,,,MNUTES 94-03976 )4 2...r AVAIL BRENIG. D. P I, ’,I-pho’e (2? 2428 0373 STANDARDS MANAGER r,4 f’A, (2121 24A0146 S1 2/284 MINUTES OF S12 MEETING HELD IN DENVER, COLORADO, ON

Well-ionization chamber response relative to NIST air-kerma strength standard for prostate brachytherapy seeds.

PubMed

Mitch, M G; Zimmerman, B E; Lamperti, P J; Seltzer, S M; Coursey, B M

2000-10-01

The response of well-ionization chambers to the emissions of 103Pd and 125I radioactive seed sources used in prostate cancer brachytherapy has been measured. Calibration factors relating chamber response (current or dial setting) to measured air-kerma strength have been determined for seeds from nine manufacturers, each with different designs. Variations in well-ionization chamber response relative to measured air-kerma strength have been observed because of differences in the emitted energy spectrum due to both the radionuclide support material (125I seeds) and the mass ratio of 103Pd to 102Pd (103Pd seeds). Obtaining accurate results from quality assurance measurements using well-ionization chambers at a therapy clinic requires knowledge of such differences in chamber response as a function of seed design.

Effect of improved TLD dosimetry on the determination of dose rate constants for {sup 125}I and {sup 103}Pd brachytherapy seeds

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

Rodriguez, M., E-mail: manuel.rodriguez@rmp.uhn.ca; Rogers, D. W. O.

Purpose: To more accurately account for the relative intrinsic energy dependence and relative absorbed-dose energy dependence of TLDs when used to measure dose rate constants (DRCs) for {sup 125}I and {sup 103}Pd brachytherapy seeds, to thereby establish revised “measured values” for all seeds and compare the revised values with Monte Carlo and consensus values. Methods: The relative absorbed-dose energy dependence, f{sup rel}, for TLDs and the phantom correction, P{sub phant}, are calculated for {sup 125}I and {sup 103}Pd seeds using the EGSnrc BrachyDose and DOSXYZnrc codes. The original energy dependence and phantom corrections applied to DRC measurements are replaced bymore » calculated (f{sup rel}){sup −1} and P{sub phant} values for 24 different seed models. By comparing the modified measured DRCs to the MC values, an appropriate relative intrinsic energy dependence, k{sub bq}{sup rel}, is determined. The new P{sub phant} values and relative absorbed-dose sensitivities, S{sub AD}{sup rel}, calculated as the product of (f{sup rel}){sup −1} and (k{sub bq}{sup rel}){sup −1}, are used to individually revise the measured DRCs for comparison with Monte Carlo calculated values and TG-43U1 or TG-43U1S1 consensus values. Results: In general, f{sup rel} is sensitive to the energy spectra and models of the brachytherapy seeds. Values may vary up to 8.4% among {sup 125}I and {sup 103}Pd seed models and common TLD shapes. P{sub phant} values depend primarily on the isotope used. Deduced (k{sub bq}{sup rel}){sup −1} values are 1.074 ± 0.015 and 1.084 ± 0.026 for {sup 125}I and {sup 103}Pd seeds, respectively. For (1 mm){sup 3} chips, this implies an overall absorbed-dose sensitivity relative to {sup 60}Co or 6 MV calibrations of 1.51 ± 1% and 1.47 ± 2% for {sup 125}I and {sup 103}Pd seeds, respectively, as opposed to the widely used value of 1.41. Values of P{sub phant} calculated here have much lower statistical uncertainties than literature values, but systematic uncertainties from density and composition uncertainties are significant. Using these revised values with the literature’s DRC measurements, the average discrepancies between revised measured values and Monte Carlo values are 1.2% and 0.2% for {sup 125}I and {sup 103}Pd seeds, respectively, compared to average discrepancies for the original measured values of 4.8%. On average, the revised measured values are 4.3% and 5.9% lower than the original measured values for {sup 103}Pd and {sup 125}I seeds, respectively. The average of revised DRCs and Monte Carlo values is 3.8% and 2.8% lower for {sup 125}I and {sup 103}Pd seeds, respectively, than the consensus values in TG-43U1 or TG-43U1S1. Conclusions: This work shows that f{sup rel} is TLD shape and seed model dependent suggesting a need to update the generalized energy response dependence, i.e., relative absorbed-dose sensitivity, measured 25 years ago and applied often to DRC measurements of {sup 125}I and {sup 103}Pd brachytherapy seeds. The intrinsic energy dependence for LiF TLDs deduced here is consistent with previous dosimetry studies and emphasizes the need to revise the DRC consensus values reported by TG-43U1 or TG-43U1S1.« less

A comparison of postimplant dosimetry for {sup 103}Pd versus {sup 131}Cs seeds on a retrospective series of PBSI patients

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

Ravi, Ananth; Keller, Brian M.; Pignol, Jean-Philippe

2011-11-15

Purpose: Permanent breast seed implantation (PBSI) is an accelerated partial breast irradiation technique performed using stranded {sup 103}Pd radioactive seeds (average energy of 21 keV, 16.97 day half-life). Since 2004, {sup 131}Cs brachytherapy sources have become clinically available. The {sup 131}Cs radionuclide has a higher energy (average energy of 30 keV) and a shorter half-life (9.7 days) than {sup 103}Pd. The purpose of this study was to determine whether or not there are dosimetric benefits to using {sup 131}Cs brachytherapy seeds for PBSI. Methods: The prescribed dose for PBSI using {sup 103}Pd is 90 Gy, which was adjusted for {supmore » 131}Cs implants to account for the shorter half-life. A retrospective cohort of 30 patients, who have already undergone a {sup 103}Pd implant, was used for this study. The treatments were planned using the Variseed treatment planning system. The air kerma strength of the {sup 131}Cs seeds was adjusted in all preimplantation treatment plans so that the V{sub 100} (the volume within the target that receives 100% or more of the prescribed dose) were equivalent at time of implantation. Two month follow-up CT scans were available for all 30 patients and each patient was reevaluated using {sup 131}Cs seeds. The postimplant dosimetric parameters were compared using a two tailed t-test. Results: The prescribed dose for {sup 131}Cs was calculated to be 77 Gy; this dose would have the same biological effect as a PBSI implant with {sup 103}Pd of 90 Gy. The activities of the {sup 131}Cs sources were adjusted to an average of 2.2 {+-} 0.8 U for {sup 131}Cs compared to 2.5 {+-} 1.1 U for {sup 103}Pd in order to get an equivalent V{sub 100} as the {sup 103}Pd preimplants. While the use of {sup 131}Cs significantly reduces the preimplant V{sub 200} (the volume within the target that receives 200% or more of the prescribed dose) compared to {sup 103}Pd by 13.5 {+-} 9.0%, the reduction observed on the 2 month postimplant plan was 12.4 {+-} 5.1% which accounted for seed motion, implantation inaccuracies and tissue changes. This translates into an absolute reduction of 4.1 cm{sup 3} of tissue receiving 200% of the dose. Conclusions: This analysis of 30 early stage breast cancer patients who underwent the PBSI procedure shows that there is a theoretical dosimetric advantage to using {sup 131}Cs. However, in a realistic implant that will have seed misplacements and tissue changes, the use of {sup 131}Cs may not result in any clinically significant benefit.« less

Nuclear Data Sheets for A = 94

NASA Astrophysics Data System (ADS)

Abriola, D.; Sonzogni, A. A.

2006-09-01

Experimental data on ground- and excited-state properties for all known nuclei with mass number A = 94 have been compiled and evaluated. States populated in radioactive decay, as well as in nuclear reactions, have been considered. For these nuclei, level and decay schemes, as well as tables of nuclear properties, are given. The Hager-Seltzer internal conversion coefficients are listed for gamma rays of known multipolarity. This work supersedes the 1992 evaluation by J.K. Tuli (1992Tu02). Since 1992, many articles have been published which were incorporated in this evaluation. In summary, high-spin data using large arrays of Ge detectors have been obtained for 94Kr (2000Rz02), 94Sr (1995Ha20), 94Zr (2002Fo03,2005Pa48), 94Nb (2000Ma63), 94Mo (1998Kh04), 94Tc (2000Gh01), 94Ru (1994Ju03,1994Ro08), 94Rh (1994Ar33), and 94Pd (2003Ma24). A new isomer was observed in 94Y (1999Ge01). The low-spin levels in 98Mo were systematically studied using a variety of experimental techniques (2003Fr02). Considerable effort was spent investigating the decay of 94Ag and the levels of 94Pd (2006Mu03,2005Mu15,2004BaZY,2004Pl01,2002La18), in particular, the (21+) level in 94Ag is the first level observed to undergo both single and double proton radioactivity.

Effective detection of the tumors causing osteomalacia using [Tc-99m]-HYNIC-octreotide (99mTc-HYNIC-TOC) whole body scan.

PubMed

Jing, Hongli; Li, Fang; Zhuang, Hongming; Wang, Zhenghua; Tian, Jian; Xing, Xiaoping; Jin, Jin; Zhong, Dingrong; Zhang, Jingjing

2013-11-01

Tumor-induced osteomalacia (TIO) is an endocrine disorder caused by tumors producing excessive fibroblast growth factor-23 (FGF-23). The causative tumors are generally small, slow-growing benign mesenchymal tumors. The only cure of the disease depends on resection of the tumors, which are extremely difficult to localize due to their small sizes and rare locations. Since these tumors are known to express somatostatin receptors, this research was undertaken to evaluate efficacy of [Tc-99m]-HYNIC-octreotide (99mTc-HYNIC-TOC) whole body imaging in this clinical setting Images of 99mTc-HYNIC-TOC scans and clinical chart from 183 patients with hypophosphatemia and clinically suspected TIO were retrospectively reviewed. The scan findings were compared to the results of histopathological examinations and clinical follow-ups. Among 183 patients, 72 were confirmed to have TIO while 103 patients were found to have other causes of hypophosphatemia. The possibility of TIO could not be either diagnosed or excluded in the remaining 8 patients. For analytical purposes, these 8 patients who could neither be diagnosed nor excluded as having TIO were regarded as having the disease, bringing the total of TIO patients to 80. The 99mTc-HYNIC-TOC scan identified 69 tumors in 80 patients with TIO, which rendered a sensitivity of 86.3% (69/80). 99mTc-HYNIC-TOC scintigraphy excluded 102 patients without TIO with a specificity of 99.1% (102/103). The overall accuracy of 99mTc-HYNIC-TOC whole body scan in the localization of tumors responsible for osteomalacia is 93.4% (171/183). Whole body 99mTc-HYNIC-TOC imaging is effective in the localization of occult tumors causing TIO. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Dynamic CT for Parathyroid Adenoma Detection: How Does Radiation Dose Compare With Nuclear Medicine?

PubMed

Czarnecki, Caroline A; Einsiedel, Paul F; Phal, Pramit M; Miller, Julie A; Lichtenstein, Meir; Stella, Damien L

2018-05-01

Dynamic CT is increasingly used for preoperative localization of parathyroid adenomas, but concerns remain about the radiation effective dose of CT compared with that of 99m Tc-sestamibi scintigraphy. The purpose of this study was to compare the radiation dose delivered by three-phase dynamic CT with that delivered by 99m Tc-sestamibi SPECT/CT performed in accordance with our current protocols and to assess the possible reduction in effective dose achieved by decreasing the scan length (i.e., z-axis) of two phases of the dynamic CT protocol. The effective dose of a 99m Tc-sestamibi nuclear medicine parathyroid study performed with and without coregistration CT was calculated and compared with the effective dose of our current three-phase dynamic CT protocol as well as a proposed protocol involving CT with reduced scan length. The median effective dose for a 99m Tc-sestamibi nuclear medicine study was 5.6 mSv. This increased to 12.4 mSv with the addition of coregistration CT, which is higher than the median effective dose of 9.3 mSv associated with the dynamic CT protocol. Reducing the scan length of two phases in the dynamic CT protocol could reduce the median effective dose to 6.1 mSv, which would be similar to that of the dose from the 99m Tc-sestamibi study alone. Dynamic CT used for the detection of parathyroid adenoma can deliver a lower radiation dose than 99m Tc-sestamibi SPECT/CT. It may be possible to reduce the dose further by decreasing the scan length of two of the phases, although whether this has an impact on accuracy of the localization needs further investigation.

Is there a valid app for that? Validity of a free pedometer iPhone application.

PubMed

Bergman, Randall J; Spellman, Justin W; Hall, Michael E; Bergman, Shawn M

2012-07-01

This study examined the validity of a selected free pedometer application (iPedometer; IP) for the iPhone that could be used to assess physical activity. Twenty college students (10 men, 10 women; mean age: 21.85 ± 1.57 yrs) wore an iPhone at 3 locations (pocket, waist, arm) and a StepWatch 3 Step Activity Monitor (SW) on their right ankle while walking on a treadmill at 5 different speeds (54, 67, 80, 94, 107 m·min(-1)). A research assistant counted steps with a tally counter (TC). Statistical significance between the TC, SW, and IP was found during every condition except IP in the pocket at 107 m·min(-1) (F(2,38) = .64, P = .54). Correlations involving the IP revealed only 1 positive correlation (IP on arm at 54 m·min(-1)) for any of the conditions (r = .46, P = .05). The IP application was not accurate in counting steps and recorded significantly lower step counts than the SW and TC. Thus, the free pedometer application used is not a valid instrument for monitoring activity during treadmill walking.

A fast and simple dose-calibrator-based quality control test for the radionuclidic purity of cyclotron-produced (99m)Tc.

PubMed

Tanguay, J; Hou, X; Esquinas, P; Vuckovic, M; Buckley, K; Schaffer, P; Bénard, F; Ruth, T J; Celler, A

2015-11-07

Cyclotron production of 99mTc through the (100)Mo(p,2n)99mTc reaction channel is actively being investigated as an alternative to reactor-based (99)Mo generation by nuclear fission of (235)U. Like most radioisotope production methods, cyclotron production of 99mTc will result in creation of unwanted impurities, including Tc and non-Tc isotopes. It is important to measure the amounts of these impurities for release of cyclotron-produced 99mTc (CPTc) for clinical use. Detection of radioactive impurities will rely on measurements of their gamma (γ) emissions. Gamma spectroscopy is not suitable for this purpose because the overwhelming presence of 99mTc and the count-rate limitations of γ spectroscopy systems preclude fast and accurate measurement of small amounts of impurities. In this article we describe a simple and fast method for measuring γ emission rates from radioactive impurities in CPTc. The proposed method is similar to that used to identify (99)Mo breakthrough in generator-produced 99mTc: one dose calibrator (DC) reading of a CPTc source placed in a lead shield is followed by a second reading of the same source in air. Our experimental and theoretical analysis show that the ratio of DC readings in lead to those in air are linearly related to γ emission rates from impurities per MBq of 99mTc over a large range of clinically-relevant production conditions. We show that estimates of the γ emission rates from Tc impurities per MBq of 99mTc can be used to estimate increases in radiation dose (relative to pure 99mTc) to patients injected with CPTc-based radiopharmaceuticals. This enables establishing dosimetry-based clinical-release criteria that can be tested using commercially-available dose calibrators. We show that our approach is highly sensitive to the presence of 93gTc, 93mTc, 94gTc, 94mTc, 95mTc, 95gTc, and 96gTc, in addition to a number of non-Tc impurities.

A fast and simple dose-calibrator-based quality control test for the radionuclidic purity of cyclotron-produced 99mTc

NASA Astrophysics Data System (ADS)

Tanguay, J.; Hou, X.; Esquinas, P.; Vuckovic, M.; Buckley, K.; Schaffer, P.; Bénard, F.; Ruth, T. J.; Celler, A.

2015-11-01

Cyclotron production of {{}99\\text{m}} Tc through the 100Mo(p,2n){{}99\\text{m}} Tc reaction channel is actively being investigated as an alternative to reactor-based 99Mo generation by nuclear fission of 235U. Like most radioisotope production methods, cyclotron production of {{}99\\text{m}} Tc will result in creation of unwanted impurities, including Tc and non-Tc isotopes. It is important to measure the amounts of these impurities for release of cyclotron-produced {{}99\\text{m}} Tc (CPTc) for clinical use. Detection of radioactive impurities will rely on measurements of their gamma (γ) emissions. Gamma spectroscopy is not suitable for this purpose because the overwhelming presence of {{}99\\text{m}} Tc and the count-rate limitations of γ spectroscopy systems preclude fast and accurate measurement of small amounts of impurities. In this article we describe a simple and fast method for measuring γ emission rates from radioactive impurities in CPTc. The proposed method is similar to that used to identify 99Mo breakthrough in generator-produced {{}99\\text{m}} Tc: one dose calibrator (DC) reading of a CPTc source placed in a lead shield is followed by a second reading of the same source in air. Our experimental and theoretical analysis show that the ratio of DC readings in lead to those in air are linearly related to γ emission rates from impurities per MBq of {{}99\\text{m}} Tc over a large range of clinically-relevant production conditions. We show that estimates of the γ emission rates from Tc impurities per MBq of {{}99\\text{m}} Tc can be used to estimate increases in radiation dose (relative to pure {{}99\\text{m}} Tc) to patients injected with CPTc-based radiopharmaceuticals. This enables establishing dosimetry-based clinical-release criteria that can be tested using commercially-available dose calibrators. We show that our approach is highly sensitive to the presence of {{}93\\text{g}} Tc, {{}93\\text{m}} Tc, {{}94\\text{g}} Tc, {{}94\\text{m}} Tc, {{}95\\text{m}} Tc, {{}95\\text{g}} Tc, and {{}96\\text{g}} Tc, in addition to a number of non-Tc impurities.

Complication Rates among Trauma Centers

PubMed Central

Ang, Darwin N; Rivara, Frederick P; Nathens, Avery; Jurkovich, Gregory J; Maier, Ronald V; Wang, Jin; MacKenzie, Ellen J

2009-01-01

Background To examine the association between patient complications and admission to level 1 trauma centers (TC) compared to non-trauma centers (NTC). Study Design A retrospective cohort study of data derived from the National Study on the Costs and Outcomes of Trauma (NSCOT). Patients were recruited from 18 level 1 TC and 51 NTC in 15 regions encompassing 14 states. Trained study nurses, using standardized forms, abstracted the medical records of the patients. The overall number of complications per patient was identified as well as the presence or absence of 13 specific complications. Results Patients treated in TC were more likely to have any complication compared to NTC with an adjusted relative risk (RR) of 1.34 (95% CI 1.03, 1.74). For individual complications, only urinary tract infection RR 1.94 (95% CI 1.07, 3.17) was significantly higher in TC. TC patients were more likely to have three or more complications, RR 1.83 (95% CI 1.16, 2.90). Treatment variables that are surrogates for markers of injury severity, such as use of pulmonary artery catheters, multiple operations, massive transfusions (> 2,500mL packed red blood cells), and invasive brain catheters, occurred significantly more often in TC. Conclusions Trauma centers have a slightly higher incidence rate of complications even after adjusting for patient case mix. Aggressive treatment may account for a significant portion of TC-associated complications. PA catheter use and intubation had the most influence on overall TC complication rates. Further study is needed to provide accurate benchmark measures of complication rates and to determine their causes. PMID:19854399

Dye-induced aggregation of single stranded RNA: a mechanistic approach.

PubMed

Biver, Tarita; Ciatto, Carlo; Secco, Fernando; Venturini, Marcella

2006-08-15

The binding of proflavine (D) to single stranded poly(A) (P) was investigated at pH 7.0 and 25 degrees C using T-jump, stopped-flow and spectrophotometric methods. Equilibrium measurements show that an external complex PD(I) and an internal complex PD(II) form upon reaction between P and D and that their concentrations depend on the polymer/dye concentration ratio (C(P)/C(D)). For C(P)/C(D)<2.5, cooperative formation of stacks external to polymer strands prevails (PD(I)). Equilibria and T-jump experiments, performed at I=0.1M and analyzed according to the Schwarz theory for cooperative binding, provide the values of site size (g=1), equilibrium constant for the nucleation step (K( *)=(1.4+/-0.6)x10(3)M(-1)), equilibrium constant for the growth step (K=(1.2+/-0.6)x10(5)M(-1)), cooperativity parameter (q=85) and rate constants for the growth step (k(r)=1.2x10(7)M(-1)s(-1), k(d)=1.1 x 10(2)s(-1)). Stopped-flow experiments, performed at low ionic strength (I=0.01 M), indicate that aggregation of stacked poly(A) strands do occur provided that C(P)/C(D)<2.5.

PO2 modulation of paraquat-induced microvascular injury in isolated dog lungs.

PubMed

Shibamoto, T; Taylor, A E; Parker, J C

1990-05-01

We determined the effects of paraquat (PQ) concentrations ranging from 10(-3) to 10(-2) M and three levels of venous PO2 [hypoxia (41 +/- 3 Torr), normoxia (147 +/- 8 Torr), and hyperoxia (444 +/- 17 Torr)] in the presence of 4 x 10(-3) M PQ on microvascular permeability in isolated blood-perfused dog lungs. Capillary filtration coefficient (Kf,c) increased and isogravimetric capillary pressure (Pc,i) decreased 3 h after perfusion with 10(-2) M PQ (n = 7) and 5 h after perfusion with 4 x 10(-3) M PQ (n = 6) but not with 10(-3) M PQ (n = 4). In hyperoxic lungs perfused with 4 x 10(-3) M PQ, Kf,c increased to nine times the base-line value 5 h after PQ [0.15 +/- 0.01 to 1.35 +/- 0.25 (SE) ml.min-1.cmH2O-1.100 g-1]. Pc,i significantly decreased from a base-line value of 9.4 +/- 0.2 to 7.1 +/- 0.4 cmH2O at 3 h. In hypoxic lungs perfused with 4 x 10(-3) M PQ (n = 5), Pc,i and Kf,c changes were not significantly different from those in normoxic lungs treated with PQ. Thus both hyperoxia and an increased dose of PQ shortened the latent period and increased the severity of the PQ-induced microvascular permeability lesion, but hypoxia failed to prevent the PQ damage.

Gold nanoparticle-aided brachytherapy with vascular dose painting: estimation of dose enhancement to the tumor endothelial cell nucleus.

PubMed

Ngwa, Wilfred; Makrigiorgos, G Mike; Berbeco, Ross I

2012-01-01

Theoretical microdosimetry at the subcellular level is employed in this study to estimate the dose enhancement to tumor endothelial cell nuclei, caused by radiation-induced photo/Auger electrons originating from gold nanoparticles (AuNPs) targeting the tumor endothelium, during brachytherapy. A tumor vascular endothelial cell (EC) is modeled as a slab of 2 μm (thickness) × 10 μm (length) × 10 μm (width). The EC contains a nucleus of 5 μm diameter and thickness of 0.5-1 μm, corresponding to nucleus size 5%-10% of cellular volume, respectively. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the dose enhancement to the nucleus caused by photo/Auger electrons from AuNPs attached to the exterior surface of the EC. The nucleus dose enhancement factor (nDEF), representing the ratio of the dose to the nucleus with and without the presence of gold nanoparticles was calculated for different AuNP local concentrations. The investigated concentration range considers the potential for significantly higher local concentration near the EC due to preferential accumulation of AuNP in the tumor vasculature. Four brachytherapy sources: I-125, Pd-103, Yb-169, and 50 kVp x-rays were investigated. For nucleus size of 10% of the cellular volume and AuNP concentrations ranging from 7 to 140 mg/g, brachytherapy sources Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 5.6-73, 4.8-58.3, 4.7-56.6, and 3.2-25.8, respectively. Meanwhile, for nucleus size 5% of the cellular volume in the same concentration range, Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 6.9-79.2, 5.1-63.2, 5.0-61.5, and 3.3-28.3, respectively. The results predict that a substantial dose boost to the nucleus of endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs in combination with brachytherapy. Such vascular dose boosts could induce tumor vascular shutdown, prompting extensive tumor cell death.

Possible association of 3' UTR +357 A>G, IVS11-nt 93 T>C, c.1311 C>T polymorphism with G6PD deficiency.

PubMed

Sirdah, Mahmoud M; Shubair, Mohammad E; Al-Kahlout, Mustafa S; Al-Tayeb, Jamal M; Prchal, Josef T; Reading, N Scott

2017-07-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked inherited enzymopathic disorder affecting more than 500 million people worldwide. It has so far been linked to 217 distinct genetic variants in the exons and exon-intron boundaries of the G6PD gene, giving rise to a wide range of biochemical heterogeneity and clinical manifestations. Reports from different settings suggested the association of intronic and other mutations outside the reading frame of the G6PD gene with reduced enzyme activity and presenting clinical symptoms. The present study aimed to investigate any association of other variations apart of the exonic or exonic intronic boundaries in the development of G6PD deficiency. Sixty-seven unrelated Palestinian children admitted to the pediatric hospital with hemolytic crises due to G6PD deficiency were studied. In our Palestinian cohort of 67 [59 males (M) and 8 females (F)] G6PD-deficient children, previously hospitalized for acute hemolytic anemia due to favism, molecular sequencing of the G6PD gene revealed four cases (3M and 1F) that did not have any of the variants known to cause G6PD deficiency, but the 3' UTR c.*+357A>G (rs1050757) polymorphism in association with IVS 11 (c.1365-13T>C; rs2071429), and c.1311C>T (rs2230037). We now provide an additional evidence form Palestinian G6PD-deficient subjects for a possible role of 3' UTR c.*+357 A>G, c.1365-13T>C, and/or c.1311C>T polymorphism for G6PD deficiency, suggesting that not only a single variation in the exonic or exonic intronic boundaries, but also a haplotype of G6PD should considered as a cause for G6PD deficiency.

Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 3: optimization of [1,2,4]triazolo[1,5-a]pyrimidine core via structure-based and physicochemical property-driven approaches.

PubMed

Huang, Boshi; Li, Cuicui; Chen, Wenmin; Liu, Tao; Yu, Mingyan; Fu, Lu; Sun, Yueyue; Liu, Huiqing; De Clercq, Erik; Pannecouque, Christophe; Balzarini, Jan; Zhan, Peng; Liu, Xinyong

2015-03-06

In our arduous efforts to develop new potent HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs), novel piperidine-linked [1,2,4]triazolo[1,5-a]pyrimidine derivatives were designed, synthesized and evaluated for their antiviral activities in MT-4 cell cultures. Biological results showed that all of the title compounds displayed moderate to excellent activities against wild-type (wt) HIV-1 strain (IIIB) with EC50 values ranging from 8.1 nM to 2284 nM in a cell-based assay. Among them, the most promising analog 7d possessed an EC50 value of 8.1 nM against wt HIV-1, which was much more potent than the reference drugs DDI, 3 TC, NVP and DLV. Additionally, 7d demonstrated weak activity against the double mutant HIV-1 strain (K103N + Y181C), and was more efficient than NVP in a RT inhibition assay. Besides, some measured and calculated physicochemical properties of 7d, like log P and water solubility, as well as the structure-activity relationships (SARs) analysis have been discussed in detail. Furthermore, the binding mode of the active compound 7d was rationalized by molecular simulation studies. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Microsoft Kinect can distinguish differences in over-ground gait between older persons with and without Parkinson's disease.

PubMed

Eltoukhy, Moataz; Kuenze, Christopher; Oh, Jeonghoon; Jacopetti, Marco; Wooten, Savannah; Signorile, Joseph

2017-06-01

Gait patterns differ between healthy elders and those with Parkinson's disease (PD). A simple, low-cost clinical tool that can evaluate kinematic differences between these populations would be invaluable diagnostically; since gait analysis in a clinical setting is impractical due to cost and technical expertise. This study investigated the between group differences between the Kinect and a 3D movement analysis system (BTS) and reported validity and reliability of the Kinect v2 sensor for gait analysis. Nineteen subjects participated, eleven without (C) and eight with PD (PD). Outcome measures included spatiotemporal parameters and kinematics. Ankle range of motion for C was significantly less during ankle swing compared to PD (p=0.04) for the Kinect. Both systems showed significant differences for stride length (BTS (C 1.24±0.16, PD=1.01±0.17, p=0.009), Kinect (C=1.24±0.17, PD=1.00±0.18, p=0.009)), gait velocity (BTS (C=1.06±0.14, PD=0.83±0.15, p=0.01), Kinect (C=1.06±0.15, PD=0.83±0.16, p=0.01)), and swing velocity (BTS (C=2.50±0.27, PD=2.12±0.36, p=0.02), Kinect (C=2.32±0.25, PD=1.95±0.31, p=0.01)) between groups. Agreement (Range ICC =0.93-0.99) and consistency (Range ICC =0.94-0.99) were excellent between systems for stride length, stance duration, swing duration, gait velocity, and swing velocity. The Kinect v2 can was sensitive enough to detect between group differences and consistently produced results similar to the BTS system. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Comparison of 99mTc-UBI 29-41, 99mTc-Ciprofloxacin, 99mTc-Ciprofloxacin dithiocarbamate and 111In-biotin for targeting experimental Staphylococcus aureus and Escherichia coli foreign-body infections: an ex-vivo study.

PubMed

Auletta, Sveva; Baldoni, Daniela; Varani, Michela; Galli, Filippo; Hajar, Iman A; Duatti, Adriano; Ferro-Flores, Guillermina; Trampuz, Andrej; Signore, Alberto

2017-08-28

Diagnosis of implant-associated infection is challenging. Several radiopharmaceuticals have been described but direct comparisons are limited. Here we compared in vitro and in an animal model 99mTc-UBI, 99mTc-Ciprofloxacin, 99mTcN-CiproCS2 and 111In-DTPA-biotin for targeting E. coli (ATCC 25922) and S. aureus (ATCC 43335). Stability controls were performed with the labelled radiopharmaceuticals during 6 h in saline and serum. The in vitro binding to viable or killed bacteria was evaluated at 37 °C and 4 °C. For in vivo studies, Teflon cages were subcutaneously implanted in mice, followed by percutaneous infection. Biodistribution of i.v. injected radiolabelled radiopharmaceuticals were evaluated during 24 h in cages and dissected tissues. Labelling efficiency of all radiopharmaceuticals ranged between 94% and 98%, with high stability both in saline and in human serum. In vitro binding assays displayed a rapid but poor bacterial binding for all tested agents. Similar binding kinetic occurred also with heat-killed and ethanol-killed bacteria. In the tissue cage model, infection was detected at different time points: 99mTc-UBI and 99mTcN-CiproCS2 showed higher infected cage/sterile cage ratio at 24 h for both E. coli and S. aureus; 99mTc-Ciprofloxacin at 24 h for both E. coli and at 4 h for S. aureus; 111In-DTPA-biotin accumulates faster in both E. coli and S. aureus infected cages. 99mTc-UBI, 99mTcN-CiproCS2 showed poor in vitro binding but good in vivo binding to E. coli only. 111In-DTPA-biotin showed poor in vitro binding but good in vivo binding to S. aureus and poor to E. coli. 99mTc-Ciprofloxacin showed poor in vitro binding but good in vivo binding to all tested bacteria. The mechanism of accumulation in infected sites remains to be elucidated.

A cross-country comparison of tobacco consumption among youths from selected South-Asian countries

PubMed Central

2013-01-01

Background Tobacco consumption (TC) among youths poses significant public health problem in developing countries. This study utilized the data of Global Youth Tobacco Survey (GYTS), 2007 to examine and compare youth TC behavior in Bangladesh, Nepal and Sri Lanka. Methods The GYTS covered a total of 2,242 Bangladeshi, 1,444 Nepalese and 1,377 Sri-Lankan youths aged 13–15 years. They represented response rates of 88.9%, 94.6%, and 85.0% for the three countries, respectively. Socioeconomic, environmental, motivating, and programmatic predictors of TC were examined using cross tabulations and logistic regressions. Results Prevalence of TC was 6.9% (9.1% in males, 5.1% in females) in Bangladesh, 9.4% (13.2% in males, 5.3% in females) in Nepal and 9.1% (12.4% in males, 5.8% in females) in Sri Lanka. The average tobacco initiation age was 9.6, 10.24 and 8.61 years, respectively. Cross tabulations showed that gender, smoking among parents and friends, exposure to smoking at home and public places, availability of free tobacco were significantly (P < 0.001) associated with TC in all three countries. The multivariable analysis [odds ratio (95% confidence interval)] indicated that the common significant predictors for TC in the three countries were TC among friends [1.9 (1.30-2.89) for Bangladesh, 4.10 (2.64-6.38) for Nepal, 2.34 (1.36-4.02) for Sri Lanka], exposure to smoking at home [1.7 (1.02-2.81) for Bangladesh, 1.81 (1.08-2.79) for Nepal, 3.96 (1.82-8.62) for Sri Lanka], exposure to smoking at other places [2.67 (1.59-4.47) for Bangladesh, 5.22 (2.76-9.85) for Nepal, 1.76 (1.05-2.88) for Sri Lanka], and the teaching of smoking hazards in schools [0.56 (0.38-0.84) for Bangladesh, 0.60 (0.41-0.89) for Nepal, 0.58 (0.35-0.94) for Sri Lanka]. Conclusions An understanding of the influencing factors of youth TC provides helpful insights for the formulation of tobacco control policies in the South-Asian region. PMID:23617464

Pressure Dependence Transport Studies of the Possible Charge Kondo Effect in Tl-doped PbTe

NASA Astrophysics Data System (ADS)

Kurosaki, Yosuke; Shinagawa, Jun; Matsushita, Yana; Geballe, Ted; Fisher, Ian; Brown, Stuart

2006-03-01

Pb1-xTlxTe is noteworthy for a high superconducting transition temperature relative to carrier concentration, as well as normal state properties consistent with a charge-Kondo effect. Recent experiments also demonstrate that the onset of an observable superconducting Tc with Tl concentration at x˜0.3% coincides with features characteristic of charge Kondo [1], including dρ/dT<0 at low temperatures and an unusual linear variation of the resistivity ρ(T)=ρ0+AT at higher temperatures. Together, these observations are consistent with an association between the two phenomena [2]. We report the effect of applied pressures up to P˜1.5GPa on ρ(T), Tc, and the Hall number pH≡RH-1 for x= 0.3%, 0.8%, and 1.3%. Tc is reduced sharply with pressure, dTc/dP=400-500mK/GPa as the low temperature Kondo- like upturn in ρ(T) is weakened. Also, dA/dP<0 and dpH/dP>0. These observations are discussed in the context of the proposed charge-Kondo model for Pb1-xTlxTe. [1] Y. Matsushita, H. Bluhm, T.H. Geballe and I.R. Fisher, Phys.Rev.Lett. 94, 157002(2005).[2] M. Dzero and J. Schmalian, Phys.Rev.Lett. 94, 157003 (2005). This work is supported by NSF frant DMR-0520552.

Defining the pathogenesis of the human Atp12p W94R mutation using a Saccharomyces cerevisiae yeast model.

PubMed

Meulemans, Ann; Seneca, Sara; Pribyl, Thomas; Smet, Joel; Alderweirldt, Valerie; Waeytens, Anouk; Lissens, Willy; Van Coster, Rudy; De Meirleir, Linda; di Rago, Jean-Paul; Gatti, Domenico L; Ackerman, Sharon H

2010-02-05

Studies in yeast have shown that a deficiency in Atp12p prevents assembly of the extrinsic domain (F(1)) of complex V and renders cells unable to make ATP through oxidative phosphorylation. De Meirleir et al. (De Meirleir, L., Seneca, S., Lissens, W., De Clercq, I., Eyskens, F., Gerlo, E., Smet, J., and Van Coster, R. (2004) J. Med. Genet. 41, 120-124) have reported that a homozygous missense mutation in the gene for human Atp12p (HuAtp12p), which replaces Trp-94 with Arg, was linked to the death of a 14-month-old patient. We have investigated the impact of the pathogenic W94R mutation on Atp12p structure/function. Plasmid-borne wild type human Atp12p rescues the respiratory defect of a yeast ATP12 deletion mutant (Deltaatp12). The W94R mutation alters the protein at the most highly conserved position in the Pfam sequence and renders HuAtp12p insoluble in the background of Deltaatp12. In contrast, the yeast protein harboring the corresponding mutation, ScAtp12p(W103R), is soluble in the background of Deltaatp12 but not in the background of Deltaatp12Deltafmc1, a strain that also lacks Fmc1p. Fmc1p is a yeast mitochondrial protein not found in higher eukaryotes. Tryptophan 94 (human) or 103 (yeast) is located in a positively charged region of Atp12p, and hence its mutation to arginine does not alter significantly the electrostatic properties of the protein. Instead, we provide evidence that the primary effect of the substitution is on the dynamic properties of Atp12p.

Checkpoint inhibitors in triple-negative breast cancer (TNBC): Where to go from here.

PubMed

Kwa, Maryann J; Adams, Sylvia

2018-05-15

Advances in cancer immunotherapy and a growing body of research have focused on the role of the antitumor response in breast cancer. Triple-negative breast cancer (TNBC) is the most immunogenic breast cancer subtype, and there is strong evidence that tumor-infiltrating lymphocytes in TNBC have prognostic value and are associated with clinical outcome and improved survival. Evading antitumor immunity is a hallmark for the development and progression of cancer. Immunotherapy studies have focused on the role of the programmed cell death-1 (PD-1) receptor/programmed death-ligand 1 (PD-L1) pathway in maintaining immunosuppression in the tumor microenvironment. Blockade of the PD-1/PD-L1 axis has emerged as a promising therapeutic option to enhance antitumor immunity and is actively being investigated in TNBC, with encouraging results. In this article, the authors review the current literature on checkpoint inhibitors in TNBC with a focus on PD-1/PD-L1 antibodies and discuss combination strategies and novel approaches for improving antitumor immunity and clinical outcome. Cancer 2018;124:2086-103. © 2018 American Cancer Society. © 2018 American Cancer Society.

Hippocampal perfusion predicts impending neurodegeneration in REM sleep behavior disorder.

PubMed

Dang-Vu, Thien Thanh; Gagnon, Jean-François; Vendette, Mélanie; Soucy, Jean-Paul; Postuma, Ronald B; Montplaisir, Jacques

2012-12-11

Patients with idiopathic REM sleep behavior disorder (IRBD) are at risk for developing Parkinson disease (PD) and dementia with Lewy bodies (DLB). We aimed to identify functional brain imaging patterns predicting the emergence of PD and DLB in patients with IRBD, using SPECT with (99m)Tc-ethylene cysteinate dimer (ECD). Twenty patients with IRBD were scanned at baseline during wakefulness using (99m)Tc-ECD SPECT. After a follow-up of 3 years on average, patients were divided into 2 groups according to whether or not they developed defined neurodegenerative disease (PD, DLB). SPECT data analysis comparing regional cerebral blood flow (rCBF) between groups assessed whether specific brain perfusion patterns were associated with subsequent clinical evolution. Regression analysis between rCBF and clinical markers of neurodegeneration (motor, color vision, olfaction) looked for neural structures involved in this process. Of the 20 patients with IRBD recruited for this study, 10 converted to PD or DLB during the follow-up. rCBF at baseline was increased in the hippocampus of patients who would later convert compared with those who would not (p < 0.05 corrected). Hippocampal perfusion was correlated with motor and color vision scores across all IRBD patients. (99m)Tc-ECD SPECT identifies patients with IRBD at risk for conversion to other neurodegenerative disorders such as PD or DLB; disease progression in IRBD is predicted by abnormal perfusion in the hippocampus at baseline. Perfusion within this structure is correlated with clinical markers of neurodegeneration, further suggesting its involvement in the development of presumed synucleinopathies.

Simultaneous acquisition of (99m)Tc- and (123)I-labeled radiotracers using a preclinical SPECT scanner with CZT detectors.

PubMed

Kobayashi, Masato; Matsunari, Ichiro; Nishi, Kodai; Mizutani, Asuka; Miyazaki, Yoshiharu; Ogai, Kazuhiro; Sugama, Jyunko; Shiba, Kazuhiro; Kawai, Keiichi; Kinuya, Seigo

2016-05-01

Simultaneous acquisition of (99m)Tc and (123)I was evaluated using a preclinical SPECT scanner with cadmium zinc telluride (CZT)-based detectors. 10-ml cylindrical syringes contained about 37 MBq (99m)Tc-tetrofosmin ((99m)Tc-TF) or 37 MBq (123)I-15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid ((123)I-BMIPP) were used to assess the relationship between these SPECT radioactive counts and radioactivity. Two 10-ml syringes contained 100 or 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP to assess the influence of (99m)Tc upscatter and (123)I downscatter, respectively. A rat-sized cylindrical phantom also contained both 100 or 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP. The two 10-ml syringes and phantom were scanned using a pinhole collimator for rats. Myocardial infarction model rats were examined using 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP. Two 1-ml syringes contained 105 MBq (99m)Tc-labeled hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) and 35 MBq (123)I-labeled N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ((123)I-FP-CIT). The two 1-ml syringes were scanned using a pinhole collimator for mice. Normal mice were examined using 105 MBq (99m)Tc-HMPAO and 35 MBq (123)I-FP-CIT. The relationship between SPECT radioactive counts and radioactivity was excellent. Downscatter contamination of (123)I-BMIPP exhibited fewer radioactive counts for 300 MBq (99m)Tc-TF without scatter correction (SC) in 125-150 keV. There was no upscatter contamination of (99m)Tc-TF in 150-175 keV. In the rat-sized phantom, the radioactive count ratio decreased to 4.0 % for 300 MBq (99m)Tc-TF without SC in 125-150 keV. In the rats, myocardial images and radioactive counts of (99m)Tc-TF with the dual tracer were identical to those of the (99m)Tc-TF single injection. Downscatter contamination of (123)I-FP-CIT was 4.2 % without SC in 125-150 keV. In the first injection of (99m)Tc-HMPAO and second injection of (123)I-FP-CIT, brain images and radioactive counts of (99m)Tc-HMPAO with the dual tracer in normal mice also were the similar to those of the (99m)Tc-HMPAO single injection. In the first injection of (123)I-FP-CIT and second injection of (99m)Tc-HMPAO, the brain images and radioactive counts with the dual tracer were not much different from those of the (123)I-FP-CIT single injection. Dual-tracer imaging of (99m)Tc- and (123)I-labeled radiotracers is feasible in a preclinical SPECT scanner with CZT detector. When higher radioactivity of (99m)Tc-labeled radiotracers relative to (123)I-labeled radiotracers is applied, correction methods are not necessarily required for the quantification of (99m)Tc- and (123)I-labeled radiotracers when using a preclinical SPECT scanner with CZT detector.

The impact of alternative pricing methods for drugs in California Workers’ Compensation System: Fee-schedule pricing

PubMed Central

Wilson, Leslie; Turkistani, Fatema A.; Huang, Wei; Tran, Dang M.; Lin, Tracy Kuo

2018-01-01

Introduction California’s Workers’ Compensation System (CAWCS) Department of Industrial Relations questioned the adequacy of the current Medi-Cal fee-schedule pricing and requested analysis of alternatives that maximize price availability and maintain budget neutrality. Objectives To compare CAWCS pharmacy-dispensed (PD) drug prices under alternative fee schedules, and identify combinations of alternative benchmarks that have prices available for the largest percentage of PD drugs and that best reach budget neutrality. Methods Claims transaction-level data (2011–2013) from CAWCS were used to estimate total annual PD pharmaceutical payments. Medi-Cal pricing data was from the Workman’s Compensation Insurance System (WCIS). Average Wholesale Prices (AWP), Wholesale Acquisition Costs (WAC), Direct Prices (DP), Federal Upper Limit (FUL) prices, and National Average Drug Acquisition Costs (NADAC) were from Medi-Span. We matched National Drug Codes (NDCs), pricing dates, and drug quantity for comparisons. We report pharmacy-dispensed (PD) claims frequency, reimbursement matching rate, and paid costs by CAWCS as the reference price against all alternative price benchmarks. Results Of 12,529,977 CAWCS claims for pharmaceutical products 11.6% (1,462,814) were for PD drugs. Prescription drug cost for CAWCS was over $152M; $63.9M, $47.9M, and $40.6M in 2011–2013. Ninety seven percent of these CAWCS PD claims had a Medi-Cal price. Alternative mechanisms provided a price for fewer claims; NADAC 94.23%, AWP 90.94%, FUL 73.11%, WAC 66.98%, and DP 14.33%. Among CAWCS drugs with no Medi-Cal price in PD claims, AWP, WAC, NADAC, DP, and FUL provided prices for 96.7%, 63.14%, 24.82%, 20.83%, and 15.08% of claims. Overall CAWCS paid 100.52% of Medi-Cal, 60% of AWP, 97% of WAC, 309.53% of FUL, 103.83% of DP, and 136.27% of NADAC. Conclusions CAWCS current Medi-Cal fee-schedule price list for PD drugs is more complete than all alternative fee-schedules. However, all reimbursement approaches would require combinations of pricing benchmarks. We suggest keeping primary reimbursement at 100% of Medi-Cal and for drugs without a primary Medi-Cal price calculating the maximum fee as 60% of AWP and then 97% of WAC. Alternatively, we suggest using NADAC as a primary fee-schedule followed by either 60% AWP and 97% WAC or AWP-40% for drugs with no NADAC price. Fee-schedules may not offer the best price and a formulary approach may provide more flexibility. PMID:29799850

The impact of alternative pricing methods for drugs in California Workers' Compensation System: Fee-schedule pricing.

PubMed

Wilson, Leslie; Turkistani, Fatema A; Huang, Wei; Tran, Dang M; Lin, Tracy Kuo

2018-01-01

California's Workers' Compensation System (CAWCS) Department of Industrial Relations questioned the adequacy of the current Medi-Cal fee-schedule pricing and requested analysis of alternatives that maximize price availability and maintain budget neutrality. To compare CAWCS pharmacy-dispensed (PD) drug prices under alternative fee schedules, and identify combinations of alternative benchmarks that have prices available for the largest percentage of PD drugs and that best reach budget neutrality. Claims transaction-level data (2011-2013) from CAWCS were used to estimate total annual PD pharmaceutical payments. Medi-Cal pricing data was from the Workman's Compensation Insurance System (WCIS). Average Wholesale Prices (AWP), Wholesale Acquisition Costs (WAC), Direct Prices (DP), Federal Upper Limit (FUL) prices, and National Average Drug Acquisition Costs (NADAC) were from Medi-Span. We matched National Drug Codes (NDCs), pricing dates, and drug quantity for comparisons. We report pharmacy-dispensed (PD) claims frequency, reimbursement matching rate, and paid costs by CAWCS as the reference price against all alternative price benchmarks. Of 12,529,977 CAWCS claims for pharmaceutical products 11.6% (1,462,814) were for PD drugs. Prescription drug cost for CAWCS was over $152M; $63.9M, $47.9M, and $40.6M in 2011-2013. Ninety seven percent of these CAWCS PD claims had a Medi-Cal price. Alternative mechanisms provided a price for fewer claims; NADAC 94.23%, AWP 90.94%, FUL 73.11%, WAC 66.98%, and DP 14.33%. Among CAWCS drugs with no Medi-Cal price in PD claims, AWP, WAC, NADAC, DP, and FUL provided prices for 96.7%, 63.14%, 24.82%, 20.83%, and 15.08% of claims. Overall CAWCS paid 100.52% of Medi-Cal, 60% of AWP, 97% of WAC, 309.53% of FUL, 103.83% of DP, and 136.27% of NADAC. CAWCS current Medi-Cal fee-schedule price list for PD drugs is more complete than all alternative fee-schedules. However, all reimbursement approaches would require combinations of pricing benchmarks. We suggest keeping primary reimbursement at 100% of Medi-Cal and for drugs without a primary Medi-Cal price calculating the maximum fee as 60% of AWP and then 97% of WAC. Alternatively, we suggest using NADAC as a primary fee-schedule followed by either 60% AWP and 97% WAC or AWP-40% for drugs with no NADAC price. Fee-schedules may not offer the best price and a formulary approach may provide more flexibility.

[Assessment of myocardial perfusion and left ventricular function with 99mTc-PPN 1011].

PubMed

Kumita, S; Mizumura, S; Oishi, T; Kumazaki, T; Sano, J; Yamazaki, Y; Munakata, K

1993-04-01

First-pass radionuclide angiography (FPRNA) was performed with the new myocardial perfusion agent 99mTc-1,2,bis[bis(2-ethoxyethyl)phosphino] ethane (99mTc-PPN 1011) on stress and at rest. One hour after that, myocardial perfusion was counted by 99mTc-PPN 1011 SPECT. Left ventricular ejection fraction (LVEF) obtained by FPRNA correlated with that by multigated image with 99mTc-HSAD (r = 0.94, n = 11). The reduction of left ventricular function under the exercise (delta LVEF) and the increase of severity score (delta Severity score) have a good relation (r = 0.88) in 7 patients with prior myocardial infarction. Thus 99mTc-PPN 1011 appears to be an ideal radiopharmaceutical for evaluation of ventricular function and myocardial perfusion.

Nuclear Data Sheets for A = 94

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

Abriola, D.; Sonzogni, A.A.

Experimental data on ground- and excited-state properties for all known nuclei with mass number A = 94 have been compiled and evaluated. States populated in radioactive decay, as well as in nuclear reactions, have been considered. For these nuclei, level and decay schemes, as well as tables of nuclear properties, are given. The Hager-Seltzer internal conversion coefficients are listed for gamma rays of known multipolarity. This work supersedes the 1992 evaluation by J.K. Tuli (1992Tu02). Since 1992, many articles have been published which were incorporated in this evaluation. In summary, high-spin data using large arrays of Ge detectors have beenmore » obtained for {sup 94}Kr (2000Rz02), {sup 94}Sr (1995Ha20), {sup 94}Zr (2002Fo03,2005Pa48), {sup 94}Nb (2000Ma63), {sup 94}Mo (1998Kh04), {sup 94}Tc (2000Gh01), {sup 94}Ru (1994Ju03,1994Ro08), {sup 94}Rh (1994Ar33), and {sup 94}Pd (2003Ma24). A new isomer was observed in {sup 91}999Ge01). The low-spin levels in {sup 98}Mo were systematically studied using a variety of experimental techniques (2003Fr02). Considerable effort was spent investigating the decay of {sup 94}Ag and the levels of {sup 94}Pd (2006Mu03,2005Mu15,2004BaZY,2004Pl01,2002La18), in particular, the (21+) level in {sup 94}Ag is the first level observed to undergo both single and double proton radioactivity.« less

Comparison of Intraoperatively Built Custom Linked Seeds Versus Loose Seed Gun Applicator Technique Using Real-Time Intraoperative Planning for Permanent Prostate Brachytherapy

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

Zauls, A. Jason; Ashenafi, Michael S.; Onicescu, Georgiana

2011-11-15

Purpose: To report our dosimetric results using a novel push-button seed delivery system that constructs custom links of seeds intraoperatively. Methods and Materials: From 2005 to 2007, 43 patients underwent implantation using a gun applicator (GA), and from 2007 to 2008, 48 patientsunderwent implantation with a novel technique allowing creation of intraoperatively built custom links of seeds (IBCL). Specific endpoint analyses were prostate D90% (pD90%), rV100% > 1.3 cc, and overall time under anesthesia. Results: Final analyses included 91 patients, 43 GA and 48 IBCL. Absolute change in pD90% ({Delta}pD90%) between intraoperative and postoperative plans was evaluated. Using GA method,more » the {Delta}pD90% was -8.1Gy and -12.8Gy for I-125 and Pd-103 implants, respectively. Similarly, the IBCL technique resulted in a {Delta}pD90% of -8.7Gy and -9.8Gy for I-125 and Pd-103 implants, respectively. No statistically significant difference in {Delta}pD90% was found comparing methods. The GA method had two intraoperative and 10 postoperative rV100% >1.3 cc. For IBCL, five intraoperative and eight postoperative plans had rV100% >1.3 cc. For GA, the mean time under anesthesia was 75 min and 87 min for Pd-103 and I-125 implants, respectively. For IBCL, the mean time was 86 and 98 min for Pd-103 and I-125. There was a statistical difference between the methods when comparing mean time under anesthesia. Conclusions: Dosimetrically relevant endpoints were equivalent between the two methods. Currently, time under anesthesia is longer using the IBCL technique but has decreased over time. IBCL is a straightforward brachytherapy technique that can be implemented into clinical practice as an alternative to gun applicators.« less

Defense Authorization and Appropriations Bills: FY1970-FY2016

DTIC Science & Technology

2016-04-20

103-335 9/30/94 1996 H.R. 2126 104-208 7/27/95 9/7/95 # 646 (y294-n125) 104-261 9/29/95 # 700 (y151-n267) S. 1087 104-124 7/28/95 Hh...1990, and passed H.R. 5803 in lieu. h. Senate passed S. 1087 , amended by recorded vote # 397 on September 5, 1995, then passed H.R. 2126 in lieu on

Microwave Palaeointensity Experiments On Terrestrial and Martian Material

NASA Astrophysics Data System (ADS)

Shaw, J.; Hill, M.; Gratton, M.

The microwave palaeointensity technique was developed in Liverpool University (Walton et al 1996) and has successfully been applied to archaeological ceramics and recent lavas (Shaw et al 1996, 1999.; Hill et al 1999,2000). These published results show that microwave analysis provides accurate palaeointensity determinations com- bined with a very high success rate. Most recently the technique has been successfully applied to Martian material (Shaw et al, 2001) to look for the existence of an internal Martian dynamo early in Martian history. New experiments have been carried out us- ing microwaves to demagnetise synthetic muti-component TRM's and new palaeoin- tensity experiments providing a comparison between microwave analysis of laboratory TRM's and conventional thermal Thellier analysis of microwave generated mTRM's. These experiments demonstrate the equivalence of microwave and thermally gener- ated TRM's. D. Walton, S Snape, T.C. Rolph, J. Shaw and J.A. Share, Application of ferromagnetic resonance heating to palaeointensity determinations.1996, Phys Earth Planet Int,94, 183-186. J. Shaw, D. Walton, S Yang, T.C.Rolph, and J.A. Share. Microwave Archaeointensities from Peruvian Ceramics. 1996, Geophys. J. Int,124,241-244 J. Shaw, S. Yang, T. C. Rolph, and F. Y. Sun. A comparison of archaeointensity results from Chinese ceramics using Microwave and conventional ThellierSs and ShawSs methods.,1999, G J Int.136, 714-718 M. Hill, and J. Shaw, 1999, Palaeointensity results for Historic Lavas from Mt. Etna using microwave demagnetisation/remagnetisation in a modified Thellier type exper- iment. G. J. Int, 139, 583-590 M. J. Hill, and J. Shaw, 2000. Magnetic field intensity study of the 1960 Kilauea lava flow, Hawaii, using the microwave palaeointensity technique, Geophys. J. Int., 142, 487-504. J. Shaw, M. Hill, and S. J. Openshaw, 2001, Investigating the ancient Martian magnetic field using microwaves, Earth and Planetary Science Letters 190 (2001) 103-109

A comparison study on various low energy sources in interstitial prostate brachytherapy

PubMed Central

Bakhshabadi, Mahdi; Ghorbani, Mahdi; Knaup, Courtney; Meigooni, Ali S.

2016-01-01

Purpose Low energy sources are routinely used in prostate brachytherapy. 125I is one of the most commonly used sources. Low energy 131Cs source was introduced recently as a brachytherapy source. The aim of this study is to compare dose distributions of 125I, 103Pd, and 131Cs sources in interstitial brachytherapy of prostate. Material and methods ProstaSeed 125I brachytherapy source was simulated using MCNPX Monte Carlo code. Additionally, two hypothetical sources of 103Pd and 131Cs were simulated with the same geometry as the ProstaSeed 125I source, while having their specific emitted gamma spectra. These brachytherapy sources were simulated with distribution of forty-eight seeds in a phantom including prostate. The prostate was considered as a sphere with radius of 1.5 cm. Absolute and relative dose rates were obtained in various distances from the source along the transverse and longitudinal axes inside and outside the tumor. Furthermore, isodose curves were plotted around the sources. Results Analyzing the initial dose profiles for various sources indicated that with the same time duration and air kerma strength, 131Cs delivers higher dose to tumor. However, relative dose rate inside the tumor is higher and outside the tumor is lower for the 103Pd source. Conclusions The higher initial absolute dose in cGy/(h.U) of 131Cs brachytherapy source is an advantage of this source over the others. The higher relative dose inside the tumor and lower relative dose outside the tumor for the 103Pd source are advantages of this later brachytherapy source. Based on the total dose the 125I source has advantage over the others due to its longer half-life. PMID:26985200

A comparison study on various low energy sources in interstitial prostate brachytherapy.

PubMed

Bakhshabadi, Mahdi; Ghorbani, Mahdi; Khosroabadi, Mohsen; Knaup, Courtney; Meigooni, Ali S

2016-02-01

Low energy sources are routinely used in prostate brachytherapy. (125)I is one of the most commonly used sources. Low energy (131)Cs source was introduced recently as a brachytherapy source. The aim of this study is to compare dose distributions of (125)I, (103)Pd, and (131)Cs sources in interstitial brachytherapy of prostate. ProstaSeed (125)I brachytherapy source was simulated using MCNPX Monte Carlo code. Additionally, two hypothetical sources of (103)Pd and (131)Cs were simulated with the same geometry as the ProstaSeed (125)I source, while having their specific emitted gamma spectra. These brachytherapy sources were simulated with distribution of forty-eight seeds in a phantom including prostate. The prostate was considered as a sphere with radius of 1.5 cm. Absolute and relative dose rates were obtained in various distances from the source along the transverse and longitudinal axes inside and outside the tumor. Furthermore, isodose curves were plotted around the sources. Analyzing the initial dose profiles for various sources indicated that with the same time duration and air kerma strength, (131)Cs delivers higher dose to tumor. However, relative dose rate inside the tumor is higher and outside the tumor is lower for the (103)Pd source. The higher initial absolute dose in cGy/(h.U) of (131)Cs brachytherapy source is an advantage of this source over the others. The higher relative dose inside the tumor and lower relative dose outside the tumor for the (103)Pd source are advantages of this later brachytherapy source. Based on the total dose the (125)I source has advantage over the others due to its longer half-life.

A novel Tc-99m and fluorescence labeled peptide as a multimodal imaging agent for targeting angiogenesis in a murine hindlimb ischemia model.

PubMed

Hyoun Kim, Myoung; Kim, Seul-Gi; Guhn Kim, Chang; Kim, Dae-Weung

2017-03-01

The serine-aspartic acid-valine (SDV) peptide binds specifically to integrin αvβ3. We developed a Tc-99m and TAMRA labeled peptide, Tc-99m SDV-ECG-K-TAMRA for multimodal imaging of angiogenesis. Tc-99m SDV-ECG-K-TAMRA was prepared in high yield (>96%) and showed low cytotoxicity. Tc-99m tetrofosmin images 1 week after operation, revealed significantly decreased perfusion of the ischemic hindlimb, and the perfusion recovered gradually for 4 weeks. In contrast, Tc-99m SDV-ECG-K-TAMRA uptake was maximal 1 week after the operation (ischemic-to-non-ischemic uptake ratio =5.03±1.01) and decreased gradually. The ischemic-to-non-ischemic ratio of Tc-99m SDV-ECG-K-TAMRA and Tc-99m tetrofosmin was strongly negatively correlated (r =-0.94). A postmortem analysis revealed increased angiogenesis markers and uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Our in vivo and in vitro studies revealed substantial uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Tc-99m SDV-ECG-K-TAMRA could be a good candidate dual-modality imaging agent to assess angiogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Windshear Case Study: Denver, Colorado, July 11, 1988

DTIC Science & Technology

1989-11-01

04/03/88 JR) GTF 1850 120 SC.T 250 -OVC: 45 032/83/40/n7/973/TC -.W 04COAS NE-E AND SW-NW GTF 1750 200 -SCT 250 -OVC 45 041/81/48/1306/?76/ ACCAS NE...2104/96) P: WND ; 000 /WSHFT 04 ACCAS S+W RS 1848 ----------------- ENROLITE TERMINAL FORECASTS:----------------- OMA FT11 111717 80 SCT 250 -BKN...Llvina TZz:i - 17 2 I / WPOMI 07/11/10 )ffZ=: 22:09:0@ @ ffM : 22: 09: 0 me! up or:p or -0 SA MR a I,92 - - , . va://94 7t2 18i1:S OA~tR 07/1/m w MInqu

Tc-99m Radiolabeled Peptide p5 + 14 is an Effective Probe for SPECT Imaging of Systemic Amyloidosis.

PubMed

Kennel, Stephen J; Stuckey, Alan; McWilliams-Koeppen, Helen P; Richey, Tina; Wall, Jonathan S

2016-08-01

Systemic peripheral amyloidosis is a rare disease in which misfolded proteins deposit in various organs. We have previously developed I-124 labeled peptide p5 + 14 as a tracer for positron emission tomography imaging of amyloid in patients. In this report, we now document the labeling efficiency, bioactivity, and stability of Tc-99m labeled p5 + 14 for single-photon emission computed tomography (SPECT) imaging of amyloidosis, validated in a mouse model of systemic amyloidosis. Radiochemical yield, purity, and biological activity of [(99m)Tc]p5 + 14 were documented by instant thin-layer chromatography (ITLC), SDS-PAGE and a quantitative amyloid fibril pulldown assay. The efficacy and stability were documented in serum amyloid protein A (AA) amyloid-bearing or wild-type (WT) control mice imaged with SPECT/X-ray computed tomography (CT) at two time points. The uptake and retention of [(99m)Tc]p5 + 14 in hepatosplenic amyloid was evaluated using region of interest (ROI) and tissue counting measurements. Tc-99m p5 + 14 was produced with a radiochemical yield of 75 % with greater than 90 % purity and biological activity comparable to that of radioiodinated peptide. AA amyloid was visualized by SPECT/CT imaging with specific uptake seen in amyloid-laden organs at levels ∼5 folds higher than in healthy mice. ROI analyses of decay-corrected SPECT/CT images showed <20 % loss of radiolabel from the 1 to 4 h imaging time points. Biodistribution data confirmed the specificity of the probe accumulation by amyloid-laden organs as compared to non-diseased tissues. [(99m)Tc]p5 + 14 is a specific and stable radiotracer for systemic amyloid in mice and may provide a convenient and inexpensive alternative to imaging of peripheral amyloidosis in patients.

Comparison of primary position measurements and abduction deficit between type 1 Duane syndrome and sixth cranial nerve palsy.

PubMed

Batra, Noopur Nikki; Arnoldi, Kyle; Reynolds, James D; Strominger, Mitchell B

2011-06-01

Unilateral Duane retraction syndrome type 1 (DRS-I) and unilateral sixth nerve palsy (6NP) present with limitation of abduction, incomitant esotropia, and frequently, a compensatory head turn. The purpose of this study was to compare the mean primary position measurement and to correlate this with the abduction deficit to determine if these measurements may be used to differentiate between the 2 conditions when other clinical signs of DRS-I (globe retraction, changes in lid fissure height, and upshoots/downshoots) are subtle. A database search of patients examined over a 5-year period revealed 69 cases of DRS-I and 62 cases of unilateral 6NP. Primary position measurements both at distance and near and limitation of abduction on version testing were recorded and compared. Mean abduction deficit was -3.5 ± 0.1 for DRS-I and -2.6 ± 0.2 for 6NP (P = 0.0004). Mean esotropia at near was 8.4 ± 1.1 prism diopters (PD) for DRS-I and 27.2 ± 2.4 PD for 6NP (P < 0.0001). Mean esotropia at distance was 10.3 ± 1.3 PD for DRS-I and 36.4 ± 2.4 PD for 6NP (P < 0.0001). The mean distance-near disparity for DRS-I was 1.94 ± 0.62 PD and 9.19 ± 1.28 PD for 6NP (P < 0.0001). The age-group of ≤2 years consisted of 23 DRS-I and only 2 6NP cases. The age-group between >2 years and <18 years had 41 DRS-I and 16 6NP cases, respectively. Finally, the age-group of ≥18 years had only 5 DRS-I and 44 6NP cases (P < 0.0001). Patients with DRS-I showed greater abduction deficit yet significantly less esotropia in primary position than those with 6NP. Patients with 6NP were more likely to have a significant distance-near disparity. In addition, patients with DRS-I tended to be younger than those with 6NP. This report documents that DRS-I and 6NP can be differentiated based on magnitude of primary position esotropia, comparison of primary position esotropia with severity of abduction deficit, distance-near disparity, and patient age.

Electronic Structure, Mechanical and Dynamical Stability of Hexagonal Subcarbides M2C (M = Tc, Ru, Rh, Pd, Re, Os, Ir, and Pt): Ab Initio Calculations

NASA Astrophysics Data System (ADS)

Suetin, D. V.; Shein, I. R.

2018-02-01

Ab initio calculations were used to study the properties of a series of hexagonal (Fe2N-like) subcarbides M2C, where M = Tc, Ru, Rh, Pd, Re, Os, Ir, and Pt, and to calculate their equilibrium structural parameters, electronic properties, phase stability, elastic constants, compression modulus, shear modulus, Young's modulus, compressibility, Pugh's indicator, Poisson ratio, elastic anisotropy indices, and also hardness, Debye temperature, sound velocity, and low-temperature heat capacity. It is found based on these results that all the subcarbides are mechanically stable; however, their formation energies E form are positive with respect to a mixture of d-metal and graphite. In addition, the calculation of the phonon spectra of these subcarbides shows the existence of negative modes, which indicates their dynamical instability. Thus, a successful synthesis of these subcarbides at normal conditions is highly improbable.

FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1-Selected Patients with Non-Small-Cell Lung Cancer.

PubMed

Spigel, David R; Chaft, Jamie E; Gettinger, Scott; Chao, Bo H; Dirix, Luc; Schmid, Peter; Chow, Laura Q M; Hicks, Rodney J; Leon, Larry; Fredrickson, Jill; Kowanetz, Marcin; Sandler, Alan; Funke, Roel; Rizvi, Naiyer A

2018-05-15

The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced non-small-cell lung cancer (NSCLC) selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into Cohort 1 (chemotherapy-naïve/>6 months between adjuvant chemotherapy and recurrence), Cohort 2 (≥ second-line without brain metastases), or Cohort 3 (≥ second-line with treated brain metastases). Patients received 1200 mg atezolizumab, Day 1 (21-day cycles). Primary endpoint: investigator-assessed modified Response Evaluation Criteria in Solid Tumors (mRECIST), objective response rate (ORR; RECIST v1.1). Secondary endpoints: overall survival, progression-free survival, duration of response, safety. Patients (n=138) were enrolled (137 evaluable for response: Cohort 1, n=31; Cohort 2, n=93; Cohort 3, n=13). Investigator-assessed ORR was 32%, 21%, and 23% for Cohorts 1, 2, and 3, respectively. Treatment-related adverse events (TRAEs) were reported in 81%, 67%, and 69% of patients, respectively, including grade 3-4 TRAEs in 16%, 19%, and 15%. Moreover, 88.6% (n=86/97) paired baseline tumor samples had <5% change in TC/IC PD-L1 expression over time. Atezolizumab monotherapy showed clinical activity in patients with NSCLC, including those with brain metastases; safety was consistent with previous trials. Atezolizumab has completed phase III monotherapy studies in second-line; front-line trials are ongoing, confirming these favorable results. Copyright © 2018. Published by Elsevier Inc.

TC-1 Overexpression Promotes Cell Proliferation in Human Non-Small Cell Lung Cancer that Can Be Inhibited by PD173074

PubMed Central

Zhang, Na; Bai, Guangzhen; Zhong, Daixing; Su, Kai; Liu, Boya; Li, Xiaofei; Wang, Yunjie; Wang, Xiaoping

2014-01-01

Thyroid cancer-1 (TC-1), a natively disordered protein, is widely expressed in vertebrates and overexpressed in many kinds of tumors. However, its exact role and regulation mechanism in human non-small cell lung cancer (NSCLC) are still unclear. In the present study, we found that TC-1 is highly expressed in NSCLC and that its aberrant expression is strongly associated with NSCLC cell proliferation. Exogenous TC-1 overexpression promotes cell proliferation, accelerates the cell G1-to-S-phase transition, and reduces apoptosis in NSCLC. The knockdown of TC-1, however, inhibits NSCLC cell proliferation, cycle transition, and apoptosis resistance. Furthermore, we also demonstrated that PD173074, which functions as an inhibitor of the TC-1 in NSCLC, decreases the expression of TC-1 and inhibits TC-1 overexpression mediated cell proliferation in vitro and in vivo. Nevertheless, the inhibition function of PD173074 on NSCLC cell proliferation was eliminated in cells with TC-1 knockdown. These results suggest that PD173074 plays a significant role in TC-1 overexpression mediated NSCLC cell proliferation and may be a potential intervention target for the prevention of cell proliferation in NSCLC. PMID:24941347

Polymer gel water equivalence and relative energy response with emphasis on low photon energy dosimetry in brachytherapy

NASA Astrophysics Data System (ADS)

Pantelis, E.; Karlis, A. K.; Kozicki, M.; Papagiannis, P.; Sakelliou, L.; Rosiak, J. M.

2004-08-01

The water equivalence and stable relative energy response of polymer gel dosimeters are usually taken for granted in the relatively high x-ray energy range of external beam radiotherapy based on qualitative indices such as mass and electron density and effective atomic number. However, these favourable dosimetric characteristics are questionable in the energy range of interest to brachytherapy especially in the case of lower energy photon sources such as 103Pd and 125I that are currently utilized. In this work, six representative polymer gel formulations as well as the most commonly used experimental set-up of a LiF TLD detector-solid water phantom are discussed on the basis of mass attenuation and energy absorption coefficients calculated in the energy range of 10 keV-10 MeV with regard to their water equivalence as a phantom and detector material. The discussion is also supported by Monte Carlo simulation results. It is found that water equivalence of polymer gel dosimeters is sustained for photon energies down to about 60 keV and no corrections are needed for polymer gel dosimetry of 169Yb or 192Ir sources. For 125I and 103Pd sources, however, a correction that is source-distance dependent is required. Appropriate Monte Carlo results show that at the dosimetric reference distance of 1 cm from a source, these corrections are of the order of 3% for 125I and 2% for 103Pd. These have to be compared with corresponding corrections of up to 35% for 125I and 103Pd and up to 15% even for the 169Yb energies for the experimental set-up of the LiF TLD detector-solid water phantom.

Polymer gel water equivalence and relative energy response with emphasis on low photon energy dosimetry in brachytherapy.

PubMed

Pantelis, E; Karlis, A K; Kozicki, M; Papagiannis, P; Sakelliou, L; Rosiak, J M

2004-08-07

The water equivalence and stable relative energy response of polymer gel dosimeters are usually taken for granted in the relatively high x-ray energy range of external beam radiotherapy based on qualitative indices such as mass and electron density and effective atomic number. However, these favourable dosimetric characteristics are questionable in the energy range of interest to brachytherapy especially in the case of lower energy photon sources such as 103Pd and 125I that are currently utilized. In this work, six representative polymer gel formulations as well as the most commonly used experimental set-up of a LiF TLD detector-solid water phantom are discussed on the basis of mass attenuation and energy absorption coefficients calculated in the energy range of 10 keV-10 MeV with regard to their water equivalence as a phantom and detector material. The discussion is also supported by Monte Carlo simulation results. It is found that water equivalence of polymer gel dosimeters is sustained for photon energies down to about 60 keV and no corrections are needed for polymer gel dosimetry of 169Yb or 192Ir sources. For 125I and 103Pd sources, however, a correction that is source-distance dependent is required. Appropriate Monte Carlo results show that at the dosimetric reference distance of 1 cm from a source, these corrections are of the order of 3% for 125I and 2% for 103Pd. These have to be compared with corresponding corrections of up to 35% for 125I and 103Pd and up to 15% even for the 169Yb energies for the experimental set-up of the LiF TLD detector-solid water phantom.

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

Lee, H.B.; Blaufox, M.D.

Rats with one kidney clamped (2K1C), both kidneys clamped (2K2C), unilaterally nephrectomized with remaining kidney clamped (1K1C), and normals, were studied using /sup 99m/Tc mercaptoacetyltriglycine ((/sup 99m/Tc)MAG-3) and /sup 131/I orthoiodohippurate ((/sup 131/I)OIH). Clearances of (/sup 99m/Tc)MAG-3 and (/sup 131/I)OIH were performed after constricted rats became hypertensive. Clearances were repeated after i.v. Captopril. Clearances of (/sup 99m/Tc)MAG-3 and (/sup 131/I)OIH in normals didn't change significantly after Captopril. Clearances of (/sup 99m/Tc)MAG-3 and (/sup 131/I)OIH decreased insignificantly after Captopril in the 2K2C model. in the 2K1C group, normal kidney clearance increased ((/sup 99m/Tc)MAG-3 p less than 0.01 and (/sup 131/I)OIH pmore » less than 0.025) and clamped kidney clearance decreased after inhibition ((/sup 99m/Tc)MAG-3, p less than 0.01, (/sup 131/I)OIH p less than 0.02). Clearances increased in the 1K1C group after Captopril ((/sup 99m/Tc)MAG-3 p less than 0.0025 and (/sup 131/I)OIH, p less than 0.001). The ratio of (/sup 99m/Tc)MAG-3 to (/sup 131/I)OIH before Captopril was 0.81 and 0.84 after Captopril. Changes in renal function after Captopril depend on the model of renovascular hypertension and possibly the dose administered. Technetium-99m MAG-3 clearance parallels (/sup 131/I)orthoiodohippurate in renovascular hypertension.« less

Ferromagnetism of Pd-Fe (abstract)

NASA Astrophysics Data System (ADS)

Griffith, G.; Carnegie, D. W., Jr.; Claus, H.

1984-03-01

We present new low field ac susceptibility measurements on Pd1-xFex alloys (0.002≤X<0.01). The Curie temperature TC, determined from these measurements, are significantly lower than those previously obtained in higher magnetic fields [G. J. Nieuwenhuys, Adv. Phys. 24, 515 (1975)]. We also found that for a given sample, TC depends very sensitively on its heat treatment. As an example, for an alloy with 0.4 at. % Fe, TC can be varied between 4 and 10 K. In other alloys, like PdNi or RhNi similar changes in TC are due to changes in the degree of atomic short-range order [S. Crane, D. W. Carnegie, Jr., and H. Claus, J. Appl. Phys. 53, 2179 (1982)]. However, for PdFe we show evidence that the changes in TC are due to absorption of small amounts of oxygen, the samples with the highest amount of oxygen having the highest TC. It thus seems that oxygen has the opposite effect from hydrogen on the exchange enhanced susceptibility of Pd [J. A. Mydosh, Phys. Rev. Lett. 33, 1562 (1974)].

99mTc-HYNIC-TOC scintigraphy is superior to 131I-MIBG imaging in the evaluation of extraadrenal pheochromocytoma.

PubMed

Chen, Libo; Li, Fang; Zhuang, Hongming; Jing, Hongli; Du, Yanrong; Zeng, Zhengpei

2009-03-01

In this investigation, the efficacy of scintigraphy using (99m)Tc-labeled hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC) in the evaluation of extraadrenal pheochromocytoma was assessed and compared with (131)I-labeled metaiodobenzylguanidine (MIBG) imaging. Ninety-seven patients who were suspected of having pheochromocytoma but showed no definite adrenal abnormalities on CT were evaluated by both (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging. The results were compared with pathology findings or clinical follow-up. Of 58 patients proven to be without pheochromocytoma, (99m)Tc-HYNIC-TOC and (131)I-MIBG imaging excluded 56 and 58 patients, respectively, rendering a specificity of 96.6% for (99m)Tc-HYNIC-TOC imaging and 100% for (131)I-MIBG imaging. In the evaluation of adrenal pheochromocytoma (14 patients), the sensitivity of (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging was 50% and 85.7%, respectively. However, in the evaluation of extraadrenal pheochromocytomas (25 patients), the sensitivity of (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging was 96.0% and 72.0%, respectively. (99m)Tc-HYNIC-TOC scintigraphy is more sensitive than (131)I-MIBG imaging in the detection of extraadrenal pheochromocytomas.

Fatigue Among Short- and Long-Term Thyroid Cancer Survivors: Results from the Population-Based PROFILES Registry

PubMed Central

Nieuwlaat, Willy-Anne; Oranje, Wilma A.; Haak, Harm R.; van de Poll-Franse, Lonneke V.; Mols, Floortje

2013-01-01

Background The aims of this study were (i) to obtain insight into the prevalence of fatigue among short- and long-term thyroid cancer (TC) survivors, by comparing a sample of TC survivors with an age- and sex-matched normative population, and (ii) to investigate which demographic, clinical, and TC-specific health-related quality of life (HRQoL) characteristics were associated with fatigue. Methods All patients found to have TC between 1990 and 2008, as registered in the Eindhoven Cancer Registry, received a cross-sectional survey on fatigue (Fatigue Assessment Scale), TC-specific HRQoL (THYCA-QoL), and psychological distress (Hospital Anxiety and Depression Scale). The fatigue scores were compared with those of an age- and sex-matched normative population (n=530). Multiple logistic regression analyses were conducted to investigate the independent associations between clinical and demographic characteristics, TC-specific HRQoL, and psychological distress with fatigue. Results Eighty-six percent (n=306) responded. TC survivors were more often classified as fatigued or very fatigued (short-term <5 years: 43%; long-term 5–10 years: 44%; long-term 10–15 years: 47%; long-term >15 years: 39%) compared to the normative population (25%; p<0.001). Anxiety (odds ratio (OR) 1.15, 95% confidence interval [CI] 1.03–1.28) and depression (OR 1.43 [CI 1.22–1.68]) were associated with fatigue, as was also the case for TC-specific neuromuscular (OR 1.03 [CI 1.01–1.06]), concentration (OR 1.03 [CI 1.01–1.06]), and psychological TC-specific HRQoL (OR 1.06 [CI 1.02–1.10]). Conclusion Short- and long-term TC survivors report higher levels of fatigue than an age- and sex-matched normative population do. Both TC-specific HRQoL and psychological distress were associated with fatigue. PMID:23578315

An NTCP Analysis of Urethral Complications from Low Doserate Mono- and Bi-Radionuclide Brachytherapy.

PubMed

Nuttens, V E; Nahum, A E; Lucas, S

2011-01-01

Urethral NTCP has been determined for three prostates implanted with seeds based on (125)I (145 Gy), (103)Pd (125 Gy), (131)Cs (115 Gy), (103)Pd-(125)I (145 Gy), or (103)Pd-(131)Cs (115 Gy or 130 Gy). First, DU(20), meaning that 20% of the urhral volume receive a dose of at least DU(20), is converted into an I-125 LDR equivalent DU(20) in order to use the urethral NTCP model. Second, the propagation of uncertainties through the steps in the NTCP calculation was assessed in order to identify the parameters responsible for large data uncertainties. Two sets of radiobiological parameters were studied. The NTCP results all fall in the 19%-23% range and are associated with large uncertainties, making the comparison difficult. Depending on the dataset chosen, the ranking of NTCP values among the six seed implants studied changes. Moreover, the large uncertainties on the fitting parameters of the urethral NTCP model result in large uncertainty on the NTCP value. In conclusion, the use of NTCP model for permanent brachytherapy is feasible but it is essential that the uncertainties on the parameters in the model be reduced.

Comparative NMR studies of diffusional water permeability of red blood cells from different species: XV. Agile wallaby (Macropus agilis), red-necked wallaby (Macropus rufogriseus) and Goodfellow's tree kangaroo (Dendrolagus goodfellowi).

PubMed

Benga, Gheorghe; Chapman, Bogdan E; Kuchel, Philip W

2009-09-01

The water diffusional permeability (P(d)) of red blood cells (RBC) from agile wallaby (Macropus agilis), red-necked wallaby (Macropus rufogriseus) and Goodfellow's tree kangaroo (Dendrolagus goodfellowi) was monitored using an Mn(2+)-doping (1)H nuclear magnetic resonance (NMR) technique at 400 MHz. The P(d) (cm s(-1)) values of agile wallaby RBCs were 7.5 x 10(-3) at 25 degrees C, 9 x 10(-3) at 30 degrees C, 11 x 10(-3) at 37 degrees C, and 13 x 10(-3) at 42 degrees C. The inhibitory effect of a mercury-containing sulfhydryl (SH)-modifying reagent p-chloromercuribenzoate (PCMB) on agile wallaby RBCs was investigated. The maximal inhibition was reached in 90 min at 37 degrees C with 2 mmol L(-1) PCMB. The value of maximal inhibition was approximately 63% when measured at 25 degrees C, approximately 52% at 37 degrees C and approximately 45% at 42 degrees C. The lowest value of P(d) (corresponding to the basal permeability to water) was approximately 3 x 10(-3) cm s(-1) at 25 degrees C. For the RBCs from red-necked wallaby (M. rufogriseus) the values of P(d) (cm s(-1)) were 7 x 10(-3) at 25 degrees C, 8 x 10(-3) at 30 degrees C, 10 x 10(-3) at 37 degrees C, and 12 x 10(-3) at 42 degrees C. Higher values of P(d) (cm s(-1)) were found for the RBCs from Goodfellow's tree kangaroo (D. goodfellowi): 8.5 x 10(-3) at 25 degrees C, 10 x 10(-3) at 30 degrees C, 13 x 10(-3) at 37 degrees C, and 15 x 10(-3) at 42 degrees C. The mean values of the activation energy of water diffusion (E(a,d)) were approximately 25 kJ mol(-1) for RBCs from the agile wallaby and tree kangaroo, respectively, and approximately 23 kJ mol(-1) for RBCs from red-necked wallaby. The values of E(a,d) increased after exposure of agile wallaby RBCs to PCMB, reaching a value of approximately 43-46 kJ mol(-1) when the maximal inhibition of P(d) was achieved.

47 CFR 73.215 - Contour protection for short-spaced assignments.

Code of Federal Regulations, 2013 CFR

2013-10-01

... station pursuant to 47 CFR 73.211(b)(3): 6 kW ERP/240 meters HAAT—Class A 25 kW ERP/150 meters HAAT—Class B1 50 kW ERP/472 meters HAAT—Class B (b) Applicants requesting short-spaced assignments pursuant to...) C3 to C1 200 (124) 133 (83) 70 (43) C3to C0 215 (134) 152 (94) 81 (50) C3 to C 226 (140) 165 (103) 90...

47 CFR 73.215 - Contour protection for short-spaced assignments.

Code of Federal Regulations, 2012 CFR

2012-10-01

... station pursuant to 47 CFR 73.211(b)(3): 6 kW ERP/240 meters HAAT—Class A 25 kW ERP/150 meters HAAT—Class B1 50 kW ERP/472 meters HAAT—Class B (b) Applicants requesting short-spaced assignments pursuant to...) C3 to C1 200 (124) 133 (83) 70 (43) C3to C0 215 (134) 152 (94) 81 (50) C3 to C 226 (140) 165 (103) 90...

Structure and Properties of fac-[Re(I)(CO)3(NTA)](2-) (NTA(3-) = Trianion of Nitrilotriacetic Acid) and fac-[Re(I)(CO)3(L)](n-) Analogues Useful for Assessing the Excellent Renal Clearance of the fac-[(99m)Tc(I)(CO)3(NTA)](2-) Diagnostic Renal Agent.

PubMed

Klenc, Jeffrey; Lipowska, Malgorzata; Abhayawardhana, Pramuditha L; Taylor, Andrew T; Marzilli, Luigi G

2015-07-06

We previously identified two new agents based on the [(99m)Tc(V)O](3+) core with renal clearances in human volunteers 30% higher than that of the widely used clinical tracer (99m)Tc-MAG3 (MAG3(5-) = penta-anion of mercaptoacetyltriglycine). However, renal agents with even higher clearances are needed. More recently, we changed our focus from the [(99m)Tc(V)O](3+) core to the discovery of superior tracers based on the fac-[(99m)Tc(I)(CO)3](+) core. Compared to (99m)Tc-MAG3, fac-[(99m)Tc(I)(CO)3(NTA)](2-) (NTA(3-) = trianion of nitrilotriacetic acid) holds great promise by virtue of its efficient renal clearance via tubular secretion and the absence of hepatobiliary elimination, even in patients with severely reduced renal function. We report here NMR, molecular (X-ray) structure, and solution data on fac-[Re(I)(CO)3(NTA)](2-) with a -CH2CO2(-) dangling monoanionic chain and on two fac-[Re(I)(CO)3(L)](-) analogues with either a -CH2CONH2 or a -CH2CH2OH dangling neutral chain. In these three fac-[Re(I)(CO)3(L)](n-) complexes, the fac-[Re(I)(CO)3(N(CH2CO2)2)](-) moiety is structurally similar and has similar electronic properties (as assessed by NMR data). In reported and ongoing studies, the two fac-[(99m)Tc(I)(CO)3(L)](-) analogues with these neutral dangling chains were found to have pharmacokinetic properties very similar to those of fac-[(99m)Tc(I)(CO)3(NTA)](2-). Therefore, we reach the unexpected conclusion that in fac-[(99m)Tc(I)(CO)3(L)](n-) agents, renal clearance is affected much more than anticipated by features of the core plus the chelate rings (the [(99m)Tc(I)(CO)3(N(CH2CO2)2)](-) moiety) than by the presence of a negatively charged dangling carboxylate chain.

Performance of TcI/TcVI/TcII Chagas-Flow ATE-IgG2a for universal and genotype-specific serodiagnosis of Trypanosoma cruzi infection

PubMed Central

Alessio, Glaucia Diniz; de Araújo, Fernanda Fortes; Côrtes, Denise Fonseca; Sales Júnior, Policarpo Ademar; Lima, Daniela Cristina; Gomes, Matheus de Souza; do Amaral, Laurence Rodrigues; Xavier, Marcelo Antônio Pascoal; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; de Lana, Marta

2017-01-01

Distinct Trypanosoma cruzi genotypes have been considered relevant for patient management and therapeutic response of Chagas disease. However, typing strategies for genotype-specific serodiagnosis of Chagas disease are still unavailable and requires standardization for practical application. In this study, an innovative TcI/TcVI/TcII Chagas Flow ATE-IgG2a technique was developed with applicability for universal and genotype-specific diagnosis of T. cruzi infection. For this purpose, the reactivity of serum samples (percentage of positive fluorescent parasites-PPFP) obtained from mice chronically infected with TcI/Colombiana, TcVI/CL or TcII/Y strain as well as non-infected controls were determined using amastigote-AMA, trypomastigote-TRYPO and epimastigote-EPI in parallel batches of TcI, TcVI and TcII target antigens. Data demonstrated that “α-TcII-TRYPO/1:500, cut-off/PPFP = 20%” presented an excellent performance for universal diagnosis of T. cruzi infection (AUC = 1.0, Se and Sp = 100%). The combined set of attributes “α-TcI-TRYPO/1:4,000, cut-off/PPFP = 50%”, “α-TcII-AMA/1:1,000, cut-off/PPFP = 40%” and “α-TcVI-EPI/1:1,000, cut-off/PPFP = 45%” showed good performance to segregate infections with TcI/Colombiana, TcVI/CL or TcII/Y strain. Overall, hosts infected with TcI/Colombiana and TcII/Y strains displayed opposite patterns of reactivity with “α-TcI TRYPO” and “α-TcII AMA”. Hosts infected with TcVI/CL strain showed a typical interweaved distribution pattern. The method presented a good performance for genotype-specific diagnosis, with global accuracy of 69% when the population/prototype scenario include TcI, TcVI and TcII infections and 94% when comprise only TcI and TcII infections. This study also proposes a receiver operating reactivity panel, providing a feasible tool to classify serum samples from hosts infected with distinct T. cruzi genotypes, supporting the potential of this method for universal and genotype-specific diagnosis of T. cruzi infection. PMID:28333926

History of the Field Artillery School. Volume 2. World War II

DTIC Science & Technology

1946-10-31

1; FAR TC (B)- I AR MD- I 161 All successful candidates rA-9; INF-11 MC - I, transferred~to Class No. TD -1l; ARMD-. AAF-4; 162. FAPTC M-).4; FA1RTC...FT T brT fUf1 71 -- 4T 4 G Lbug, 8~ 65 2W 1 3 -1"- IT-4P I ’l- -Y -- 44 1f 3c 52 T8 r TOT- 42 ’a- G 2 7 MT~ U’r, Td ~ 41 r - 50 DI 1 41 v 3 4 2...or any other pertinent remarks) lFnlstPd Experience: bei Ia _ ___ -,T- 1tI rh U_ OF ate WIN__ IRS, Admln.ML Unit Grade ___ Dais Map flat Td ftsI Ud

Diagnostic value of 99mTc-ethambutol scintigraphy in tuberculosis: compared to microbiological and histopathological tests.

PubMed

Kartamihardja, A H S; Kurniawati, Y; Gunawan, R

2018-01-01

Tuberculosis (TB) still remains the world's endemic infection. TB affects the lungs and any part of the body other than the lung. The diagnosis of TB has not changed much over the decades. Ethambutol is one of the first line treatments for TB. It can be labeled using 99m Tc. 99m Tc-ethambutol will be accumulated in the site of TB lesion and can be imaged using gamma camera. The aim of this study was to evaluate the diagnostic value of 99m Tc-ethambutol scintigraphy in detecting and localizing of TB. Retrospective cross-sectional study was done. Subjects were patients suspected of having TB infection. Whole body and SPECT-CT imaging at the suspected area was done 1 and 4 h after injection of 370-555 MBq 99m Tc-ethambutol. 99m Tc-ethambutol scintigraphy was analyzed visually. The results were compared with that of histopathological or microbiological tests. Statistical analysis was done to determine the sensitivity, specificity, PPV, NPV and accuracy. One hundred and sixty-eight subjects were involved in this study. There were 110 men and 58 women with mean age of 34.52 ± 11.94 years. There were concordance results in 156 (92.86%) and discordant in 12 (7.14%) subjects between 99m Tc-ethambutol scintigraphy and histopathological or microbiological result. The sensitivity, specificity, PPV, NPV and accuracy of 99m Tc-ethambutol scintigraphy in the diagnosis of pulmonary TB were 93.9, 85.7, 93.9, 85.7 and 91.4%, respectively, for extra-pulmonary TB 95.5, 77.8, 97.9, 63.6, and 85.1%, respectively, and for total tuberculosis 94.9, 83.3, 96.3, 78.1 and 92.8%, respectively. There was no side effect observed in this study. 99m Tc-ethambutol scintigraphy is a useful diagnostic imaging technique to detect and localize intra- and extra-pulmonary TB. It is safe to be performed even in pediatric patient. Consuming ethambutol less than 2 weeks did not influence the result.

Thermodynamics of Palladium (Pd) and Tantalum (Ta) Relevant to Secondary Copper Smelting

NASA Astrophysics Data System (ADS)

Shuva, M. A. H.; Rhamdhani, M. A.; Brooks, G. A.; Masood, S. H.; Reuter, M. A.

2017-02-01

The slag-to-metal distribution ratios of palladium (Pd), L_{{Pd}}^{s/m} , in the range of oxygen partial pressure ( pO2) from 10-10 to 10-7 atm at 1473 K to 1623 K (1200 °C to 1350 °C); distribution ratios of tantalum (Ta), L_{{Ta}}^{s/m} , in the range of pO2 from 10-16 to 10-12 atm at 1673 K and 1873 K (1400 °C and 1600 °C), have been determined in this study. The L_{{Pd}}^{s/m} in FeO x -CaO-SiO2-MgO and copper at 1573 K (1300 °C) and pO2 = 10-8 atm is dependant strongly on basicity of slag, i.e. (CaO + MgO)/SiO2 or optical basicity. The current results suggest that Pd presents in the FeO x -CaO-SiO2-MgO slag predominantly as Pd2+. The activity coefficient of PdO in the slag at 1573 K (1300 °C) and pO2 = 10-8 atm was calculated to be in the range of 3.89 × 10-3 to 2.63 × 10-2. The L_{{Pd}}^{s/m} was also found to increase with increasing of pO2 and with decreasing of temperature. It was observed that Ta mostly partition to slag phase and very small amount of Ta was found in liquid copper at the high temperature and reduced condition studied. It can be suggested that to promote recovery of palladium from Pd-containing e-waste, a slag with lower silica content and basic flux based, high temperature with reducing atmosphere, is highly desired particularly in secondary copper smelting.

(99m)Tc(CO)3(NTA): a (99m)Tc renal tracer with pharmacokinetic properties comparable to those of (131)I-OIH in healthy volunteers.

PubMed

Taylor, Andrew T; Lipowska, Malgorzata; Marzilli, Luigi G

2010-03-01

Studies in rats showed that the pharmacokinetics of the tricarbonyl core radiopharmaceutical (99m)Tc(CO)(3)-nitrilotriacetic acid, (99m)Tc(CO)(3)(NTA), were essentially identical to those of (131)I ortho-iodohippuran ((131)I-OIH), the clinical gold standard for the measurement of effective renal plasma flow. Our objective was to compare the pharmacokinetics of these 2 tracers in healthy volunteers. (99m)Tc(CO)(3)(NTA) was prepared with commercially available NTA and a commercially available kit and isolated by reversed-phase high-performance liquid chromatography. Approximately 74 MBq (2 mCi) of (99m)Tc(CO)(3)(NTA) were coinjected with 9.25 MBq (250 microCi) of (131)I-OIH in 9 volunteers, and simultaneous imaging of each tracer was performed for 24 min. Plasma clearances were determined from 8 blood samples obtained 3-90 min after injection using the single-injection, 2-compartment model. Plasma protein binding, red cell uptake, and percentage injected dose in the urine at 30 and 180 min were determined. There was no difference in the plasma clearances of (99m)Tc(CO)(3)(NTA) and (131)I-OIH, 475 +/- 105 mL/min versus 472 +/- 108 mL/min, respectively. The plasma protein binding and red cell uptake of (99m)Tc(CO)(3)(NTA) were 43% +/- 5% and 9% +/- 6%, respectively; both values were significantly lower (P < 0.001) than the plasma protein binding (75% +/- 3%) and red cell uptake (17% +/- 5%) of (131)I-OIH. There was no significant difference in the percentage injected dose recovered in the urine at 30 min and at 3 h; for comparison, the percentage dose in the urine at 3 h was 91% +/- 4% for (99m)Tc(CO)(3)(NTA) and 91% +/- 6% for (131)I-OIH (P = 0.96). Image quality with (99m)Tc(CO)(3)(NTA) was excellent, and the renogram parameters were similar to those of (131)I-OIH. Preliminary results in healthy volunteers suggest that the pharmacokinetic behavior of (99m)Tc(CO)(3)(NTA) is comparable to that of (131)I-OIH.

Excitation Functions of Helion-Induced Nuclear Reactions for the Production of the Medical Radioisotope 103Pd

NASA Astrophysics Data System (ADS)

Skakun, Ye.; Qaim, S. M.

2005-05-01

Excitation functions were measured by the stacked-foil technique for the reactions 100Ru(α,n)103Pd, 101Ru(α,2n)103Pd, 101Ru(3He,n)103Pd, and 102Ru(3He,2n)103Pd for incident energies up to 25 and 34 MeV for α-particles and 3He ions, respectively. The integral thick target yields of the product radionuclide 103Pd calculated from the excitation functions of the above-named four reactions amount to 960, 1050, 50, and 725 KBq/μAh, respectively, at the maximum energy of the incident particle. The data are compared with the results of statistical model calculations and other charged particle induced reaction investigations.

GATE Simulations of Small Animal SPECT for Determination of Scatter Fraction as a Function of Object Size

NASA Astrophysics Data System (ADS)

Konik, Arda; Madsen, Mark T.; Sunderland, John J.

2012-10-01

In human emission tomography, combined PET/CT and SPECT/CT cameras provide accurate attenuation maps for sophisticated scatter and attenuation corrections. Having proven their potential, these scanners are being adapted for small animal imaging using similar correction approaches. However, attenuation and scatter effects in small animal imaging are substantially less than in human imaging. Hence, the value of sophisticated corrections is not obvious for small animal imaging considering the additional cost and complexity of these methods. In this study, using GATE Monte Carlo package, we simulated the Inveon small animal SPECT (single pinhole collimator) scanner to find the scatter fractions of various sizes of the NEMA-mouse (diameter: 2-5.5 cm , length: 7 cm), NEMA-rat (diameter: 3-5.5 cm, length: 15 cm) and MOBY (diameter: 2.1-5.5 cm, length: 3.5-9.1 cm) phantoms. The simulations were performed for three radionuclides commonly used in small animal SPECT studies:99mTc (140 keV), 111In (171 keV 90% and 245 keV 94%) and 125I (effective 27.5 keV). For the MOBY phantoms, the total Compton scatter fractions ranged (over the range of phantom sizes) from 4-10% for 99mTc (126-154 keV), 7-16% for 111In (154-188 keV), 3-7% for 111In (220-270 keV) and 17-30% for 125I (15-45 keV) including the scatter contributions from the tungsten collimator, lead shield and air (inside and outside the camera heads). For the NEMA-rat phantoms, the scatter fractions ranged from 10-15% (99mTc), 17-23% 111In: 154-188 keV), 8-12% (111In: 220-270 keV) and 32-40% (125I). Our results suggest that energy window methods based on solely emission data are sufficient for all mouse and most rat studies for 99mTc and 111In. However, more sophisticated methods may be needed for 125I.

A Pilot Comparison of 18F-fluorocholine PET/CT, Ultrasonography and 123I/99mTc-sestaMIBI Dual-Phase Dual-Isotope Scintigraphy in the Preoperative Localization of Hyperfunctioning Parathyroid Glands in Primary or Secondary Hyperparathyroidism

PubMed Central

Michaud, Laure; Balogova, Sona; Burgess, Alice; Ohnona, Jessica; Huchet, Virginie; Kerrou, Khaldoun; Lefèvre, Marine; Tassart, Marc; Montravers, Françoise; Périé, Sophie; Talbot, Jean-Noël

2015-01-01

Abstract We compared 18F-fluorocholine hybrid positron emission tomography/X-ray computed tomography (FCH-PET/CT) with ultrasonography (US) and scintigraphy in patients with hyperparathyroidism and discordant, or equivocal results of US and 123I/99mTc-sesta-methoxyisobutylisonitrile (sestaMIBI) dual-phase parathyroid scintigraphy. FCH-PET/CT was performed in 17 patients with primary (n = 11) lithium induced (n = 1) or secondary hyperparathyroidism (1 dialyzed, 4 renal-transplanted). The reference standard was based on results of surgical exploration and histopathological examination. The results of imaging modalities were evaluated, on site and by masked reading, on per-patient and per-lesion bases. In a first approach, equivocal images/foci were considered as negative. On a per-patient level, the sensitivity was for US 38%, for scintigraphy 69% by open and 94% by masked reading, and for FCH-PET/CT 88% by open and 94% by masked reading. On a per-lesion level, sensitivity was for US 42%, for scintigraphy 58% by open and 83% by masked reading, and for FCH-PET/CT 88% by open and 96% by masked reading. One ectopic adenoma was missed by the 3 imaging modalities. Considering equivocal images/foci as positive increased the accuracy of the open reading of scintigraphy or of FCH-PET/CT, but not of US. FCH-PET/CT was significantly superior to US in all approaches, whereas it was more sensitive than scintigraphy only for open reading considering equivocal images/foci as negative (P = 0.04). FCH uptake was more intense in adenomas than in hyperplastic parathyroid glands. Thyroid lesions were suspected in 9 patients. They may induce false-positive results as in one case of oncocytic thyroid adenoma, or false-negative results as in one case of intrathyroidal parathyroid adenoma. Thyroid cancer (4 cases) can be visualized with FCH as with 99mTc-sestaMIBI, but the intensity of uptake was moderate, similar to that of parathyroid hyperplasia. This pilot study confirmed that FCH-PET/CT is an adequate imaging tool in patients with primary or secondary hyperparathyroidism, since both adenomas and hyperplastic parathyroid glands can be detected. The sensitivity of FCH-PET/CT was better than that of US and was not inferior to that of dual-phase dual-isotope 123I/99mTc-scintigraphy. Further studies should evaluate whether FCH could replace 99mTc-sestaMIBI as the functional agent for parathyroid imaging, but US would still be useful to identify thyroid lesions. PMID:26469908

Values of (99m)Tc-methoxyisobutylisonitrile imaging after first-time large-dose (131)I therapy in treating differentiated thyroid cancer.

PubMed

Pan, Xiaomei; Duan, Dong; Zhu, Yuquan; Pang, Hua; Guan, Lili; Lv, Zhixiang

2016-01-01

The aim of this study is to investigate the use of (99m)Tc-methoxyisobutylisonitrile (MIBI) imaging for evaluating the treatment response of differentiated thyroid cancer (DTC) after the first administration of a high dose of (131)I. Patients with DTC who received (131)I therapy underwent (99m)Tc-MIBI imaging after successive increases in the therapeutic dose of (131)I, and the serum levels of thyroglobulin (Tg) were measured. A total of 191 patients were enrolled in the final analysis, including 65 metastases and/or thyroid remnant-positive patients (22 patients with metastases and 43 patients with thyroid remnants). The sensitivity of (99m)Tc-MIBI imaging for detecting positive cases and thyroid remnants was 56.9% and 39.5%, respectively, which was significantly lower than that of (131)I imaging (92.3% and 100%, respectively, P<0.01 for both). The sensitivity of (99m)Tc-MIBI imaging for detecting metastases was 90.9%, which was slightly higher than that of (131)I imaging (77.3%, P>0.05). The Tg levels in the positive group were significantly higher than that in the negative group (P<0.01). In addition, the Tg levels in the (99m)Tc-MIBI(+)/(131)I(-) group were significantly higher than that in the (131)I(+)/(99m)Tc-MIBI group (P<0.05). After the first (131)I therapy, although (99m)Tc-MIBI imaging was able to detect the existence of metastatic lesions in patients with DTC better, its assessment for the removal efficiency of thyroid remnants was unsatisfactory. The results of (99m)Tc-MIBI imaging showed good correlations with the Tg level.

Chemical and biological characterization of technetium(I) and Rhenium(I) tricarbonyl complexes with dithioether ligands serving as linkers for coupling the Tc(CO)(3) and Re(CO)(3) moieties to biologically active molecules.

PubMed

Pietzsch, H J; Gupta, A; Reisgys, M; Drews, A; Seifert, S; Syhre, R; Spies, H; Alberto, R; Abram, U; Schubiger, P A; Johannsen, B

2000-01-01

The organometallic precursor (NEt(4))(2)[ReBr(3)(CO)(3)] was reacted with bidendate dithioethers (L) of the general formula H(3)C-S-CH(2)CH(2)-S-R (R = -CH(2)CH(2)COOH, CH(2)-C&tbd1;CH) and R'-S-CH(2)CH(2)-S-R' (R' = CH(3)CH(2)-, CH(3)CH(2)-OH, and CH(2)COOH) in methanol to form stable rhenium(I) tricarbonyl complexes of the general composition [ReBr(CO)(3)L]. Under these conditions, the functional groups do not participate in the coordination. As a prototypic representative of this type of Re compounds, the propargylic group bearing complex [ReBr(CO(3))(H(3)C-S-CH(2)CH(2)-S-CH(2)C&tbd1;CH)] Re2 was studied by X-ray diffraction analysis. Its molecular structure exhibits a slightly distorted octahedron with facial coordination of the carbonyl ligands. The potentially tetradentate ligand HO-CH(2)CH(2)-S-CH(2)CH(2)-S-CH(2)CH(2)-OH was reacted with the trinitrato precursor [Re(NO(3))(3)(CO)(3)](2-) to yield a cationic complex [Re(CO)(3)(HO-CH(2)CH(2)-S-CH(2)CH(2)-S-CH(2)CH(2)-OH)]NO(3) Re8 which shows the coordination of one hydroxy group. Re8 has been characterized by correct elemental analysis, infrared spectroscopy, capillary electrophoresis, and X-ray diffraction analysis. Ligand exchange reaction of the carboxylic group bearing ligands H(3)C-S-CH(2)CH(2)-S-CH(2)CH(2)-COOH and HOOC-CH(2)-S-CH(2)CH(2)-S-CH(2)-COOH with (NEt(4))(2)[ReBr(3)(CO)(3)] in water and with equimolar amounts of NaOH led to complexes in which the bromide is replaced by the carboxylic group. The X-ray structure analysis of the complex [Re(CO)(3)(OOC-CH(2)-S-CH(2)CH(2)-S-CH(2)-COOH)] Re6 shows the second carboxylic group noncoordinated offering an ideal site for functionalization or coupling a biomolecule. The no-carrier-added preparation of the analogous (99m)Tc(I) carbonyl thioether complexes could be performed using the precursor fac-[(99m)Tc(H(2)O)(3)(CO)(3)](+), with yields up to 90%. The behavior of the chlorine containing (99m)Tc complex [(99m)TcCl(CO)(3)(CH(3)CH(2)-S-CH(2)CH(2)-S-CH(2)CH(3))] Tc1 in aqueous solution at physiological pH value was investigated. In saline, the chromatographically separated compound was stable for at least 120 min. However, in chloride-free aqueous solution, a water-coordinated cationic species Tc1a of the proposed composition [(99m)Tc(H(2)O)(CO)(3)(CH(3)CH(2)-S-CH(2)CH(2)-S-CH(2)CH(3))](+) occurred. The cationic charge of the conversion product was confirmed by capillary electrophoresis. By the introduction of a carboxylic group into the thioether ligand as a third donor group, the conversion could be suppressed and thus the neutrality of the complex preserved. Biodistribution studies in the rat demonstrated for the neutral complexes [(99m)TcCl(CO)(3)(CH(3)CH(2)-S-CH(2)CH(2)-S-CH(2)CH(3))] Tc1 and [(99m)TcCl(CO)(3)(CH(2)-S-CH(2)CH(2)-S-CH(2)-C&tbd1;CH)] Tc2 a significant initial brain uptake (1.03 +/- 0.25% and 0.78 +/- 0.08% ID/organ at 5 min. p.i.). Challenge experiments with glutathione clearly indicated that no transchelation reaction occurs in vivo.

Microstructure characterization of Al matrix composite reinforced with Ti-6Al-4V meshes after compression by scanning electron microscope and transmission electron microscope.

PubMed

Guo, Q; Sun, D L; Han, X L; Cheng, S R; Chen, G Q; Jiang, L T; Wu, G H

2012-02-01

Compressive properties of Al matrix composite reinforced with Ti-6Al-4V meshes (TC4(m)/5A06 Al composite) under the strain rates of 10(-3)S(-1) and 1S(-1) at different temperature were measured and microstructure of composites after compression was characterized by scanning electron microscope (SEM) and transmission electron microscope (TEM). Compressive strength decreased with the test temperature increased and the strain-rate sensitivity (R) of composite increased with the increasing temperature. SEM observations showed that grains of Al matrix were elongated severely along 45° direction (angle between axis direction and fracture surface) and TC4 fibres were sheared into several parts in composite compressed under the strain rate of 10(-3)S(-1) at 25°C and 250°C. Besides, amounts of cracks were produced at the interfacial layer between TC4 fibre and Al matrix and in (Fe, Mn)Al(6) phases. With the compressive temperature increasing to 400°C, there was no damage at the interfacial layer between TC4 fibre and Al matrix and in (Fe, Mn)Al(6) phases, while equiaxed recrystal grains with sizes about 10 μm at the original grain boundaries of Al matrix were observed. However, interface separation of TC4 fibres and Al matrix occurred in composite compressed under the strain rate of 1S(-1) at 250°C and 400°C. With the compressive temperature increasing from 25°C to 100°C under the strain rate of 10(-3) S(-1), TEM microstructure in Al matrix exhibited high density dislocations and slipping bands (25°C), polygonized dislocations and dynamic recovery (100°C), equiaxed recrystals with sizes below 500 μm (250°C) and growth of equiaxed recrystals (400°C), respectively. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparison of SSS and SRS calculated from normal databases provided by QPS and 4D-MSPECT manufacturers and from identical institutional normals.

PubMed

Knollmann, Daniela; Knebel, Ingrid; Koch, Karl-Christian; Gebhard, Michael; Krohn, Thomas; Buell, Ulrich; Schaefer, Wolfgang M

2008-02-01

There is proven evidence for the importance of myocardial perfusion-single-photon emission computed tomography (SPECT) with computerised determination of summed stress and rest scores (SSS/SRS) for the diagnosis of coronary artery disease (CAD). SSS and SRS can thereby be calculated semi-quantitatively using a 20-segment model by comparing tracer-uptake with values from normal databases (NDB). Four severity-degrees for SSS and SRS are normally used: <4, 4-8, 9-13, and > or =14. Manufacturers' NDBs (M-NDBs) often do not fit the institutional (I) settings. Therefore, this study compared SSS and SRS obtained with the algorithms Quantitative Perfusion SPECT (QPS) and 4D-MSPECT using M-NDB and I-NDB. I-NDBs were obtained using QPS and 4D-MSPECT from exercise stress data (450 MBq (99m)Tc-tetrofosmin, triple-head-camera, 30 s/view, 20 views/head) from 36 men with a low post-stress test CAD probability and visually normal SPECT findings. Patient group was 60 men showing the entire CAD-spectrum referred for routine perfusion-SPECT. Stress/rest results of automatic quantification of the 60 patients were compared to M-NDB and I-NDB. After reclassifying SSS/SRS into the four severity degrees, kappa values were calculated to objectify agreement. Mean values (vs M-NDB) were 9.4 +/- 10.3 (SSS) and 5.8 +/- 9.7 (SRS) for QPS and 8.2 +/- 8.7 (SSS) and 6.2 +/- 7.8 (SRS) for 4D-MSPECT. Thirty seven of sixty SSS classifications (kappa = 0.462) and 40/60 SRS classifications (kappa = 0.457) agreed. Compared to I-NDB, mean values were 10.2 +/- 11.6 (SSS) and 6.5 +/- 10.4 (SRS) for QPS and 9.2 +/- 9.3 (SSS) and 7.2 +/- 8.6 (SRS) for 4D-MSPECT. Forty four of sixty patients agreed in SSS and SRS (kappa = 0.621 resp. 0.58). Considerable differences between SSS/SRS obtained with QPS and 4D-MSPECT were found when using M-NDB. Even using identical patients and identical I-NDB, the algorithms still gave substantial different results.

Tc-99m imaging in thyroidectomized differentiated thyroid cancer patients immediately before I-131 treatment.

PubMed

Tsai, Chi-Jung; Cheng, Cheng-Yi; Shen, Daniel Hueng-Yuan; Kuo, Shou Jen; Wang, Lien-Yen; Lee, Chiang-Hsuan; Wang, Jhi-Joung; Chang, Ming-Che; Huang, Wen-Sheng

2016-02-01

The aim of this study was to evaluate the clinical role of technetium-99m pertechnetate (Tc-99m) imaging in thyroidectomized differentiated thyroid cancer patients immediately before radioiodine-131 (I-131) treatment (Tx). Eighty-six consecutive post-total-thyroidectomy patients (15 men, 71 women; mean age: 46.8 years) with pathologically diagnosed differentiated thyroid cancer were retrospectively studied. Tc-99m imaging immediately before I-131 Tx using both patient-based and lesion-based measurements were analyzed and were further compared with those of post-Tx I-131 whole-body scans. For patients with unequivocally positive Tc-99m uptake, the sensitivity was 77% (patient-based) and 59% (site-based). The positive predictive value (PPV) was 100% for both patient-based and site-based measurements. If equivocal Tc-99m uptake was counted as positive, the sensitivity was 83 and 67%, and the PPV was 100 and 99% for patient-based and site-based measurements, respectively. (a) To increase sensitivity yet maintaining high PPV, equivocal Tc-99m uptake should be considered a positive finding. (b) The nearly 100% PPV of Tc-99m imaging immediately before I-131 Tx for remnant detection suggests that Tc-99m imaging not only serves as an alternative to low-dose I-131 scanning in the low-risk post-thyroidectomy patients but also provides a clue for the subsequent I-131 therapeutic dosage and even for the outcome prediction.

2012 ESTCP Live Site Demonstrations Massachusetts Military Reservation Camp Edwards, MA. ESTCP MR-1165 Demonstration Data Report Central Impact Area TEMTADS MP 2x2 Cart Survey

DTIC Science & Technology

2013-01-31

372,250.272 4,618,632.972 0.30 Horizontal Across Track T-004 Blank 372,252.872 4,618,629.872 N/A N/A N/A T-005 Medium ISO 372,255.575 4,618,626.492...4.46 4.89 4.668 0.12 1.33 1.40 1.36 0.03 1.24 1.30 1.27 0.02 Med. ISO 1.69 1.77 1.73 0.031 0.94 1.01 0.98 0.02 0.92 0.96 0.94 0.01 Figure 5-9...1.00 0.5 155mmP -2.70 -0.90 -1.80 0.5 81mmM -3.50 -2.00 -3.00 0.4 Med. ISO 0.80 2.10 1.50 0.4 S ho tp ut 15 5m m P 81 m m M M ed . I S O M ag ne

MicroRNA-124 regulates the expression of MEKK3 in the inflammatory pathogenesis of Parkinson's disease.

PubMed

Yao, Longping; Ye, Yongyi; Mao, Hengxu; Lu, Fengfei; He, Xiaozheng; Lu, Guohui; Zhang, Shizhong

2018-01-12

Parkinson's disease (PD) is the most prevalent neurodegenerative disorder that is characterised by selective loss of midbrain dopaminergic (DA) neurons. Chronic inflammation of the central nervous system is mediated by microglial cells and plays a critical role in the pathological progression of PD. Brain-specific microRNA-124 (miR-124) expression is significantly downregulated in lipopolysaccharide (LPS)-treated BV2 cells and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. However, whether abnormal miR-124 expression could regulate the activation of microglia remains poorly understood. BV2 cells were activated by exposure to LPS, and the expression levels of miR-124, mitogen-activated protein kinase kinase kinase 3 (MEKK3), and the nuclear factor of kappaB (NF-κB) p-p65 were analysed. Over-expression and knockdown studies of miR-124 were performed to observe the effects on MEKK3/NF-κB signalling pathways, and the induction of pro-inflammatory and neurotoxic factors was assessed. In addition, a luciferase reporter assay was conducted to confirm whether MEKK3 is a direct target of miR-124. Meanwhile, production of miR-124, MEKK3, and p-p65; midbrain DA neuronal death; or activation of microglia were analysed when treated with or without miR-124 in the MPTP-induced model of PD. We found that the knockdown of MEKK3 could inhibit the activation of microglia by regulating NF-κB expression. Over-expression of miR-124 could effectively attenuate the LPS-induced expression of pro-inflammatory cytokines and promote the secretion of neuroprotective factors. We also first identified a unique role of miR-124 in mediating the microglial inflammatory response by targeting MEKK3/NF-κB signalling pathways. In the microglial culture supernatant (MCS) transfer model, over-expression of the miR-124 or knockdown of MEKK3 in BV2 cells prevented SH-SY5Y from apoptosis and death. Moreover, MEKK3 and p-p65 were abundantly expressed in the midbrain. Furthermore, their expression levels increased and microglial activation was observed in the MPTP-induced model of PD. In addition, exogenous delivery of miR-124 could suppress MEKK3 and p-p65 expression and attenuate the activation of microglia in the substantia nigra pars compacta of MPTP-treated mice. miR-124 also could prevent MPTP-dependent apoptotic midbrain DA cell death in a MPTP-induced PD model. Taken together, our data suggest that miR-124 can inhibit neuroinflammation in the development of PD by regulating the MEKK3/NF-κB signalling pathways and implicate miR-124 as a potential therapeutic target for regulating the inflammatory response in PD.

Studies of an Optical Multi-Processor Interconnect

DTIC Science & Technology

1994-01-01

that the destinations are uniformly distributed, I is given by (E2k-i 2 k(l -(1 -Pd)i)]ýE) N g -1 i+ ( -- Pd)- +2k- 1 2k - 2’-k’ + k(1 -- (1 -- pd)k...15oo 2000- Number of Nodes Figure 5.16: Variation of Maximum User Throughput with Size I I 94I I I I6 Io•MSe P (snowed) g (dsehd) o𔃺.0 OJU/ I£ 0. 00...curves. Table (6.9) shows that the size and topology of the network does not have any significant effect on the number g of threads needed to keep the

Evaluation of (99)  (m)TcN-MPO as a new myocardial perfusion imaging agent in normal dogs and in an acute myocardial infarction canine model: comparison with (99)  (m)Tc-sestamibi.

PubMed

Bu, Lihong; Li, Renfei; Jin, Zhongnan; Wen, Xiaofei; Liu, Shuang; Yang, Baofeng; Shen, Baozhong; Chen, Xiaoyuan

2011-02-01

(99)  (m)TcN-MPO ([(99)  (m)TcN(mpo)(PNP5)](+): mpo = 2-mercaptopyridine oxide and PNP5 = N-ethoxyethyl-N,N-bis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine) is a cationic (99)  (m)Tc-nitrido complex, which has favorable biodistribution and myocardial uptake with rapid liver clearance in Sprague Dawley rats. The objective of this study was to compare the biodistribution and pharmacokinetics of (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi in normal dogs, and to evaluate the potential of (99)  (m)TcN-MPO as a myocardial perfusion agent in canines with acute myocardial infarction. Five normal mongrel dogs were injected intravenously with (99)  (m)TcN-MPO. Venous blood samples were collected via a femoral vein catheter at 0.5, 1, 2, 3, 4, 5, 10, 20, 30, 40, 60, and 90 min post-injection (p.i.). Anterior-posterior planar images were acquired by γ-camera at 10, 20, 30, 60, 90, and 120 min p.i. Regions of interest (ROIs) were drawn around the heart, liver, and lungs. The heart/liver and heart/lung ratios were calculated by dividing the mean counts in heart ROI by the mean counts in the liver and lung ROI, respectively. For comparison, (99)  (m)Tc-sestamibi was also evaluated in the same five dogs. The interval period between the two examinations was 1 week to eliminate possible interference between these two radiotracers. In addition, single positron emission computed tomography (SPECT) images in the canine infarct model were collected 24 h after myocardial infarction at 30 and 60 min after the administration of (99)  (m)TcN-MPO (n = 4) or (99)  (m)Tc-Sestamibi (n = 4). It was found that (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi displayed very similar blood clearance characteristics during the first 90 min p.i. Both (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi had a rapid blood clearance with less than 50% of initial radioactivity remaining at 1 min and less than 5% at 30 min p.i. (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi both showed good heart/lung contrast. The heart/liver ratio of (99)  (m)TcN-MPO increased with time (0.53 ± 0.06 at 10 min, 0.90 ± 0.062 at 30 min, and 1.22 ± 0.06 at 60 min p.i.), whereas the heart/liver ratio of (99)  (m)Tc-Sestamibi remained low at all time points (0.50 ± 0.03 at 10 min, 0.64 ± 0.03 at 30 min, and 0.60 ± 0.02 at 60 min p.i.). SPECT imaging studies in canines with acute myocardial infarction indicated that good visualization of the left ventricular wall and perfusion defects could be achieved at 30 min after administration of (99)  (m)TcN-MPO but not after (99)  (m)Tc-Sestamibi. The combination of reasonable heart uptake with rapid hepatobiliary excretion makes (99)  (m)TcN-MPO a promising new radiotracer for myocardial perfusion imaging.

Nine different glucose-6-phosphate dehydrogenase (G6PD) variants in a Malaysian population with Malay, Chinese, Indian and Orang Asli (aboriginal Malaysian) backgrounds.

PubMed

Wang, Jichun; Luo, Enjie; Hirai, Makoto; Arai, Meiji; Abdul-Manan, Eas; Mohamed-Isa, Zaleha; Hidayah, Ni; Matsuoka, Hiroyuki

2008-10-01

The Malaysian people consist of several ethnic groups including the Malay, the Chinese, the Indian and the Orang Asli (aboriginal Malaysians). We collected blood samples from outpatients of 2 hospitals in the State of Selangor and identified 27 glucose-6-phosphate dehydrogenase (G6PD)-deficient subjects among these ethnic groups. In the Malay, G6PD Viangchan (871GA, 1311CT, IVS11 nt93TC) and G6PD Mahidol (487GA) types, which are common in Cambodia and Myanmar, respectively, were detected. The Malay also had both subtypes of G6PD Mediterranean:the Mediterranean subtype (563CT, 1311CT, IVS11 nt93TC) and the Indo-Pakistan subtype (563CT, 1311C, IVS11 nt93T). In Malaysians of Chinese background, G6PD Kaiping (1388GA), G6PD Canton (1376GT) and G6PD Gaohe (95AG), which are common in China, were detected. Indian Malaysians possessed G6PD Mediterranean (Indo-Pakistan subtype) and G6PD Namoru (208TC), a few cases of which had been reported in Vanuatu and many in India. Our findings indicate that G6PD Namoru occurs in India and flows to Malaysia up to Vanuatu. We also discovered 5 G6PD-deficient cases with 2 nucleotide substitutions of 1311CT and IVS11 nt93TC, but without amino-acid substitution in the G6PD molecule. These results indicate that the Malaysian people have incorporated many ancestors in terms of G6PD variants.

Dose escalation in permanent brachytherapy for prostate cancer: dosimetric and biological considerations

NASA Astrophysics Data System (ADS)

Li, X. Allen; Wang, Jian Z.; Stewart, Robert D.; Di Biase, Steven J.

2003-09-01

No prospective dose escalation study for prostate brachytherapy (PB) with permanent implants has been reported. In this work, we have performed a dosimetric and biological analysis to explore the implications of dose escalation in PB using 125I and 103Pd implants. The concept of equivalent uniform dose (EUD), proposed originally for external-beam radiotherapy (EBRT), is applied to low dose rate brachytherapy. For a given 125I or 103Pd PB, the EUD for tumour that corresponds to a dose distribution delivered by EBRT is calculated based on the linear quadratic model. The EUD calculation is based on the dose volume histogram (DVH) obtained retrospectively from representative actual patient data. Tumour control probabilities (TCPs) are also determined in order to compare the relative effectiveness of different dose levels. The EUD for normal tissue is computed using the Lyman model. A commercial inverse treatment planning algorithm is used to investigate the feasibility of escalating the dose to prostate with acceptable dose increases in the rectum and urethra. The dosimetric calculation is performed for five representative patients with different prostate sizes. A series of PB dose levels are considered for each patient using 125I and 103Pd seeds. It is found that the PB prescribed doses (minimum peripheral dose) that give an equivalent EBRT dose of 64.8, 70.2, 75.6 and 81 Gy with a fraction size of 1.8 Gy are 129, 139, 150 and 161 Gy for 125I and 103, 112, 122 and 132 Gy for 103Pd implants, respectively. Estimates of the EUD and TCP for a series of possible prescribed dose levels (e.g., 145, 160, 170 and 180 Gy for 125I and 125, 135, 145 and 155 for 103Pd implants) are tabulated. The EUD calculation was found to depend strongly on DVHs and radiobiological parameters. The dosimetric calculations suggest that the dose to prostate can be escalated without a substantial increase in both rectal and urethral dose. For example, increasing the PB prescribed dose from 145 to 180 Gy increases EUD for the rectum by only 3%. Our studies indicate that the dose to urethra can be kept within 100-120% of the prescription dose for all the dose levels studied. In conclusion, dose escalation in permanent implant for localized prostate cancer may be advantageous. It is dosimetrically possible to increase dose to prostate without a substantial increase in the dose to the rectum and urethra. Based on the results of our studies, a prospective dose escalation trial for prostate permanent implants has been initiated at our institution.

Nuclear Data Sheets for A = 91

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

Baglin, Coral M.

2013-10-15

Experimental nuclear structure and decay data for all known A=91 nuclides (As, Se, Br, Kr, Rb, Sr, Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd) have been evaluated. This evaluation, covering data received by 1 September 2013, supersedes the 1998 evaluation by C. M. Baglin published in Nuclear Data Sheets86, 1 (1999) (15 December 1998 literature cutoff), and subsequent evaluations by C. M. Baglin added to the ENSDF database for Kr, Sr and Zr (29 December 2000 literature cutoff) and by B. Singh for {sup 91}Tc (6 November 2000 literature cutoff)

Recent achievements in Tc-99m radiopharmaceutical direct production by medical cyclotrons.

PubMed

Boschi, Alessandra; Martini, Petra; Pasquali, Micol; Uccelli, Licia

2017-09-01

99m Tc is the most commonly used radionuclide in the field of diagnostic imaging, a noninvasive method intended to diagnose a disease, assess the disease state and monitor the effects of treatments. Annually, the use of 99m Tc, covers about 85% of nuclear medicine applications. This isotope releases gamma rays at about the same wavelength as conventional X-ray diagnostic equipment, and owing to its short half-life (t ½  = 6 h) is ideal for diagnostic nuclear imaging. A patient can be injected with a small amount of 99m Tc and within 24 h almost 94% of the injected radionuclide would have decayed and left the body, limiting the patient's radiation exposure. 99m Tc is usually supplied to hospitals through a 99 Mo/ 99m Tc radionuclide generator system where it is produced from the β decay of the parent nuclide 99 Mo (t ½  = 66 h), which is produced in nuclear reactors via neutron fission. Recently, the interruption of the global supply chain of reactor-produced 99 Mo, has forced the scientific community to investigate alternative production routes for 99m Tc. One solution was to consider cyclotron-based methods as potential replacement of reactor-based technology and the nuclear reaction 100 Mo(p,2n) 99m Tc emerged as the most worthwhile approach. This review reports some achievements about 99m Tc produced by medical cyclotrons. In particular, the available technologies for target design, the most efficient extraction and separation procedure developed for the purification of 99m Tc from the irradiated targets, the preparation of high purity 99m Tc radiopharmaceuticals and the first clinical studies carried out with cyclotron produced 99m Tc are described.

Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology

PubMed Central

Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody

2015-01-01

Purpose Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Material and methods Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: 125I fixed spacing, 125I variable spacing, 103Pd fixed spacing, and 103Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. Results All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with 103Pd, and 0.007 and 0.029 with 125I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with 103Pd, and 0.012 and 0.037 with 125I plans. Conclusions The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy. PMID:26622227

Brachytherapy dosimetry of 125I and 103Pd sources using an updated cross section library for the MCNP Monte Carlo transport code.

PubMed

Bohm, Tim D; DeLuca, Paul M; DeWerd, Larry A

2003-04-01

Permanent implantation of low energy (20-40 keV) photon emitting radioactive seeds to treat prostate cancer is an important treatment option for patients. In order to produce accurate implant brachytherapy treatment plans, the dosimetry of a single source must be well characterized. Monte Carlo based transport calculations can be used for source characterization, but must have up to date cross section libraries to produce accurate dosimetry results. This work benchmarks the MCNP code and its photon cross section library for low energy photon brachytherapy applications. In particular, we calculate the emitted photon spectrum, air kerma, depth dose in water, and radial dose function for both 125I and 103Pd based seeds and compare to other published results. Our results show that MCNP's cross section library differs from recent data primarily in the photoelectric cross section for low energies and low atomic number materials. In water, differences as large as 10% in the photoelectric cross section and 6% in the total cross section occur at 125I and 103Pd photon energies. This leads to differences in the dose rate constant of 3% and 5%, and differences as large as 18% and 20% in the radial dose function for the 125I and 103Pd based seeds, respectively. Using a partially updated photon library, calculations of the dose rate constant and radial dose function agree with other published results. Further, the use of the updated photon library allows us to verify air kerma and depth dose in water calculations performed using MCNP's perturbation feature to simulate updated cross sections. We conclude that in order to most effectively use MCNP for low energy photon brachytherapy applications, we must update its cross section library. Following this update, the MCNP code system will be a very effective tool for low energy photon brachytherapy dosimetry applications.

Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology.

PubMed

Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody; Song, Daniel Y

2015-08-01

Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: (125)I fixed spacing, (125)I variable spacing, (103)Pd fixed spacing, and (103)Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with (103)Pd, and 0.007 and 0.029 with (125)I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with (103)Pd, and 0.012 and 0.037 with (125)I plans. The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy.

Endogenous cannabinoids induce fever through the activation of CB1 receptors

PubMed Central

Fraga, D; Zanoni, CIS; Rae, GA; Parada, CA; Souza, GEP

2009-01-01

Background and purpose: The effects of centrally administered cannabinoids on body core temperature (Tc) and the contribution of endogenous cannabinoids to thermoregulation and fever induced by lipopolysaccharide (LPS) (Sigma Chem. Co., St. Louis, MO, USA) were investigated. Experimental approach: Drug-induced changes in Tc of male Wistar rats were recorded over 6 h using a thermistor probe (Yellow Springs Instruments 402, Dayton, OH, USA) inserted into the rectum. Key results: Injection of anandamide [(arachidonoylethanolamide (AEA); Tocris, Ellisville, MO, USA], 0.01–1 µg i.c.v. or 0.1–100 ng intra-hypothalamic (i.h.), induced graded increases in Tc (peaks 1.5 and 1.6°C at 4 h after 1 µg i.c.v. or 10 ng i.h.). The effect of AEA (1 µg, i.c.v.) was preceded by decreases in tail skin temperature and heat loss index (values at 1.5 h: vehicle 0.62, AEA 0.48). Bell-shaped curves were obtained for the increase in Tc induced by the fatty acid amide hydrolase inhibitor [3-(3-carbamoylphenyl)phenyl] N-cyclohexylcarbamate (Cayman Chemical Co., Ann Arbor, MI, USA) (0.001–1 ng i.c.v.; peak 1.9°C at 5 h after 0.1 ng) and arachidonyl-2-chloroethylamide (ACEA; Tocris) (selective CB1 agonist; 0.001–1 µg i.c.v.; peak 1.4°C 5 h after 0.01 µg), but (R,S)-(+)-(2-Iodo-5-nitrobenzoyl)-[1-(1-methyl-piperidin-2-ylmethyl)-1H-indole-3-yl] methanone (Tocris) (selective CB2 agonist) had no effect on Tc. AEA-induced fever was unaffected by i.c.v. pretreatment with 6-Iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indole-3-yl](4-methoxyphenyl) methanone (Tocris) (selective CB2 antagonist), but reduced by i.c.v. pretreatment with N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251; Tocris) (selective CB1 antagonist). AM251 also reduced the fever induced by ACEA or LPS. Conclusions and implications: The endogenous cannabinoid AEA induces an integrated febrile response through activation of CB1 receptors. Endocannabinoids participate in the development of the febrile response to LPS constituting a target for antipyretic therapy. PMID:19681872

Monte Carlo dosimetry for {sup 103}Pd, {sup 125}I, and {sup 131}Cs ocular brachytherapy with various plaque models using an eye phantom

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

Lesperance, Marielle; Martinov, M.; Thomson, R. M., E-mail: rthomson@physics.carleton.ca

Purpose: To investigate dosimetry for ocular brachytherapy for a range of eye plaque models containing{sup 103}Pd, {sup 125}I, or {sup 131}Cs seeds with model-based dose calculations. Methods: Five representative plaque models are developed based on a literature review and are compared to the standardized COMS plaque, including plaques consisting of a stainless steel backing and acrylic insert, and gold alloy backings with: short collimating lips and acrylic insert, no lips and silicone polymer insert, no lips and a thin acrylic layer, and individual collimating slots for each seed within the backing and no insert. Monte Carlo simulations are performed usingmore » the EGSnrc user-code BrachyDose for single and multiple seed configurations for the plaques in water and within an eye model (including nonwater media). Simulations under TG-43 assumptions are also performed, i.e., with the same seed configurations in water, neglecting interseed and plaque effects. Maximum and average doses to ocular structures as well as isodose contours are compared for simulations of each radionuclide within the plaque models. Results: The presence of the plaque affects the dose distribution substantially along the plaque axis for both single seed and multiseed simulations of each plaque design in water. Of all the plaque models, the COMS plaque generally has the largest effect on the dose distribution in water along the plaque axis. Differences between doses for single and multiple seed configurations vary between plaque models and radionuclides. Collimation is most substantial for the plaque with individual collimating slots. For plaques in the full eye model, average dose in the tumor region differs from those for the TG-43 simulations by up to 10% for{sup 125}I and {sup 131}Cs, and up to 17% for {sup 103}Pd, and in the lens region by up to 29% for {sup 125}I, 34% for {sup 103}Pd, and 28% for {sup 131}Cs. For the same prescription dose to the tumor apex, the lowest doses to critical ocular structures are generally delivered with plaques containing {sup 103}Pd seeds. Conclusions: The combined effects of ocular and plaque media on dose are significant and vary with plaque model and radionuclide, suggesting the importance of model-based dose calculations employing accurate ocular and plaque media and geometries for eye plaque brachytherapy.« less

Effects of tricyclazole (5-methyl-1,2,4-triazol[3,4] benzothiazole), a specific DHN-melanin inhibitor, on the morphology of Fonsecaea pedrosoi conidia and sclerotic cells.

PubMed

Franzen, Anderson J; Cunha, Marcel M L; Batista, Evander J O; Seabra, Sergio H; De Souza, Wanderley; Rozental, Sonia

2006-09-01

The influence of tricyclazole (5-methyl-1,2,4-triazol[3,4]benzothiazole), a specific DHN-melanin inhibitor, on the cell walls and intracellular structures of Fonsecaea pedrosoi conidia and sclerotic cells was analyzed by transmission electron microscopy (TEM), deep-etching, and field emission scanning electron microscopy. The treatment of the fungus with 16 microg mL(-1) of tricyclazole (TC) did not significantly affect fungal viability, but electron microscopy observations showed several important morphological differences between TC-treated and non-TC treated cells. Control sclerotic cells presented patched granules, with an average diameter of 47 nm, on the cell surface, which were absent in TC-treated cells. Also, TC-treated sclerotic cells showed an undulated relief. TC treatment leads to an accumulation of electron lucent vacuoles in the fungal cytoplasm of both conidia and sclerotic cells, and treated conidia observed by deep etching showed a relevant thickening of the fungal cell wall. Together, these observations support the previous data of our group that F. pedrosoi synthesizes melanin in intracellular organelles. In addition, we suggest that melanin is not only an extracellular constituent but could also be dispersing all over the cell walls and could have an effective role in cross-linking different cell wall compounds that help maintain the regular shape of the cell wall. (c) 2006 Wiley-Liss, Inc.

Producing radiometals in liquid targets: Proof of feasibility with {sup 94m}Tc

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

Hoehr, C.; Badesso, B.; Morley, T.

2012-12-19

{sup 94m}Tc was produced in a liquid target loaded with a molybdenum-salt solution. This novel technique allows for the irradiation of metals dissolved in a liquid solution, normally only available in metal powder or foil form. By using this approach, the existing liquid targets and transfer infrastructure of many PET cyclotrons can be used to produce radiometals, avoiding the need, expense and challenges of operating solid targets. Such an approach allows for rapid testing of new isotopes for proof of feasibility studies. Different concentrations of Mo solution and their effect on the target performance were tested. Sufficient quantities to allowmore » for preclinical studies were produced.« less

Clinicopathological features of 22C3 PD-L1 expression with mismatch repair, Epstein-Barr virus status, and cancer genome alterations in metastatic gastric cancer.

PubMed

Kawazoe, Akihito; Shitara, Kohei; Kuboki, Yasutoshi; Bando, Hideaki; Kojima, Takashi; Yoshino, Takayuki; Ohtsu, Atsushi; Ochiai, Atsushi; Togashi, Yosuke; Nishikawa, Hiroyoshi; Doi, Toshihiko; Kuwata, Takeshi

2018-06-01

Recently, the U.S. Food and Drug Administration approved pembrolizumab for patients (pts) with PD-L1-positive metastatic gastric cancer (MGC) based on 22C3 immunohistochemistry (IHC) assay. However, little is known about detailed clinicopathological features of 22C3 PD-L1 expression in MGC. Pts with histologically confirmed MGC were eligible for this prospective observational study. PD-L1 expression (22C3) on tumor cell (TC) or immune cell (IC) and mismatch repair (MMR) were analyzed by IHC. Epstein-Barr virus (EBV) was detected by in situ hybridization. The expressions of tyrosine kinase receptors (RTKs) and cancer genome alterations were evaluated by IHC or next-generation sequencing. A total of 225 pts were analyzed in this study. PD-L1 expression on TC, PD-L1 on IC, MMR-deficient (D-MMR), and EBV positivity were identified in 8.4, 65.3, 6.2, and 6.2% cases, respectively. PD-L1 expression in TC was more frequently observed in pts with D-MMR (P < 0.001), PIK3CA mutation (P = 0.020), and KRAS mutation (P = 0.002), and PD-L1 on IC was associated with EBV positivity (P = 0.034), and lymph-node metastasis (P < 0.001). PD-L1 expression on either IC or TC was less frequently observed in pts with peritoneal metastasis and Borrmann Type 4. A significant association was not observed between PD-L1 expression and RTKs expression or presence of other gene alterations. PD-L1 expression on either TC or IC was not prognostic factor. 22C3 PD-L1 expression in MGC was associated with distinct clinicopathological features, but was not a prognostic factor.

Monoanionic 99mTc-tricarbonyl-aminopolycarboxylate complexes with uncharged pendant groups: Radiosynthesis and evaluation as potential renal tubular tracers.

PubMed

Lipowska, Malgorzata; Klenc, Jeffrey; Jarkas, Nashwa; Marzilli, Luigi G; Taylor, Andrew T

2017-04-01

99m Tc(CO) 3 -nitrilotriacetic acid, 99m Tc(CO) 3 (NTA), is a new renal tubular agent with pharmacokinetic properties comparable to those of 131 I-OIH but the clearance of 99m Tc(CO) 3 (NTA) and 131 I-OIH is still less than the clearance of PAH, the gold standard for the measurement of effective renal plasma flow. At physiological pH, dianionic 99m Tc(CO) 3 (NTA) has a mononegative inner metal-coordination sphere and a mononegative uncoordinated carboxyl group. To evaluate alternate synthetic approaches, we assessed the importance of an uncoordinated carboxyl group, long considered essential for tubular transport, by evaluating the pharmacokinetics of three analogs with the 99m Tc(CO) 3 (NTA) metal-coordination sphere but with uncharged pendant groups. 99m Tc(CO) 3 complexes with N-(2-acetamido)iminodiacetic acid (ADA), N-(2-hydroxyethyl)iminodiacetic acid (HDA) and N-(fluoroethyl)iminodiacetic acid (FEDA) were prepared using a tricarbonyl kit and isolated by HPLC. The pharmacokinetics were evaluated in Sprague-Dawley rats, with 131 I-OIH as an internal control; urine was analyzed for metabolites. Plasma protein binding and erythrocyte uptake were determined from the 10min blood samples. Re(CO) 3 (FEDA), the analog of 99m Tc(CO) 3 (FEDA), was prepared and characterized. 99m Tc(CO) 3 (ADA), 99m Tc(CO) 3 (HDA) and 99m Tc(CO) 3 (FEDA) were efficiently prepared as a single species with high radiochemical purities (>99%). These new monoanionic 99m Tc(CO) 3 tracers with uncharged dangling groups all showed rapid blood clearance and high specificity for renal excretion. Activity in the urine, as a percent of 131 I-OIH at 10 and 60min, was 96% and 99% for ADA, 96% and 100% for HDA, and 100% and 99% for FEDA, respectively. Each new tracer was excreted unchanged in the urine. The Re(CO) 3 (FEDA) structure adds compelling evidence that such 99m Tc(CO) 3 (NTA) analogs have metal-coordination spheres identical to that of 99m Tc(CO) 3 (NTA). New tracers lacking the negatively charged pendant carboxyl group previously thought to be essential for rapid renal extraction, 99m Tc(CO) 3 (ADA), 99m Tc(CO) 3 (HDA) and 99m Tc(CO) 3 (FEDA), exhibit pharmacokinetics in rats comparable to those of 99m Tc(CO) 3 (NTA) and 131 I-OIH. Furthermore, these encouraging results in rats warrant evaluation of this new tracer type in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

99mTc-N4-[Tyr3]Octreotate Versus 99mTc-EDDA/HYNIC-[Tyr3]Octreotide: an intrapatient comparison of two novel Technetium-99m labeled tracers for somatostatin receptor scintigraphy.

PubMed

Gabriel, Michael; Decristoforo, Clemens; Maina, Theodosia; Nock, Berthold; vonGuggenberg, Elisabeth; Cordopatis, Paul; Moncayo, Roy

2004-02-01

Tetraamine-[Tyr3]octreotate (Demotate) is a somatostatin (SST) analogue that can be easily labeled with 99mTc at high specific activities and showed promising preclinical properties for SST receptor scintigraphy. This study reports on the first intra-patient comparison of 99mTc-Demotate and another 99mTc-labeled SST analogue, 99mTc-EDDA/HYNIC-TOC (HYNIC-TOC). Five patients with carcinoid tumors (n = 2) and endocrine pancreatic tumors (n = 3) were investigated with both radiopharmaceuticals. 99mTc-Demotate rapidly visualized somatostatin receptor positive tumors as early as 15 minutes post-injection (p.i.) with maximum tumor uptake and tumor/organ ratios already 1 hour p.i. Organs of predominant physiological uptake were the spleen and the kidneys with no intestinal excretion detectable up to 24 hours. 99mTc-Demotate exhibited faster pharmacokinetic properties compared to HYNIC-TOC. Tumor/organ ratios at equivalent time points were higher or comparable for 99mTc-Demotate in three patients with a matching scan result. Equivocal findings were observed in two patients, i.e. comparable uptake behavior in larger lesions with differences in smaller ones. 99mTc-Demotate is a promising agent for somatostatin receptor scintigraphy providing images of excellent quality as early as 1 hour after injection.

[Molecular characterization of glucose-6-phosphate dehydrogenase deficiency in the Han and Li nationalities in Hainan, China and identification of a new mutation in human G6PD gene].

PubMed

Cai, W; Filosa, S; Martini, G; Zhou, Y; Zhou, D; Cai, L; Kuang, Y

2001-04-01

To elucidate the molecular basis of G6PD deficiency in the Han and Li nationalities in Hainan, China. Polymerase chain reaction and restriction enzyme digestion were used to screen the mutations 1388G-->A, 1360C-->T, 1024C-->T, 592C-->T, 517T-->C, 493A-->G, 487G-->A, 392G-->T and 95A-->G. Single strand conformation polymorphism analysis was used to screen the other mutations followed by DNA sequencing to characterize the mutations of the samples with abnormal SSCP bands. Of the fifty-nine Han cases with G6PD deficiency, fourteen with 1388G-->A (23.7%), three with 871G-->A(5.1%), one with 835A-->T(1.7%), one with 517T-->C (1.7%), three with 392G-->T(5.1%), and four with 95A-->G(6.8%) were found. Of the thirty-two Li cases with G6PD deficiency, six with 1388G-->A(18.8%), three with 871G-->A(9.4%), and two with 95A-->G(6.3%) were found. A new mutation 835A-->G which causes the substitution of Ala for Thr at 279 in a Han case was identified and named as G6PD Haikou. The enzyme activity of the variant is about 10% of the normal and lower than the activity of the variant 835A-->T with about 40% of the normal. Analysis of the 3D model of human G6PD has revealed that the hydroxyl group of Thr at 279 is a group in maintaining the interaction of the G6PD subunits. The most common mutations of G6PD deficiency in Han and Li nationalities in Hainan are similar. Compared with the mutation spectrum of G6PD gene in the populations in other regions of China, the results indicate that some G6PD gene mutations are widespread in the populations of different regions in the southern part of China. The hydroxyl group of the Thr at 279 of human G6PD may be a necessary group for maintaining the interaction of the G6PD subunits and the enzyme activity.

On determining dose rate constants spectroscopically.

PubMed

Rodriguez, M; Rogers, D W O

2013-01-01

To investigate several aspects of the Chen and Nath spectroscopic method of determining the dose rate constants of (125)I and (103)Pd seeds [Z. Chen and R. Nath, Phys. Med. Biol. 55, 6089-6104 (2010)] including the accuracy of using a line or dual-point source approximation as done in their method, and the accuracy of ignoring the effects of the scattered photons in the spectra. Additionally, the authors investigate the accuracy of the literature's many different spectra for bare, i.e., unencapsulated (125)I and (103)Pd sources. Spectra generated by 14 (125)I and 6 (103)Pd seeds were calculated in vacuo at 10 cm from the source in a 2.7 × 2.7 × 0.05 cm(3) voxel using the EGSnrc BrachyDose Monte Carlo code. Calculated spectra used the initial photon spectra recommended by AAPM's TG-43U1 and NCRP (National Council of Radiation Protection and Measurements) Report 58 for the (125)I seeds, or TG-43U1 and NNDC(2000) (National Nuclear Data Center, 2000) for (103)Pd seeds. The emitted spectra were treated as coming from a line or dual-point source in a Monte Carlo simulation to calculate the dose rate constant. The TG-43U1 definition of the dose rate constant was used. These calculations were performed using the full spectrum including scattered photons or using only the main peaks in the spectrum as done experimentally. Statistical uncertainties on the air kerma/history and the dose rate/history were ≤0.2%. The dose rate constants were also calculated using Monte Carlo simulations of the full seed model. The ratio of the intensity of the 31 keV line relative to that of the main peak in (125)I spectra is, on average, 6.8% higher when calculated with the NCRP Report 58 initial spectrum vs that calculated with TG-43U1 initial spectrum. The (103)Pd spectra exhibit an average 6.2% decrease in the 22.9 keV line relative to the main peak when calculated with the TG-43U1 rather than the NNDC(2000) initial spectrum. The measured values from three different investigations are in much better agreement with the calculations using the NCRP Report 58 and NNDC(2000) initial spectra with average discrepancies of 0.9% and 1.7% for the (125)I and (103)Pd seeds, respectively. However, there are no differences in the calculated TG-43U1 brachytherapy parameters using either initial spectrum in both cases. Similarly, there were no differences outside the statistical uncertainties of 0.1% or 0.2%, in the average energy, air kerma/history, dose rate/history, and dose rate constant when calculated using either the full photon spectrum or the main-peaks-only spectrum. Our calculated dose rate constants based on using the calculated on-axis spectrum and a line or dual-point source model are in excellent agreement (0.5% on average) with the values of Chen and Nath, verifying the accuracy of their more approximate method of going from the spectrum to the dose rate constant. However, the dose rate constants based on full seed models differ by between +4.6% and -1.5% from those based on the line or dual-point source approximations. These results suggest that the main value of spectroscopic measurements is to verify full Monte Carlo models of the seeds by comparison to the calculated spectra.

Initial Evaluation of (99m)Tc(CO)3(ASMA) as a Renal Tracer in Healthy Human Volunteers.

PubMed

Lipowska, Malgorzata; Klenc, Jeffrey; Folks, Russell D; Taylor, Andrew T

2014-09-01

Preclinical studies in rats showed that two of (99m)Tc(CO)3(ASMA) isomers (rac- and L-ASMA) had pharmacokinetic properties equivalent to that of (131)I-OIH, the radiopharmaceutical standard for the measurement of effective renal plasma flow. The aim of this study was to evaluate the pharmacokinetics of (99m)Tc(CO)3(ASMA) isomers in healthy human subjects. Three ASMA ligands (rac-, L- and D-ASMA) were labeled with (99m)Tc(CO)3 using an IsoLink kit (Covidien), and each formed (99m)Tc(CO)3(ASMA) tracer was co-injected with (131)I-OIH into healthy human subjects followed by sequential imaging, plasma clearance measurements and timed urine collection. Plasma protein binding, red cell uptake and percent injected dose in the urine were determined. Urine from each group of volunteers was analyzed for metabolites by HPLC. Image quality was excellent with all three agents. Each (99m)Tc(CO)3(ASMA) preparation was excreted unchanged in the urine. The plasma clearance ratio ((99m)Tc(CO)3(ASMA)/(131)I-OIH) was 81 ± 3 % for D-ASMA compared to only 20 ± 4 % for L-ASMA and 37 ± 7 % for rac-ASMA; the 81 % clearance ratio for D-ASMA isomer is still ∼ 30 % higher than the (99m)Tc-MAG3/(131)I-OIH clearance ratio (∼50-60 %). Red cell uptake was similar for all three tracers (6-9 %), and all tracers had a relatively rapid renal excretion; at 3 h, the (99m)Tc(CO)3(ASMA)/(131)I-OIH urine ratio was 100 ± 3 % for D-ASMA, 80 ± 2 % for L-ASMA and 88 ± 1 % for rac-ASMA. The renal excretion characteristics of (99m)Tc(CO)3(D-ASMA) in humans are superior to those of the other two (99m)Tc(CO)3(ASMA) isomers studied, but are still inferior to (131)I-OIH, even though there was no difference in the clearance of two of (99m)Tc(CO)3(ASMA) isomers and (131)I-OIH in rats. The work described here demonstrates the sensitivity in in vivo biological behavior of (99m)Tc(CO)3(ASMA) isomers to their subtle structural differences.

Association of Serum Triglyceride Level and Gemfibrozil Consumption With Periodontal Status.

PubMed

Sayar, Ferena; Akhondi, Nasrin; Fallah, Soltanali; Moalemnia, Amir Abbas; Cheraghi, Azra

2017-05-01

Hyperlipidemia is a major risk factor for cardiovascular diseases. Considering the suggested association between periodontal and cardiovascular diseases, this study sought to assess the association, if any, between serum triglyceride (TG) levels and gemfibrozil consumption with periodontal parameters. This cross-sectional study was conducted on 90 participants, including 30 individuals with a normal lipid profile (group H), 30 patients with hypertriglyceridemia and not on medication (group N), and 30 patients with hypertriglyceridemia and taking gemfibrozil over a 3-month period (group M). Periodontal parameters including probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index were measured at four sites of each tooth. Serum levels of total cholesterol (TC), TG, low-density lipoprotein, and high-density lipoprotein were measured. Mean values for PD and CAL in the two hypertriglyceridemic groups were significantly higher than those of the H group (P <0.001). After controlling for confounding variables, significant linear correlations were noted between PD and BOP, PD and TC, PD and TG, and CAL and TG in each group (P <0.01). Patients with hypertriglyceridemia had worse periodontal status than healthy controls. Patients with hypertriglyceridemia who were taking gemfibrozil did not show significant differences in CAL and PD compared with untreated patients with hypertriglyceridemia.

Impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

PubMed Central

Chen, Zhe (Jay); Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

2011-01-01

Previous studies have shown that the procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations depends strongly on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al. (Int. J. Radiat. Oncol. Biol. Phys. 41, 1069–1077–1998) was used to characterize the edema evolutions observed previously during clinical PIB for prostate cancer. The concept of biologically effective dose (BED), taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not taken into account appropriately, can increase the cell survival and decrease the probability of local control of PIB. The edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life for radioactive decay and decreasing energy of the photons energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days) is longer than that of 131Cs (9.7 days), because the advantage of the longer 103Pd decay half-life was negated by the lower effective energy of the photons it emits (~21 keV compared to ~30.4 keV for 131Cs). In addition, the impact of edema could be reduced or enhanced by differences in the tumor characteristics (e.g. potential tumor doubling time or the α/β ratio), and the effect of these factors varied for the different radioactive sources. There is a clear need to consider the effects of prostate edema during the planning and evaluation of permanent interstitial brachytherapy treatments for prostate cancer. PMID:21772076

The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

NASA Astrophysics Data System (ADS)

(Jay Chen, Zhe; Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

2011-08-01

Previous studies have shown that procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations strongly depends on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al (1998 Int. J. Radiat. Oncol. Biol. Phys. 41 1069-77) was used to characterize the edema evolutions previously observed during clinical PIB for prostate cancer. The concept of biologically effective dose, taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not appropriately taken into account, can increase the cell survival and decrease the probability of local control of PIB. The magnitude of an edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life of radioactive decay and decreasing photon energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days) is longer than that of 131Cs (9.7 days), because the advantage of the longer 103Pd decay half-life was negated by the lower effective energy of the photons it emits (~21 keV compared to ~30.4 keV for 131Cs). In addition, the impact of edema could be reduced or enhanced by differences in the tumor characteristics (e.g. potential tumor doubling time or the α/β ratio), and the effect of these factors varied for the different radioactive sources. There is a clear need to consider the effects of prostate edema during the planning and evaluation of permanent interstitial brachytherapy treatments for prostate cancer.

Production of novel diagnostic radionuclides in small medical cyclotrons.

PubMed

Synowiecki, Mateusz Adam; Perk, Lars Rutger; Nijsen, J Frank W

2018-01-01

The global network of cyclotrons has expanded rapidly over the last decade. The bulk of its industrial potential is composed of small medical cyclotrons with a proton energy below 20 MeV for radionuclides production. This review focuses on the recent developments of novel medical radionuclides produced by cyclotrons in the energy range of 3 MeV to 20 MeV. The production of the following medical radionuclides will be described based on available literature sources: Tc-99 m, I-123, I-124, Zr-89, Cu-64, Ga-67, Ga-68, In-111, Y-86 and Sc-44. Remarkable developments in the production process have been observed in only some cases. More research is needed to make novel radionuclide cyclotron production available for the medical industry.

Fatigue among short- and long-term thyroid cancer survivors: results from the population-based PROFILES registry.

PubMed

Husson, Olga; Nieuwlaat, Willy-Anne; Oranje, Wilma A; Haak, Harm R; van de Poll-Franse, Lonneke V; Mols, Floortje

2013-10-01

The aims of this study were (i) to obtain insight into the prevalence of fatigue among short- and long-term thyroid cancer (TC) survivors, by comparing a sample of TC survivors with an age- and sex-matched normative population, and (ii) to investigate which demographic, clinical, and TC-specific health-related quality of life (HRQoL) characteristics were associated with fatigue. All patients found to have TC between 1990 and 2008, as registered in the Eindhoven Cancer Registry, received a cross-sectional survey on fatigue (Fatigue Assessment Scale), TC-specific HRQoL (THYCA-QoL), and psychological distress (Hospital Anxiety and Depression Scale). The fatigue scores were compared with those of an age- and sex-matched normative population (n=530). Multiple logistic regression analyses were conducted to investigate the independent associations between clinical and demographic characteristics, TC-specific HRQoL, and psychological distress with fatigue. Eighty-six percent (n=306) responded. TC survivors were more often classified as fatigued or very fatigued (short-term <5 years: 43%; long-term 5-10 years: 44%; long-term 10-15 years: 47%; long-term >15 years: 39%) compared to the normative population (25%; p<0.001). Anxiety (odds ratio (OR) 1.15, 95% confidence interval [CI] 1.03-1.28) and depression (OR 1.43 [CI 1.22-1.68]) were associated with fatigue, as was also the case for TC-specific neuromuscular (OR 1.03 [CI 1.01-1.06]), concentration (OR 1.03 [CI 1.01-1.06]), and psychological TC-specific HRQoL (OR 1.06 [CI 1.02-1.10]). Short- and long-term TC survivors report higher levels of fatigue than an age- and sex-matched normative population do. Both TC-specific HRQoL and psychological distress were associated with fatigue.

Programmed Death Cell Ligand 1 (PD-L1) Is Associated With Survival in Stage I Non-Small Cell Lung Cancer.

PubMed

Sepesi, Boris; Cuentas, Edwin Parra; Canales, Jaime Rodriguez; Behrens, Carmen; Correa, Arlene M; Vaporciyan, Ara; Weissferdt, Annikka; Kalhor, Neda; Moran, Cesar; Swisher, Stephen; Wistuba, Ignacio

2017-01-01

Programmed cell death ligand (PD-L1) has been studied as a predictive immunotherapy biomarker. We investigated PD-L1 expression in the whole tumor and in tumor-infiltrating macrophages (TIMs) as a prognostic biomarker in surgically resected pathologic stage I non-small cell lung cancer. Pathologic specimen from 113 patients with stage I lung cancer (pT1-2a, N0, M0, tumor size 1-5 cm, 79 adenocarcinoma, 34 squamous cell carcinoma) were analyzed for PD-L1 expression in the tumor and in the TIMs using immunohistochemistry and image analysis. Statistics included recursive partitioning, univariable, multivariable, and Kaplan-Meier analyses. Patients whose tumors expressed <4.7% PD-L1 (N = 87) experienced significantly better overall survival (OS) (P = 0.001) than patients with PD-L1 >4.7% (N = 26). Patients with PD-L1 expression in macrophages <6.3% (N = 24) also experienced significantly better (P = 0.005) OS than patients with >6.3% (N = 89). The best outcomes were observed in patients with low PD-L1 expression in both tumor and macrophages with 5-year OS of 94% (N = 17). Contrarily, patients with high PD-L1 expression in both tumor and macrophages experienced 5-year OS of 20% (N = 19). Low PD-L1 expression in the tumor and in the TIMs was independently associated with survival in multivariable analysis (P = 0.000 and P = 0.030, respectively). Lower PD-L1 % expression in the tumor and in the TIMs seems to be associated with significantly better OS in surgically resected stage I lung cancer. Additional studies are needed to validate PD-L1 as a prognostic biomarker in lung cancer and to study the mechanisms of intratumoral immune response. Copyright © 2017 Elsevier Inc. All rights reserved.

Intraoperative Localisation of Impalpable Breast Lesions Utilising the ROLLIS Technique Following Peritumoral ^99mTc-colloid Sentinel Node Lymphoscintigraphy.

PubMed

Hung, Te-Jui; Burrage, John; Bourke, Anita; Taylor, Donna

2017-08-24

Ultrasound or stereotactic guided hook-wire localisation has been the standard-of-care for the pre-surgical localisation of impalpable breast lesions, which account for approximately a third of all breast cancer. Radioguided occult lesion localisation using I-125 seeds (ROLLIS) is a relatively new technique for guiding surgical excision of impalpable breast lesions, and is a promising alternative to the traditional hook-wire method. When combined with Tc-99m labelled colloid for sentinel node mapping in clinically indicated cases, there has been uncertainty regarding whether the downscatter of Tc-99m into the I-125 energy spectrum could adversely affect the intra-operative detection of the I-125 seed, especially pertaining to a peritumoral injection. To evaluate the percentage contribution of downscattered activity from Tc-99m into the I-125 energy spectrum in simulated intra-operative resections of an I-125 seed following different sentinel node injection techniques. Two scenarios were simulated using breast phantoms with lean chicken breast. The first scenario, with a 2cm distance between the Tc-99m injection site and the I-125 seed, simulated a periareolar ipsiquadrant injection with the subdermal or intradermal technique. The second scenario simulated a peritumoral injection technique with the Tc-99m bolus and an I-125 seed at the same site. Count rates were acquired with a hand-held gamma probe, and the percentage contribution of downscattered Tc-99m gamma photons to the I-125 energy window was calculated. In scenarios one and two, downscattered Tc-99m activity contributed 0.5% and 33% respectively to the detected count rate in the I-125 energy window. In both scenarios, the I-125 seed was successfully localised and removed using the gamma probe. There is no significant contribution of downscattered activity associated with a peritumoral injection of Tc-99m to adversely affect the accurate intra-operative localisation of an I- 125 seed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

SU-F-19A-05: Experimental and Monte Carlo Characterization of the 1 Cm CivaString 103Pd Brachytherapy Source

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

Reed, J; Micka, J; Culberson, W

Purpose: To determine the in-air azimuthal anisotropy and in-water dose distribution for the 1 cm length of the CivaString {sup 103}Pd brachytherapy source through measurements and Monte Carlo (MC) simulations. American Association of Physicists in Medicine Task Group No. 43 (TG-43) dosimetry parameters were also determined for this source. Methods: The in-air azimuthal anisotropy of the source was measured with a NaI scintillation detector and simulated with the MCNP5 radiation transport code. Measured and simulated results were normalized to their respective mean values and compared. The TG-43 dose-rate constant, line-source radial dose function, and 2D anisotropy function for this sourcemore » were determined from LiF:Mg,Ti thermoluminescent dosimeter (TLD) measurements and MC simulations. The impact of {sup 103}Pd well-loading variability on the in-water dose distribution was investigated using MC simulations by comparing the dose distribution for a source model with four wells of equal strength to that for a source model with strengths increased by 1% for two of the four wells. Results: NaI scintillation detector measurements and MC simulations of the in-air azimuthal anisotropy showed that ≥95% of the normalized data were within 1.2% of the mean value. TLD measurements and MC simulations of the TG-43 dose-rate constant, line-source radial dose function, and 2D anisotropy function agreed to within the experimental TLD uncertainties (k=2). MC simulations showed that a 1% variability in {sup 103}Pd well-loading resulted in changes of <0.1%, <0.1%, and <0.3% in the TG-43 dose-rate constant, radial dose distribution, and polar dose distribution, respectively. Conclusion: The CivaString source has a high degree of azimuthal symmetry as indicated by the NaI scintillation detector measurements and MC simulations of the in-air azimuthal anisotropy. TG-43 dosimetry parameters for this source were determined from TLD measurements and MC simulations. {sup 103}Pd well-loading variability results in minimal variations in the in-water dose distribution according to MC simulations. This work was partially supported by CivaTech Oncology, Inc. through an educational grant for Joshua Reed, John Micka, Wesley Culberson, and Larry DeWerd and through research support for Mark Rivard.« less

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

Wang, Yazhen; Musser, Sarah K.; Saleh, Sam

1,N{sup 2}-Propanodeoxyguanosine (PdG) is a stable structural analogue for the 3-(2'-deoxy-{beta}-d-erythro-pentofuranosyl)pyrimido[1,2-?]purin-10(3H)-one (M{sub 1}dG) adduct derived from exposure of DNA to base propenals and to malondialdehyde. The structures of ternary polymerase-DNA-dNTP complexes for three template-primer DNA sequences were determined, with the Y-family Sulfolobus solfataricus DNA polymerase IV (Dpo4), at resolutions between 2.4 and 2.7 {angstrom}. Three template 18-mer-primer 13-mer sequences, 5'-d(TCACXAAATCCTTCCCCC)-3'{center_dot}5'-d(GGGGGAAGGATTT)-3' (template I), 5'-d(TCACXGAATCCTTCCCCC)-3'{center_dot}5'-d(GGGGGAAGGATTC)-3' (template II), and 5'-d(TCATXGAATCCTTCCCCC)-3'{center_dot}5'-d(GGGGGAAGGATTC)-3' (template III), where X is PdG, were analyzed. With templates I and II, diffracting ternary complexes including dGTP were obtained. The dGTP did not pair with PdG, but instead with the 5'-neighboring templatemore » dC, utilizing Watson-Crick geometry. Replication bypass experiments with the template-primer 5?-TCACXAAATCCTTACGAGCATCGCCCCC-3'{center_dot}5'-GGGGGCGATGCTCGTAAGGATTT-3', where X is PdG, which includes PdG in the 5'-CXA-3' template sequence as in template I, showed that the Dpo4 polymerase inserted dGTP and dATP when challenged by the PdG adduct. For template III, in which the template sequence was 5'-TXG-3', a diffracting ternary complex including dATP was obtained. The dATP did not pair with PdG, but instead with the 5'-neighboring T, utilizing Watson-Crick geometry. Thus, all three ternary complexes were of the 'type II' structure described for ternary complexes with native DNA [Ling, H., Boudsocq, F., Woodgate, R., and Yang, W. (2001) Cell 107, 91--102]. The PdG adduct remained in the anti conformation about the glycosyl bond in each of these threee ternary complexes. These results provide insight into how -1 frameshift mutations might be generated for the PdG adduct, a structural model for the exocylic M{sub 1}dG adduct formed by malondialdehyde.« less

Superconductivity with extremely large upper critical fields in Nb2Pd0.81S5

PubMed Central

Zhang, Q.; Li, G.; Rhodes, D.; Kiswandhi, A.; Besara, T.; Zeng, B.; Sun, J.; Siegrist, T.; Johannes, M. D.; Balicas, L.

2013-01-01

Here, we report the discovery of superconductivity in a new transition metal-chalcogenide compound, i.e. Nb2Pd0.81S5, with a transition temperature Tc ≅ 6.6 K. Despite its relatively low Tc, it displays remarkably high and anisotropic superconducting upper critical fields, e.g. μ0Hc2 (T → 0 K) > 37 T for fields applied along the crystallographic b-axis. For a field applied perpendicularly to the b-axis, μ0Hc2 shows a linear dependence in temperature which coupled to a temperature-dependent anisotropy of the upper critical fields, suggests that Nb2Pd0.81S5 is a multi-band superconductor. This is consistent with band structure calculations which reveal nearly cylindrical and quasi-one-dimensional Fermi surface sheets having hole and electron character, respectively. The static spin susceptibility as calculated through the random phase approximation, reveals strong peaks suggesting proximity to a magnetic state and therefore the possibility of unconventional superconductivity. PMID:23486091

Development of medicine-intended isotope production technologies at Yerevan Physics Institute

NASA Astrophysics Data System (ADS)

Avetisyan, Albert; Avagyan, Robert; Kerobyan, Ivetta; Dallakyan, Ruben; Harutyunyan, Gevorg; Melkonyan, Aleksandr

2015-05-01

Accelerator-based 99mTc and 123I isotopes production technologies were created and developed at A.Alikhanyan National Science Laboratory (former Yerevan Physics Institute - YerPhI). The method involves the irradiation of natural molybdenum (for 99mTc production) and natural xenon (for 123I production) using high-intensity bremsstrahlung photons from the electron beam of the LUE50 linear electron accelerator located at the YerPhI. We have developed and tested the extraction of 99mTc and 123I from the irradiated natural MoO3 and natural Xe, respectively. The production method has been developed and shown to be successful. The current activity is devoted to creation and development of the technology of direct production 99mTc on the 100Mo as target materials using the proton beam from an IBA C18/18 cyclotron. The proton cyclotron C18/18 (producer - IBA, Belgium) was purchased and will be installed nearby AANL (YerPhI) till end 2014. The 18 MeV protons will be used to investigate accelerator-based schemes for the direct production of 99mTc. Main topics of studies will include experimental measurement of 99mTc production yield for different energies of protons, irradiation times, intensities, development of new methods of 99mTc extraction from irradiated materials, development of target preparation technology, development of target material recovery methods for multiple use and others.

Photodemethylation of Methylmercury in Eastern Canadian Arctic Thaw Pond and Lake Ecosystems.

PubMed

Girard, Catherine; Leclerc, Maxime; Amyot, Marc

2016-04-05

Permafrost thaw ponds of the warming Eastern Canadian Arctic are major landscape constituents and often display high levels of methylmercury (MeHg). We examined photodegradation potentials in high-dissolved organic matter (DOC) thaw ponds on Bylot Island (BYL) and a low-DOC oligotrophic lake on Cornwallis Island (Char Lake). In BYL, the ambient MeHg photodemethylation (PD) rate over 48 h of solar exposure was 6.1 × 10(-3) m(2) E(-1), and the rate in MeHg amended samples was 9.3 × 10(-3) m(2) E(-1). In contrast, in low-DOC Char Lake, PD was only observed in the first 12 h, which suggests that PD may not be an important loss process in polar desert lakes. Thioglycolic acid addition slowed PD, while glutathione and chlorides did not impact northern PD rates. During an ecosystem-wide experiment conducted in a covered BYL pond, there was neither net MeHg increase in the dark nor loss attributable to PD following re-exposure to sunlight. We propose that high-DOC Arctic thaw ponds are more prone to MeHg PD than nearby oligotrophic lakes, likely through photoproduction of reactive species rather than via thiol complexation. However, at the ecosystem level, these ponds, which are widespread through the Arctic, remain likely sources of MeHg for neighboring systems.

Kinetics and inhibition of cyclomaltodextrinase from alkalophilic Bacillus sp. I-5.

PubMed

Kim, M J; Park, W S; Lee, H S; Kim, T J; Shin, J H; Yoo, S H; Cheong, T K; Ryu, S; Kim, J C; Kim, J W; Moon, T W; Robyt, J F; Park, K H

2000-01-01

The cyclomaltodextrinase from alkalophilic Bacillus sp. I-5 (CDase I-5) was expressed in Escherichia coli and the purified enzyme was used for characterization of the enzyme action. The hydrolysis products were monitored by both HPLC and high-performance ion chromatography analysis that enable the kinetic analysis of the cyclomaltodextrin (CD)-degrading reaction. Analysis of the kinetics of cyclomaltodextrin hydrolysis by CDase I-5 indicated that ring-opening of the cyclomaltodextrin was the major limiting step and that CDase I-5 preferentially degraded the linear maltodextrin chain by removing the maltose unit. The substrate binding affinity of the enzyme was almost same for those of cyclomaltodextrins while the rate of ring-opening was the fastest for cyclomaltoheptaose. Acarbose and methyl 6-amino-6-deoxy-alpha-d-glucopyranoside were relatively strong competitive inhibitors with K(i) values of 1.24 x 10(-3) and 8.44 x 10(-1) mM, respectively. Both inhibitors are likely to inhibit the ring-opening step of the CD degradation reaction. Copyright 2000 Academic Press.

Synthesis, Characterization, and Preclinical Evaluation of (99m)Tc-Labeled Macrobicyclic and Tricyclic Chelators as Single Photon Emission Computed Tomography Tracer.

PubMed

Yadav, Neelam; Chuttani, Krishna; Mishra, Anil K; Singh, Bachcha

2016-05-01

The novel tetraaza macrobicyclic chelator 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-2,10-dione (TBPD) and pentaaza macrotricyclic chelator 9-oxa-3,6,12,15,21-pentaazatricyclo[15,3,2,1]trieicos-1(21),17,19-triene-2,7,11,16-tetradione (OPTT) were synthesized, characterized, and radiolabeled with (99m)Tc to produce (99m)Tc-TBPD and (99m)Tc-OPTT. These radiolabeled complexes were prepared with high radiolabeling yield, radiochemical purity, and good in vitro stability up to 24 h. The labeling efficiency of (99m)Tc-TBPD and (99m)Tc-OPTT was found 98% and 97%. In vitro serum stability of (99m)Tc-TBPD was found to be 95.2%, while that of (99m)Tc-OPTT 94.2% up to 24 h. Blood kinetics experiments of (99m)Tc-labeled complexes showed biphasic pattern of blood clearance. About 99.57 ± 0.89% activity of (99m)Tc-TBPD and 99.42 ± 0.88% activity of (9m)Tc-OPTT were cleared off blood stream at 24 h postadministration. The biological half-life of (99m) Tc-TBPD was observed: t1/2(F) 1 h 5 min and t1/2(S) 12 h and biological half-life of (99m)Tc-OPTT was observed: t1/2(F) 1 h 10 min and t1/2(S) 9 h 50 min, respectively. The biodistribution studies revealed that maximum uptake of (99m)Tc-TBPD was found in liver, concluded that excretory pathway is hepatobiliary, while that of (99m)Tc-OPTT was renal as well as hepatobiliary. The negligible activity observed in stomach confirming the stability of radiolabeled complex in biological milieu. In vitro cytotoxicity study of TBPD and OPTT did not show any considerable antiproliferative activity against cancer cells of human cervical SW756, HeLa, and glioblastoma U-87, U373 cell lines. © 2015 John Wiley & Sons A/S.

Weight History, All-Cause and Cause-Specific Mortality in Three Prospective Cohort Studies

PubMed Central

Yu, Edward; Stokes, Andrew C.; Ley, Sylvia H.; Manson, JoAnn E.; Willett, Walter; Satija, Ambika; Hu, Frank B.

2017-01-01

BACKGROUND The relationship between body mass index (BMI) and mortality remains controversial. OBJECTIVE To investigate the relationship between maximum BMI over 16 years and subsequent mortality. DESIGN Three prospective cohort studies. SETTING Nurses’ Health Study I and II, Health Professionals Follow-up Study. PARTICIPANTS 225,072 men and women accruing 32,571 deaths over a mean of 12.3 years of follow-up. MEASUREMENTS Maximum BMI over 16 years of weight history and all-cause and cause-specific mortality. RESULTS Maximum BMIs in the overweight (25.0 to 29.9 kg/m2) (multivariate hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.03 – 1.08), obese I (30.0 to 34.9 kg/m2), (HR, 1.24; 95% CI, 1.20 – 1.29), and obese II (≥ 35.0 kg/m2) (HR, 1.73; 95% CI, 1.66 – 1.80) categories were associated with increases in risk of all-cause mortality. The pattern of excess risk with a maximum BMI above normal weight was maintained across strata defined by smoking status, sex, and age, but the excess was greatest among those <70 years old and never smokers. In contrast, a significant inverse association between overweight and mortality (HR, 0.96; 95% CI, 0.94 – 0.99) was observed when BMI was defined using a single baseline measurement. Maximum overweight was also associated with increased cause-specific mortality, including deaths from cardiovascular diseases and coronary heart disease. LIMITATIONS Residual confounding and misclassification. CONCLUSIONS The paradoxical association between overweight and mortality is reversed in analyses incorporating weight history. Maximum BMI may be a useful metric to minimize reverse causation bias associated with a single baseline BMI assessment. PMID:28384755

Evaluating 99mTc Auger electrons for targeted tumor radiotherapy by computational methods.

PubMed

Tavares, Adriana Alexandre S; Tavares, João Manuel R S

2010-07-01

Technetium-99m (99mTc) has been widely used as an imaging agent but only recently has been considered for therapeutic applications. This study aims to analyze the potential use of 99mTc Auger electrons for targeted tumor radiotherapy by evaluating the DNA damage and its probability of correct repair and by studying the cellular kinetics, following 99mTc Auger electron irradiation in comparison to iodine-131 (131I) beta minus particles and astatine-211 (211At) alpha particle irradiation. Computational models were used to estimate the yield of DNA damage (fast Monte Carlo damage algorithm), the probability of correct repair (Monte Carlo excision repair algorithm), and cell kinetic effects (virtual cell radiobiology algorithm) after irradiation with the selected particles. The results obtained with the algorithms used suggested that 99mTc CKMMX (all M-shell Coster-Kroning--CK--and super-CK transitions) electrons and Auger MXY (all M-shell Auger transitions) have a therapeutic potential comparable to high linear energy transfer 211At alpha particles and higher than 131I beta minus particles. All the other 99mTc electrons had a therapeutic potential similar to 131I beta minus particles. 99mTc CKMMX electrons and Auger MXY presented a higher probability to induce apoptosis than 131I beta minus particles and a probability similar to 211At alpha particles. Based on the results here, 99mTc CKMMX electrons and Auger MXY are useful electrons for targeted tumor radiotherapy.

Exploring the Potential of (99m)Tc(CO)3-Labeled Triazolyl Peptides for Tumor Diagnosis.

PubMed

Gaonkar, Raghuvir H; Ganguly, Soumya; Baishya, Rinku; Dewanjee, Saikat; Sinha, Samarendu; Gupta, Amit; Ganguly, Shantanu; Debnath, Mita C

2016-04-01

In recent years the authors have reported on (99m)Tc(CO)3-labeled peptides that serve as carriers for biomolecules or radiopharmaceuticals to the tumors. In continuation of that work they report the synthesis of a pentapeptide (Met-Phe-Phe-Gly-His; pep-1), a hexapeptide (Met-Phe-Phe-Asp-Gly-His; pep-2), and a tetrapeptide (Asp-Gly-Arg-His; pep-3) and the attachment of 3-amino-1,2,4-triazole to the β carboxylic function of the aspartic acid unit of pep-2 and pep-3. The pharmacophores were radiolabeled in high yields with [(99m)Tc(CO)3(H2O)3](+) metal aqua ion, characterized for their stability in serum and saline, as well as in His solution, and found to be substantially stable. B16F10 cell line binding studies showed favorable uptake and internalization. In vivo behavior of the radiolabeled triazolyl peptides was assessed in mice bearing induced tumor. The (99m)Tc(CO)3-triazolyl pep-3 demonstrated rapid urinary clearance and comparatively better tumor uptake. Imaging studies showed visualization of the tumor using (99m)Tc(CO)3-triazolyl pep-3, but due to high abdominal background, low delineation occurred. Based on the results further experiments will be carried out for targeting tumor with triazolyl peptides.

Spectroscopic Properties of Tc(I) Tricarbonyl Species Relevant to the Hanford Tank Waste

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

Levitskaia, Tatiana G.; Andersen, Amity; Chatterjee, Sayandev

2015-12-04

Technetium-99 (Tc) exists predominately in soluble forms in the liquid supernatant and salt cake fractions of the nuclear tank waste stored at the U.S. DOE Hanford Site. In the strongly alkaline environments prevalent in the tank waste, its dominant chemical form is pertechnetate (TcO4-, oxidation state +7). However, attempts to remove Tc from the Hanford tank waste using ion-exchange processes specific to TcO 4 - only met with limited success, particularly processing tank waste samples containing elevated concentrations of organic complexants. This suggests that a significant fraction of the soluble Tc can be present as non-pertechnetate low-valent Tc (oxidation statemore » < +7) (non-pertechnetate). The chemical identities of these non-pertechnetate species are poorly understood. Previous analysis of the SY-101 and SY-103 tank waste samples provided strong evidence that non-pertechnetate can be comprised of [Tc(CO) 3] + complexes containing Tc in oxidation state +1 (Lukens et al. 2004). During the last two years, our team has expanded this work and demonstrated that high-ionic-strength solutions typifying tank waste supernatants promote oxidative stability of the [Tc(CO) 3] + species (Rapko et al. 2013; Levitskaia et al. 2014). It also was observed that high-ionic-strength alkaline matrices stabilize Tc(VI) and potentially Tc(IV) oxidation states, particularly in presence organic chelators, suggesting that the relevant Tc compounds can serve as important redox intermediates facilitating the reduction of Tc(VII) to Tc(I). Designing strategies for effective Tc processing, including separation and immobilization, necessitates understanding the molecular structure of these non-pertechnetate species and their identification in the actual tank waste samples. To-date, only limited information exists regarding the nature and characterization of the Tc(I), Tc(IV), and Tc(VI) species. One objective of this project is to identify the form of non-pertechnetate in the Hanford waste. To do this, we are developing a spectral library of reference non-pertechnetate compounds that can be compared against actual waste samples. The emphasis of the fiscal year 2015 work was Tc(I) tricarbonyl [Tc(CO) 3] + compounds. The key findings are summarized below.« less

Monte Carlo based approach to the LS-NaI 4πβ-γ anticoincidence extrapolation and uncertainty

PubMed Central

Fitzgerald, R.

2016-01-01

The 4πβ-γ anticoincidence method is used for the primary standardization of β−, β+, electron capture (EC), α, and mixed-mode radionuclides. Efficiency extrapolation using one or more γ ray coincidence gates is typically carried out by a low-order polynomial fit. The approach presented here is to use a Geant4-based Monte Carlo simulation of the detector system to analyze the efficiency extrapolation. New code was developed to account for detector resolution, direct γ ray interaction with the PMT, and implementation of experimental β-decay shape factors. The simulation was tuned to 57Co and 60Co data, then tested with 99mTc data, and used in measurements of 18F, 129I, and 124I. The analysis method described here offers a more realistic activity value and uncertainty than those indicated from a least-squares fit alone. PMID:27358944

CD103+CD8+ T lymphocytes in non-small cell lung cancer are phenotypically and functionally primed to respond to PD-1 blockade.

PubMed

Wang, Peiliang; Huang, Bing; Gao, Yi; Yang, Jianjian; Liang, Zhihui; Zhang, Ni; Fu, Xiangning; Li, Lequn

2018-03-01

CD103 + CD8 + tumor infiltrating lymphocytes (TILs) have been linked to prolonged survival in various types of cancer including non-small cell lung cancer (NSCLC). However, the factors associated with the retention of CD103 + CD8 + TILs in lung cancer tissues remain largely unknown. Additionally, the contribution of CD103 + CD8 + TILs to effective PD-1 based immunotherapy has not been fully elucidated. In this study, we identified that the expression levels of E-cadherin and TGF-β were significantly correlated with the distribution and the density of CD103 + TILs in lung cancer tumor tissues. Unexpectedly, we observed that CD103 + CD8 + TILs that expressed higher levels of PD-1 co-express Ki-67. Moreover, CD103 + CD8 + TILs expressed an increased level of T-bet compared to their counterparts, indicating these cells may be better armed for immunotherapy. Lastly, PD-1 pathway blockade led to a significantly increased production of IFN-γ by CD103 + CD8 + TILs, suggesting CD103 + CD8 + TILs could serve as a predictive biomarker for PD-1 based immunotherapy. Copyright © 2018 Elsevier Inc. All rights reserved.

SU-F-19A-06: Experimental Investigation of the Energy Dependence of TLD Sensitivity in Low-Energy Photon Beams

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

Chen, Z; Nath, R

Purpose: To measure the energy dependence of TLD sensitivity in lowenergy photon beams with equivalent mono-energetic energy matching those of 103Pd, 125I and 131Cs brachytherapy sources. Methods: A Pantek DXT 300 x-ray unit (Precision X-ray, Branford, CT), with stable digital voltage control down to 20 kV, was used to establish three lowenergy photon beams with narrow energy spread and equivalent monoenergetic energies matching those of 103Pd, 125I and 131Cs brachytherapy sources. The low-energy x-ray beams and a reference 6 MV photon beam were calibrated according to the AAPM TG-61 and TG-51 protocols, respectively, using a parallel-plate low-energy chamber and amore » Farmer cylindrical chamber with NIST traceable calibration factors. The dose response of model TLD-100 micro-cubes (1×1×1 mm{sup 3}) in each beam was measured for five different batches of TLDs (each contained approximately 100 TLDs) that have different histories of irradiation and usage. Relative absorbed dose sensitivity was determined as the quotient of the slope of dose response for a beam-of-interest to that of the reference beam. Results: Equivalent mono-energetic photon energies of the low-energy beams established for 103Pd, 125I and 131Cs sources were 20.5, 27.5, and 30.1 keV, respectively. Each beam exhibited narrow spectral spread with energyhomogeneity index close to 90%. The relative absorbed-dose sensitivity was found to vary between different batches of TLD with maximum differences of up to 8%. The mean and standard deviation determined from the five TLD batches was 1.453 ± 0.026, 1.541 ± 0.035 and 1.529 ± 0.051 for the simulated 103P, 125I and 131Cs beams, respectively. Conclusion: Our measured relative absorbed-dose sensitivities are greater than the historically measured value of 1.41. We find that the relative absorbed-dose sensitivity of TLD in the 103P beam is approximately 5% lower than that of 125I and 131Cs beams. Comparison of our results with other studies will be presented.« less

Superconductivity in ThPd2Ge2

NASA Astrophysics Data System (ADS)

Domieracki, Krzysztof; Wiśniewski, Piotr; Wochowski, Konrad; Romanova, Tetiana; Hackemer, Alicja; Gorzelniak, Roman; Pikul, Adam; Kaczorowski, Dariusz

2018-05-01

Our on-going search for unconventional superconductors among the ThTE2Ge2 phases (TE is a d-electron transition metal) revealed that ThPd2Ge2, which crystallizes with a body-centered tetragonal ThCr2Si2-type structure, exhibits superconductivity at low temperatures. In this paper, we report on the electrical transport and thermodynamic properties of a polycrystalline sample of this new superconductor, extended down to 50 mK. The experimental data indicates weakly-coupled type-II superconductivity with Tc = 0.63(2) K and μ0Hc2(0) = 32(2) mT.

Ambient Air Pollution Exposures and Risk of Parkinson Disease

PubMed Central

Liu, Rui; Young, Michael T.; Chen, Jiu-Chiuan; Kaufman, Joel D.; Chen, Honglei

2016-01-01

Background: Few epidemiologic studies have evaluated the effects of air pollution on the risk of Parkinson disease (PD). Objective: We investigated the associations of long-term residential concentrations of ambient particulate matter (PM) < 10 μm in diameter (PM10) and < 2.5 μm in diameter (PM2.5) and nitrogen dioxide (NO2) in relation to PD risk. Methods: Our nested case–control analysis included 1,556 self-reported physician-diagnosed PD cases identified between 1995 and 2006 and 3,313 controls frequency-matched on age, sex, and race. We geocoded home addresses reported in 1995–1996 and estimated the average ambient concentrations of PM10, PM2.5, and NO2 using a national fine-scale geostatistical model incorporating roadway information and other geographic covariates. Air pollutant exposures were analyzed as both quintiles and continuous variables, adjusting for matching variables and potential confounders. Results: We observed no statistically significant overall association between PM or NO2 exposures and PD risk. However, in preplanned subgroup analyses, a higher risk of PD was associated with higher exposure to PM10 (ORQ5 vs. Q1 = 1.65; 95% CI: 1.11, 2.45; p-trend = 0.02) among women, and with higher exposure to PM2.5 (ORQ5 vs. Q1 = 1.29; 95% CI: 0.94, 1.76; p-trend = 0.04) among never smokers. In post hoc analyses among female never smokers, both PM2.5 (ORQ5 vs. Q1 = 1.79; 95% CI: 1.01, 3.17; p-trend = 0.05) and PM10 (ORQ5 vs. Q1 = 2.34; 95% CI: 1.29, 4.26; p-trend = 0.01) showed positive associations with PD risk. Analyses based on continuous exposure variables generally showed similar but nonsignificant associations. Conclusions: Overall, we found limited evidence for an association between exposures to ambient PM10, PM2.5, or NO2 and PD risk. The suggestive evidence that exposures to PM2.5 and PM10 may increase PD risk among female never smokers warrants further investigation. Citation: Liu R, Young MT, Chen JC, Kaufman JD, Chen H. 2016. Ambient air pollution exposures and risk of Parkinson disease. Environ Health Perspect 124:1759–1765; http://dx.doi.org/10.1289/EHP135 PMID:27285422

Ambient Air Pollution Exposures and Risk of Parkinson Disease.

PubMed

Liu, Rui; Young, Michael T; Chen, Jiu-Chiuan; Kaufman, Joel D; Chen, Honglei

2016-11-01

Few epidemiologic studies have evaluated the effects of air pollution on the risk of Parkinson disease (PD). We investigated the associations of long-term residential concentrations of ambient particulate matter (PM) < 10 μm in diameter (PM10) and < 2.5 μm in diameter (PM2.5) and nitrogen dioxide (NO2) in relation to PD risk. Our nested case-control analysis included 1,556 self-reported physician-diagnosed PD cases identified between 1995 and 2006 and 3,313 controls frequency-matched on age, sex, and race. We geocoded home addresses reported in 1995-1996 and estimated the average ambient concentrations of PM10, PM2.5, and NO2 using a national fine-scale geostatistical model incorporating roadway information and other geographic covariates. Air pollutant exposures were analyzed as both quintiles and continuous variables, adjusting for matching variables and potential confounders. We observed no statistically significant overall association between PM or NO2 exposures and PD risk. However, in preplanned subgroup analyses, a higher risk of PD was associated with higher exposure to PM10 (ORQ5 vs. Q1 = 1.65; 95% CI: 1.11, 2.45; p-trend = 0.02) among women, and with higher exposure to PM2.5 (ORQ5 vs. Q1 = 1.29; 95% CI: 0.94, 1.76; p-trend = 0.04) among never smokers. In post hoc analyses among female never smokers, both PM2.5 (ORQ5 vs. Q1 = 1.79; 95% CI: 1.01, 3.17; p-trend = 0.05) and PM10 (ORQ5 vs. Q1 = 2.34; 95% CI: 1.29, 4.26; p-trend = 0.01) showed positive associations with PD risk. Analyses based on continuous exposure variables generally showed similar but nonsignificant associations. Overall, we found limited evidence for an association between exposures to ambient PM10, PM2.5, or NO2 and PD risk. The suggestive evidence that exposures to PM2.5 and PM10 may increase PD risk among female never smokers warrants further investigation. Citation: Liu R, Young MT, Chen JC, Kaufman JD, Chen H. 2016. Ambient air pollution exposures and risk of Parkinson disease. Environ Health Perspect 124:1759-1765; http://dx.doi.org/10.1289/EHP135.

Geographical Distribution of Trypanosoma cruzi Genotypes in Venezuela

PubMed Central

Carrasco, Hernán J.; Segovia, Maikell; Llewellyn, Martin S.; Morocoima, Antonio; Urdaneta-Morales, Servio; Martínez, Cinda; Martínez, Clara E.; Garcia, Carlos; Rodríguez, Marlenes; Espinosa, Raul; de Noya, Belkisyolé A.; Díaz-Bello, Zoraida; Herrera, Leidi; Fitzpatrick, Sinead; Yeo, Matthew; Miles, Michael A.; Feliciangeli, M. Dora

2012-01-01

Chagas disease is an endemic zoonosis native to the Americas and is caused by the kinetoplastid protozoan parasite Trypanosoma cruzi. The parasite is also highly genetically diverse, with six discrete typing units (DTUs) reported TcI – TcVI. These DTUs broadly correlate with several epidemiogical, ecological and pathological features of Chagas disease. In this manuscript we report the most comprehensive evaluation to date of the genetic diversity of T. cruzi in Venezuela. The dataset includes 778 samples collected and genotyped over the last twelve years from multiple hosts and vectors, including nine wild and domestic mammalian host species, and seven species of triatomine bug, as well as from human sources. Most isolates (732) can be assigned to the TcI clade (94.1%); 24 to the TcIV group (3.1%) and 22 to TcIII (2.8%). Importantly, among the 95 isolates genotyped from human disease cases, 79% belonged to TcI - a DTU common in the Americas, however, 21% belonged to TcIV- a little known genotype previously thought to be rare in humans. Furthermore, were able to assign multiple oral Chagas diseases cases to TcI in the area around the capital, Caracas. We discuss our findings in the context of T. cruzi DTU distributions elsewhere in the Americas, and evaluate the impact they have on the future of Chagas disease control in Venezuela. PMID:22745843

Geographical distribution of Trypanosoma cruzi genotypes in Venezuela.

PubMed

Carrasco, Hernán J; Segovia, Maikell; Llewellyn, Martin S; Morocoima, Antonio; Urdaneta-Morales, Servio; Martínez, Cinda; Martínez, Clara E; Garcia, Carlos; Rodríguez, Marlenes; Espinosa, Raul; de Noya, Belkisyolé A; Díaz-Bello, Zoraida; Herrera, Leidi; Fitzpatrick, Sinead; Yeo, Matthew; Miles, Michael A; Feliciangeli, M Dora

2012-01-01

Chagas disease is an endemic zoonosis native to the Americas and is caused by the kinetoplastid protozoan parasite Trypanosoma cruzi. The parasite is also highly genetically diverse, with six discrete typing units (DTUs) reported TcI - TcVI. These DTUs broadly correlate with several epidemiogical, ecological and pathological features of Chagas disease. In this manuscript we report the most comprehensive evaluation to date of the genetic diversity of T. cruzi in Venezuela. The dataset includes 778 samples collected and genotyped over the last twelve years from multiple hosts and vectors, including nine wild and domestic mammalian host species, and seven species of triatomine bug, as well as from human sources. Most isolates (732) can be assigned to the TcI clade (94.1%); 24 to the TcIV group (3.1%) and 22 to TcIII (2.8%). Importantly, among the 95 isolates genotyped from human disease cases, 79% belonged to TcI - a DTU common in the Americas, however, 21% belonged to TcIV- a little known genotype previously thought to be rare in humans. Furthermore, were able to assign multiple oral Chagas diseases cases to TcI in the area around the capital, Caracas. We discuss our findings in the context of T. cruzi DTU distributions elsewhere in the Americas, and evaluate the impact they have on the future of Chagas disease control in Venezuela.

Evaluation of New Tc-99m-Labeled Arg-X-Asp-Conjugated Alpha-Melanocyte Stimulating Hormone Peptides for Melanoma Imaging

PubMed Central

Flook, Adam M.; Yang, Jianquan; Miao, Yubin

2013-01-01

The purpose of this study was to examine the melanoma targeting and imaging properties of two new 99mTc-labeled Arg-X-Asp-conjugated alpha-melanocyte stimulating hormone (α-MSH) peptides. RTD-Lys-(Arg11)CCMSH {c[Asp-Arg-Thr-Asp-DTyr]-Lys-Cys-Cys-Glu-His-DPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2} and RVD-Lys-(Arg11)CCMSH peptides were synthesized and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution and melanoma imaging properties of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The IC50 values of RTD-Lys-(Arg11)CCMSH and RVD-Lys-(Arg11)CCMSH were 0.7 ± 0.07 and 1.0 ± 0.3 nM in B16/F1 melanoma cells. Both 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH displayed high melanoma uptake. 99mTc-RTD-Lys-(Arg11)CCMSH exhibited the peak tumor uptake of 18.77 ± 5.13% ID/g at 2 h post-injection, whereas 99mTc-RVD-Lys-(Arg11)CCMSH reached the peak tumor uptake of 19.63 ± 4.68% ID/g at 4 h post-injection. Both 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH showed low accumulation in normal organs (<1.7% ID/g) except for the kidneys at 2 h post-injection. The renal uptake of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH was 135.14 ± 23.62 and 94.01 ± 18.31% ID/g at 2 h post-injection, respectively. The melanoma lesions were clearly visualized by SPECT/CT using either 99mTc-RTD-Lys-(Arg11)CCMSH or 99mTc-RVD-Lys-(Arg11)CCMSH as an imaging probe at 2 h post-injection. Overall, the introduction of Thr or Val residue retained high melanoma uptake of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH. However, high renal uptake of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH need to be reduced to facilitate their future applications. PMID:23885640

Evaluation of new Tc-99m-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone peptides for melanoma imaging.

PubMed

Flook, Adam M; Yang, Jianquan; Miao, Yubin

2013-09-03

The purpose of this study was to examine the melanoma targeting and imaging properties of two new (99m)Tc-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RTD-Lys-(Arg(11))CCMSH {c[Asp-Arg-Thr-Asp-DTyr]-Lys-Cys-Cys-Glu-His-DPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2} and RVD-Lys-(Arg(11))CCMSH peptides were synthesized, and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution and melanoma imaging properties of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The IC50 values of RTD-Lys-(Arg(11))CCMSH and RVD-Lys-(Arg(11))CCMSH were 0.7 ± 0.07 and 1.0 ± 0.3 nM in B16/F1 melanoma cells. Both (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH displayed high melanoma uptake. (99m)Tc-RTD-Lys-(Arg(11))CCMSH exhibited the highest tumor uptake of 18.77 ± 5.13% ID/g at 2 h postinjection, whereas (99m)Tc-RVD-Lys-(Arg(11))CCMSH reached the highest tumor uptake of 19.63 ± 4.68% ID/g at 4 h postinjection. Both (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH showed low accumulation in normal organs (<1.7% ID/g) except for the kidneys at 2 h postinjection. The renal uptake of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH was 135.14 ± 23.62 and 94.01 ± 18.31% ID/g at 2 h postinjection, respectively. The melanoma lesions were clearly visualized by single-photon emission computed tomography (SPECT)/CT using either (99m)Tc-RTD-Lys-(Arg(11))CCMSH or (99m)Tc-RVD-Lys-(Arg(11))CCMSH as an imaging probe at 2 h postinjection. Overall, the introduction of Thr or Val residue retained high melanoma uptake of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH. However, high renal uptake of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH need to be reduced to facilitate their future applications.

New multifunctional ligands for potential use in the design therapeutic or diagnostic radiopharmaceutical imaging agents

DOEpatents

Katti, Kattesh V.; Volkert, Wynn A.; Ketring, Alan R.; Singh, Prahlad R.

1997-01-01

A class of diagnostic and therapeutic compounds derived from phosphinimines that include ligands containing either a single phosphinimine functionality or both a phosphinimine group and a phosphine or arsine group, or an aminato group, or a second phosphinimine moiety. These phosphinimine ligands are complexed to early transition metal radionuclides (e.g. .sup.99m Tc or .sup.186 Re/.sup.188 Re) or late transition metals (e.g., .sup.105 Rh or .sup.109 Pd). The complexes with these metals .sup.186 Re/.sup.188 Re, .sup.99m Tc and .sup.109 Pd exhibit a high in vitro and high in vivo stability. The complexes are formed in high yields and can be neutral or charged. These ligands can also be used to form stable compounds with paramagnetic transition metals (e.g. Fe and Mn) for potential use as MRI contrast agents. Applications for the use of ligands and making the ligands are also disclosed.

New multifunctional ligands for potential use in the design therapeutic or diagnostic radiopharmaceutical imaging agents

DOEpatents

Katti, K.V.; Volkert, W.A.; Ketring, A.R.; Singh, P.R.

1997-02-11

A class of diagnostic and therapeutic compounds are derived from phosphinimines that include ligands containing either a single phosphinimine functionality or both a phosphinimine group and a phosphine or arsine group, or an aminato group, or a second phosphinimine moiety. These phosphinimine ligands are complexed to early transition metal radionuclides (e.g., {sup 99m}Tc or {sup 186}Re/{sup 188}Re) or late transition metals (e.g., {sup 105}Rh or {sup 109}Pd). The complexes with these metals {sup 186}Re/{sup 188}Re, {sup 99m}Tc and {sup 109}Pd exhibit a high in vitro and high in vivo stability. The complexes are formed in high yields and can be neutral or charged. These ligands can also be used to form stable compounds with paramagnetic transition metals (e.g., Fe and Mn) for potential use as MRI contrast agents. Applications for the use of ligands and making the ligands are also disclosed.

Evaluation of Acridine Orange Derivatives as DNA-Targeted Radiopharmaceuticals for Auger Therapy: Influence of the Radionuclide and Distance to DNA

PubMed Central

Pereira, Edgar; do Quental, Letícia; Palma, Elisa; Oliveira, Maria Cristina; Mendes, Filipa; Raposinho, Paula; Correia, Isabel; Lavrado, João; Di Maria, Salvatore; Belchior, Ana; Vaz, Pedro; Santos, Isabel; Paulo, António

2017-01-01

A new family of 99mTc(I)- tricarbonyl complexes and 125I-heteroaromatic compounds bearing an acridine orange (AO) DNA targeting unit was evaluated for Auger therapy. Characterization of the DNA interaction, performed with the non-radioactive Re and 127I congeners, confirmed that all compounds act as DNA intercalators. Both classes of compounds induce double strand breaks (DSB) in plasmid DNA but the extent of DNA damage is strongly dependent on the linker between the Auger emitter (99mTc or 125I) and the AO moiety. The in vitro evaluation was complemented with molecular docking studies and Monte Carlo simulations of the energy deposited at the nanometric scale, which corroborated the experimental data. Two of the tested compounds, 125I-C5 and 99mTc-C3, place the corresponding radionuclide at similar distances to DNA and produce comparable DSB yields in plasmid and cellular DNA. These results provide the first evidence that 99mTc can induce DNA damage with similar efficiency to that of 125I, when both are positioned at comparable distances to the double helix. Furthermore, the high nuclear retention of 99mTc-C3 in tumoral cells suggests that 99mTc-labelled AO derivatives are more promising for the design of Auger-emitting radiopharmaceuticals than the 125I-labelled congeners. PMID:28211920

Zeeman relaxation of cold atomic iron and nickel in collisions with He3

NASA Astrophysics Data System (ADS)

Johnson, Cort; Newman, Bonna; Brahms, Nathan; Doyle, John M.; Kleppner, Daniel; Greytak, Thomas J.

2010-06-01

We have measured the ratio γ of the diffusion cross section to the angular momentum reorientation cross section in the colliding Fe-He3 and Ni-He3 systems. Nickel (Ni) and iron (Fe) atoms are introduced via laser ablation into a cryogenically cooled experimental cell containing cold (<1 K) He3 buffer gas. Elastic collisions rapidly cool the translational temperature of the ablated atoms to the He3 temperature. γ is extracted by measuring the decays of the atomic Zeeman sublevels. For our experimental conditions, thermal energy is comparable to the Zeeman splitting. As a result, thermal excitations between Zeeman sublevels significantly impact the observed decay. To determine γ accurately, we introduce a model of Zeeman-state dynamics that includes thermal excitations. We find γNi-3He=5×103 and γFe-3He⩽3×103 at 0.75 K in a 0.8-T magnetic field. These measurements are interpreted in the context of submerged shell suppression of spin relaxation, as studied previously in transition metals and rare-earth-metal atoms [C. I. Hancox, S. C. Doret, M. T. Hummon, R. V. Krems, and J. M. Doyle, Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.94.013201 94, 013201 (2005); C. I. Hancox, S. C. Doret, M. T. Hummon, L. Luo, and J. M. Doyle, Nature (London)NATUAS0028-083610.1038/nature02938 431, 281 (2004); A. Buchachenko, G. Chaasiski, and M. Szczniak, Eur. Phys. J. DEPJDF61434-606010.1140/epjd/e2006-00263-3 45, 147 (2007)].

Bimetallic Porous Iron (pFe) Materials for Remediation/Removal of Tc from Aqueous Systems

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

Li, D.

Remediation of Tc remains an unresolved challenge at SRS and other DOE sites. The objective of this project was to develop novel bimetallic porous iron (pFe) materials for Tc removal from aqueous systems. We showed that the pFe is much more effective in removing TcO 4 - (×30) and ReO 4 - (×8) from artificial groundwater than granular iron. Tc K-edge XANES spectroscopy indicated that Tc speciation on the pFe was 18% adsorbed TcO 4 -, 28% Tc(IV) in Tc dioxide and 54% Tc(IV) into the structure of Fe hydroxide. A variety of catalytic metal nanoparticles (i.e., Ni, Cu, Zn,more » Ag, Sn and Pd) were successfully deposited on the pFe using scalable chemical reduction methods. The Zn-pFe was outstanding among the six bimetallic pFe materials, with a capacity increase of >100% for TcO 4 - removal and of 50% for ReO 4 - removal, compared to the pFe. These results provide a highly applicable platform for solving critical DOE and industrial needs related to nuclear environmental stewardship and nuclear power production.« less

Novel Metal Ion Based Estrogen Mimics for Molecular Imaging

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

Rajagopalan, Raghavan

The overall objective of the SBIR Phase I proposal is to prepare and evaluate a new class of {sup 99m}Tc or {sup 94m}Tc containing estrogen-like small molecules ('estrogen mimics') for SPECT or PET molecular imaging of estrogen receptor positive (ER+) tumors. In this approach, the metal ion is integrated into the estrone skeleton by isosteric substitution of a carbon atom in the steroidal structure to give new class of mimics that are topologically similar to the native estrogen (Fig. 1). Although both N{sub 2}S{sub 2} and N{sub 3}S mimics 1 and 2 were considered as target structures, molecular modeling studymore » revealed that the presence of the acetyl group at position-15 in the N{sub 3}S mimic 2 causes steric hinderance toward binding of 2 to SHBG. Therefore, initial efforts were directed at the synthesis and evaluation of the N{sub 2}S{sub 2} mimic 1.« less

Pressure-induced zigzag phosphorus chain and superconductivity in boron monophosphide.

PubMed

Zhang, Xinyu; Qin, Jiaqian; Liu, Hanyu; Zhang, Shiliang; Ma, Mingzhen; Luo, Wei; Liu, Riping; Ahuja, Rajeev

2015-03-04

We report on the prediction of the zinc-blende structure BP into a novel C2/m phase from 113 to 208 GPa which possesses zigzag phosphorus chain structure, followed by another P42/mnm structure above 208 GPa above using the particle-swarm search method. Strong electron-phonon coupling λ in compressed BP is found, in particular for C2/m phase with the zigzag phosphorus chain, which has the highest λ (0.56-0.61) value among them, leading to its high superconducting critical temperature Tc (9.4 K-11.5 K), which is comparable with the 4.5 K to 13 K value of black phosphorus phase I (orthorhombic, Cmca). This is the first system in the boron phosphides which shows superconductivity from the present theoretical calculations. Our results show that pressure-induced zigzag phosphorus chain in BP exhibit higher superconducting temperature TC, opening a new route to search and design new superconductor materials with zigzag phosphorus chains.

Experimental study of {sup 99m}Tc-aluminum oxide use for sentinel lymph nodes detection

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

Chernov, V. I., E-mail: Chernov@oncology.tomsk.ru; Sinilkin, I. G.; Zelchan, R. V.

The purpose of the study was a comparative research in the possibility of using the radiopharmaceuticals {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis for visualizing sentinel lymph nodes. The measurement of the sizes of {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis colloidal particles was performed in seven series of radiopharmaceuticals. The pharmacokinetics of {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis was researched on 50 white male rats. The possibility of the use of {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis for lymphoscintigraphy was studied in the experiments on 12 white male rats. The average dynamic diameter of the sol particlemore » was 52–77 nm for {sup 99m}Tc-Al{sub 2}O{sub 3} and 16.7–24.5 nm for {sup 99m}Tc-Nanocis. Radiopharmaceuticals accumulated in the inguinal lymph node in 1 hour after administration; the average uptake of {sup 99}mTc-Al{sub 2}O{sub 3} was 8.6% in it, and the accumulation of {sup 99m}Tc-Nanocis was significantly lower—1.8% (p < 0.05). In all study points the average uptake of {sup 99m}Tc-Al{sub 2}O{sub 3} in the lymph node was significantly higher than {sup 99m}Tc-Nanocis accumulation. The results of dynamic scintigraphic studies in rats showed that {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis actively accumulated into the lymphatic system. By using {sup 99m}Tc-Al{sub 2}O{sub 3} inguinal lymph node was determined in 5 minutes after injection and clearly visualized in all the animals in the 15th minute, when the accumulation became more than 1% of the administered dose. Further observation indicated that the {sup 99m}Tc-Al{sub 2}O{sub 3} accumulation reached a plateau in a lymph node (average 10.5%) during 2-hour study and then its accumulation remained practically at the same level, slightly increasing to 12% in 24 hours. In case of {sup 99m}Tc-Nanocis inguinal lymph node was visualized in all animals for 15 min when it was accumulated on the average 1.03% of the administered dose. Plateau of {sup 99m}Tc-Nanocis accumulation in the lymph node (average 2.05%) occurred after 2 hours of the study and remained almost on the same level (in average 2.3%) for 24 hours. Thus, the experimental study of a new domestic radiopharmaceutical showed that the {sup 99m}Tc-Al{sub 2}O{sub 3} accumulates actively in the lymph nodes several times as compared to the imported analogue and its practical application will facilitate intraoperative identification of sentinel lymph nodes.« less

Evidence for hydrodynamic electron flow in PdCoO₂.

PubMed

Moll, Philip J W; Kushwaha, Pallavi; Nandi, Nabhanila; Schmidt, Burkhard; Mackenzie, Andrew P

2016-03-04

Electron transport is conventionally determined by the momentum-relaxing scattering of electrons by the host solid and its excitations. Hydrodynamic fluid flow through channels, in contrast, is determined partly by the viscosity of the fluid, which is governed by momentum-conserving internal collisions. A long-standing question in the physics of solids has been whether the viscosity of the electron fluid plays an observable role in determining the resistance. We report experimental evidence that the resistance of restricted channels of the ultrapure two-dimensional metal palladium cobaltate (PdCoO2) has a large viscous contribution. Comparison with theory allows an estimate of the electronic viscosity in the range between 6 × 10(-3) kg m(-1) s(-1) and 3 × 10(-4) kg m(-1) s(-1), versus 1 × 10(-3) kg m(-1) s(-1) for water at room temperature. Copyright © 2016, American Association for the Advancement of Science.

Prevalence and Mutation Patterns of HIV Drug Resistance from 2010 to 2011 among ART-Failure Individuals in the Yunnan Province, China

PubMed Central

Guo, Wei; Zhuang, Daomin; Li, Lin; Liu, Yongjian; Bao, Zuoyi; Liu, Siyang; Wang, Xiaolin; Li, Tianyi; Yang, Shaomin; Li, Jingyun

2013-01-01

Background Assessing the prevalence of HIV-1 drug-resistance and the mutation patterns associated with resistance in the geographical regions implementing free antiretroviral therapy (ART) in China is necessary for preventing the spread of resistant strains and designing the regimens for the subsequent therapies with limited resources. Methods Plasma samples in different cities/prefectures were collected at Yunnan Provincial Hospital of Infectious Disease from January 2010 to December 2011. Genotyping of drug-resistant individuals was conducted using an in-house assay on plasma samples. Viral load, CD4 T cell counts and demographic data were obtained from medical records and an administered questionnaire. Results A total of 609 pol sequences (515 ART-failure and 94 therapy-naïve individuals) derived from 664 samples were obtained. The prevalence of drug-resistance was 45.1% in the ART-failure individuals. Of these, 26.8% harbored HIV strains dually resistant to nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors, and 14.8% harbored HIV strains resistant to only one drug category. Mutations such as M184V/I, K103N, V106A, Y181C and G190A were common among the ART-failure individuals, and the frequencies of M184V/I, K103N and V106A were 28.2%, 19.2%, and 22.1%, respectively. The percentages of individuals exhibiting intermediate or high-level resistance to 3TC, FTC, EFV and NVP drugs were 28.4%, 28.2%, 37.3%, and 37.5%, respectively. Factors such as ethnicity, transmission route, CD4 counts, viral load and the duration of ART were significantly correlated with development of drug resistance in the ART-failure individuals. Conclusions The high prevalence of HIV drug-resistance observed among the ART-failure individuals from 2010 to 2011 in Yunnan province should be of increasing concern in regions where the implementation of ART is widespread. Education about the risk factors associated with HIV drug resistance is important for preventing and controlling the spread of HIV drug-resistant strains. PMID:24009694

PD-L1 promoter methylation is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy.

PubMed

Gevensleben, Heidrun; Holmes, Emily Eva; Goltz, Diane; Dietrich, Jörn; Sailer, Verena; Ellinger, Jörg; Dietrich, Dimo; Kristiansen, Glen

2016-11-29

The rapid development of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has generated an urgent need for biomarkers assisting the selection of patients eligible for therapy. The use of PD-L1 immunohistochemistry, which has been suggested as a predictive biomarker, however, is confounded by multiple unresolved issues. The aim of this study therefore was to quantify PD-L1 DNA methylation (mPD-L1) in prostate tissue samples and to evaluate its potential as a biomarker in prostate cancer (PCa). In the training cohort, normal tissue showed significantly lower levels of mPD-L1 compared to tumor tissue. High mPD-L1 in PCa was associated with biochemical recurrence (BCR) in univariate Cox proportional hazards (hazard ratio (HR)=2.60 [95%CI: 1.50-4.51], p=0.001) and Kaplan-Meier analyses (p<0.001). These results were corroborated in an independent validation cohort in univariate Cox (HR=1.24 [95%CI: 1.08-1.43], p=0.002) and Kaplan-Meier analyses (p=0.029). Although mPD-L1 and PD-L1 protein expression did not correlate in the validation cohort, both parameters added significant prognostic information in bivariate Cox analysis (HR=1.22 [95%CI: 1.05-1.42], p=0.008 for mPD-L1 and HR=2.58 [95%CI: 1.43-4.63], p=0.002 for PD-L1 protein expression). mPD-L1 was analyzed in a training cohort from The Cancer Genome Atlas (n=498) and was subsequently measured in an independent validation cohort (n=299) by quantitative methylation-specific real-time PCR. All patients had undergone radical prostatectomy. mPD-L1 is a promising biomarker for the risk stratification of PCa patients and might offer additional relevant prognostic information to the implemented clinical parameters, particularly in the setting of immune checkpoint inhibition.

Percutaneous ethanol injection of hyperfunctioning thyroid nodules: long-term follow-up in 125 patients.

PubMed

Tarantino, Luciano; Francica, Giampiero; Sordelli, Ignazio; Sperlongano, Pasquale; Parmeggiani, Domenico; Ripa, Carmine; Parmeggiani, Umberto

2008-03-01

The purpose of this study was to assess the long-term efficacy of percutaneous ethanol injection (PEI) for the treatment of hyperfunctioning thyroid nodules. One hundred twenty-five patients (88 women, 37 men; age range, 17-76 years; mean age, 53 years) with 127 hyperfunctioning thyroid nodules (volume, 1.2-90 mL; mean, 10.3 mL) were treated with PEI. There were 1-11 PEI sessions per patient (average, 3.9) performed, with injection of 1-14 mL of ethanol per session (total injected ethanol per patient, 3-108 mL; mean, 14.0 mL). Efficacy of the treatment was assessed with color Doppler sonography; scintigraphy; and free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) assays. Follow-up (9-144 months; median, 60 months) was performed with TSH and color Doppler sonography every 2 months for 6 months and every 6 months thereafter. Three (2.4%) of 125 patients refused completion of PEI therapy because of pain. Results are reported in 122 patients with 124 nodules. All 122 patients showed posttreatment normal levels of FT3, FT4, and TSH. A complete cure (absent uptake in the nodule and recovery of normal uptake in the thyroid parenchyma) was obtained in 113 (93%) of 122 patients-115 (92.7%) of 124 treated nodules. Residual hyperfunctioning nodular tissue along with decreased thyroid parenchyma uptake (partial cure) was present in nine patients accounting for nine (7.3%) of 124 nodules. Rates of complete cure after PEI were: overall nodules, 115 (92.7%) of 124; nodules < or = 10 mL, 63 (94.0%) of 67; nodules > 10 to < or = 30 mL, 32 (91.4%) of 35; nodules > 30 to < or = 60 mL, 17 (89.5%) of 19; nodules > 60 mL, three (100%) of three. The overall rate of major complications (transient laryngeal nerve damage, two patients; abscess and hematoma, one patient each) was four (3.2%) of 125 patients. Follow-up examinations showed marked shrinkage of 112 treated nodules ranging from 50% to 90% of the pretreatment volume (mean, 66%) and new growth of hyperfunctioning tissue in four patients at color Doppler sonography and scintigraphy at 12, 18, 18, and 48 months' follow-up, respectively. However, all patients remained euthyroid (low or normal TSH and normal FT3 and FT4) during follow-up. PEI of hyperfunctioning thyroid nodules seems to be an effective and safe alternative to traditional treatment. It also appears to be effective in patients with hyperfunctioning thyroid nodules larger than 30 mL.

Simple methodology to directly genotype Trypanosoma cruzi discrete typing units in single and mixed infections from human blood samples.

PubMed

Bontempi, Iván A; Bizai, María L; Ortiz, Sylvia; Manattini, Silvia; Fabbro, Diana; Solari, Aldo; Diez, Cristina

2016-09-01

Different DNA markers to genotype Trypanosoma cruzi are now available. However, due to the low quantity of parasites present in biological samples, DNA markers with high copy number like kinetoplast minicircles are needed. The aim of this study was to complete a DNA assay called minicircle lineage specific-PCR (MLS-PCR) previously developed to genotype the T. cruzi DTUs TcV and TcVI, in order to genotype DTUs TcI and TcII and to improve TcVI detection. We screened kinetoplast minicircle hypervariable sequences from cloned PCR products from reference strains belonging to the mentioned DTUs using specific kDNA probes. With the four highly specific sequences selected, we designed primers to be used in the MLS-PCR to directly genotype T. cruzi from biological samples. High specificity and sensitivity were obtained when we evaluated the new approach for TcI, TcII, TcV and TcVI genotyping in twenty two T. cruzi reference strains. Afterward, we compared it with hybridization tests using specific kDNA probes in 32 blood samples from chronic chagasic patients from North Eastern Argentina. With both tests we were able to genotype 94% of the samples and the concordance between them was very good (kappa=0.855). The most frequent T. cruzi DTUs detected were TcV and TcVI, followed by TcII and much lower TcI. A unique T. cruzi DTU was detected in 18 samples meantime more than one in the remaining; being TcV and TcVI the most frequent association. A high percentage of mixed detections were obtained with both assays and its impact was discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Scatter and cross-talk corrections in simultaneous Tc-99m/I-123 brain SPECT using constrained factor analysis and artificial neural networks

NASA Astrophysics Data System (ADS)

Fakhri, G. El; Maksud, P.; Kijewski, M. F.; Haberi, M. O.; Todd-Pokropek, A.; Aurengo, A.; Moore, S. C.

2000-08-01

Simultaneous imaging of Tc-99m and I-123 would have a high clinical potential in the assessment of brain perfusion (Tc-99m) and neurotransmission (I-123) but is hindered by cross-talk between the two radionuclides. Monte Carlo simulations of 15 different dual-isotope studies were performed using a digital brain phantom. Several physiologic Tc-99m and I-123 uptake patterns were modeled in the brain structures. Two methods were considered to correct for cross-talk from both scattered and unscattered photons: constrained spectral factor analysis (SFA) and artificial neural networks (ANN). The accuracy and precision of reconstructed pixel values within several brain structures were compared to those obtained with an energy windowing method (WSA). In I-123 images, mean bias was close to 10% in all structures for SFA and ANN and between 14% (in the caudate nucleus) and 25% (in the cerebellum) for WSA. Tc-99m activity was overestimated by 35% in the cortex and 53% in the caudate nucleus with WSA, but by less than 9% in all structures with SFA and ANN. SFA and ANN performed well even in the presence of high-energy I-123 photons. The accuracy was greatly improved by incorporating the contamination into the SFA model or in the learning phase for ANN. SFA and ANN are promising approaches to correct for cross-talk in simultaneous Tc-99m/I-123 SPECT.

Application of ultra-high energy hollow cathode helium-silver laser (224.3 nm) as Jc's, grain size surface's promoter for Ir-optimally doped-Mg0.94Ir0.06B2 superconductors

NASA Astrophysics Data System (ADS)

Elsabawy, Khaled M.; Fallatah, Ahmed M.; Alharthi, Salman S.

2018-07-01

For the first time high energy Helium-Silver laser which belongs to the category of metal-vapor lasers applied as microstructure promoter for optimally Ir-doped-MgB2sample. The Ir-optimally doped-Mg0.94Ir 0.06B2 superconducting sample was selected from previously published article for one of authors themselves. The samples were irradiated by a three different doses 1, 2 and 3 h from an ultrahigh energy He-Ag-Laser with average power of 103 W/cm2 at distance of 3 cm. Superconducting measurements and micro-structural features were investigated as function of He-Ag Laser irradiation doses. Results indicated that irradiations via an ultrahigh energy He-Ag-Laser promoted grains to lower sizes and consequently measured Jc's values enhanced and increased. Furthermore Tc-offsets for all irradiated samples are better than non-irradiated Mg0.94Ir 0.06B2.

Hard beta and gamma emissions of 124I. Impact on occupational dose in PET/CT.

PubMed

Kemerink, G J; Franssen, R; Visser, M G W; Urbach, C J A; Halders, S G E A; Frantzen, M J; Brans, B; Teule, G J J; Mottaghy, F M

2011-01-01

The hard beta and gamma radiation of 124I can cause high doses to PET/CT workers. In this study we tried to quantify this occupational exposure and to optimize radioprotection. Thin MCP-Ns thermoluminescent dosimeters suitable for measuring beta and gamma radiation were used for extremity dosimetry, active personal dosimeters for whole-body dosimetry. Extremity doses were determined during dispensing of 124I and oral administration of the activity to the patient, the body dose during all phases of the PET/CT procedure. In addition, dose rates of vials and syringes as used in clinical practice were measured. The procedure for dispensing 124I was optimized using newly developed shielding. Skin dose rates up to 100 mSv/min were measured when in contact with the manufacturer's vial containing 370 MBq of 124I. For an unshielded 5 ml syringe the positron skin dose was about seven times the gamma dose. Before optimization of the preparation of 124I, using an already reasonably safe technique, the highest mean skin dose caused by handling 370 MBq was 1.9 mSv (max. 4.4 mSv). After optimization the skin dose was below 0.2 mSv. The highly energetic positrons emitted by 124I can cause high skin doses if radioprotection is poor. Under optimized conditions occupational doses are acceptable. Education of workers is of paramount importance.

Hydrolysis mechanisms for the organopalladium complex [Pd(CNN)P(OMe)3]BF4 in sulfuric acid.

PubMed

García, Begoña; Hoyuelos, Francisco J; Ibeas, Saturnino; Muñoz, María S; Peñacoba, Indalecio; Leal, José M

2009-08-13

The acid-catalyzed hydrolysis of the organopalladium complex [Pd(CNN)P(OMe)3]BF4 species was monitored spectrophotometrically at different sulfuric acid concentrations (3.9 and 11.0 M) in 10% v:v ethanol-water over the 25-45 degrees C temperature range and in 30% and 50% (v/v) ethanol-water at 25 degrees C. Two acidity regions (I and II) could be differentiated. In each of the two regions the kinetic data pairs yielded two different rate constants, k(1obs) and k(2obs), the former being faster. These constants were fitted by an Excess Acidity analysis to different hydrolyses mechanisms: A-1, A-2, and A-SE2. In region I ([H2SO4] < 7.0 M), the k(1obs) values remained constant k(1obs)(av) = 1.6 x 10(-3) s(-1) and the set of k(2obs) values nicely matched an A-SE2 mechanism, yielding a rate-determining constant k(0,ASE2) = 2.4 x 10(-7) M(-1) s(-1). In region II ([H2SO4] > 7.0 M), a switchover was observed from an A-1 mechanism (k(0,A1) = 1.3 x 10(-4) s(-1)) to an A-2 mechanism (k(0,A2) = 3.6 x 10(-3) M(-1) s(-1)). The temperature effect on the rate constants in 10% (v/v) ethanol-water yielded positive DeltaH and negative DeltaS values, except for the A-1 mechanism, where DeltaS adopted positive values throughout. The solvent permittivity effect, epsilonr, revealed that k(1obs)(av) and k(0,A2) dropped with a fall in epsilonr, whereas the k(0,ASE2) value remained unaffected. The set of results deduced is in line with the schemes put forward.

Evaluation of technetium-99m decay on Escherichia coli inactivation: effects of physical or chemical agents.

PubMed Central

Silva, C. R.; Valsa, J. O.; Caniné, M. S.; Caldeira-de-Araújo, A.; Bernardo-Filho, M.

1998-01-01

Technetium-99m (99mTc) has been used in nuclear medicine and in biomedical research to label molecular and cellular structures employed as radiotracers. Here, we have evaluated, on a DNA repair proficient Escherichia coli strain, the 99mTc decay inactivation and the influence of the (i) pre-treatment with metal ion chelators or of the (ii) treatment with a free radical scavenger on the protection of the cells against the lethal effect of the 99mTc. As SnCl2 is frequently used as a reducing agent in the 99mTc-labeling process, we have also studied the capability of SnCl2 to alter the biological effects induced by the 99mTc decay. As we are exposed to either chemical or physical agents in the nature, we have decided to study a possible influence of the ultraviolet solar radiation in the biological phenomena induced by the 99mTc decay. Our data point out (i) a very important role of the Auger and/or conversion electrons in the cytotoxicity induced by the 99mTc decay; (ii) SnCl2, the metal ion chelators and the free radical scavenger protect the cells against the lethal effect of the 99mTc; and (iii) near-UV does not alter the lethal effect of the 99mTc decay. PMID:9713950

Free-breathing diffusion-weighted single-shot echo-planar MR imaging using parallel imaging (GRAPPA 2) and high b value for the detection of primary rectal adenocarcinoma.

PubMed

Soyer, Philippe; Lagadec, Matthieu; Sirol, Marc; Dray, Xavier; Duchat, Florent; Vignaud, Alexandre; Fargeaudou, Yann; Placé, Vinciane; Gault, Valérie; Hamzi, Lounis; Pocard, Marc; Boudiaf, Mourad

2010-02-11

Our objective was to determine the diagnostic accuracy of a free-breathing diffusion-weighted single-shot echo-planar magnetic resonance imaging (FBDW-SSEPI) technique with parallel imaging and high diffusion factor value (b = 1000 s/mm2) in the detection of primary rectal adenocarcinomas. Thirty-one patients (14M and 17F; mean age 67 years) with histopathologically proven primary rectal adenocarcinomas and 31 patients without rectal malignancies (14M and 17F; mean age 63.6 years) were examined with FBDW-SSEPI (repetition time (TR/echo time (TE) 3900/91 ms, gradient strength 45 mT/m, acquisition time 2 min) at 1.5 T using generalized autocalibrating partially parallel acquisitions (GRAPPA, acceleration factor 2) and a b value of 1000 s/mm2. Apparent diffusion coefficients (ADCs) of rectal adenocarcinomas and normal rectal wall were measured. FBDW-SSEPI images were evaluated for tumour detection by 2 readers. Sensitivity, specificity, accuracy and Youden score for rectal adenocarcinoma detection were calculated with their 95% confidence intervals (CI) for ADC value measurement and visual image analysis. Rectal adenocarcinomas had significantly lower ADCs (mean 1.036 x 10(-3)+/- 0.107 x 10(-3) mm2/s; median 1.015 x 10(-3) mm2/s; range (0.827-1.239) x 10(-3) mm2/s) compared with the rectal wall of control subjects (mean 1.387 x 10(-3)+/- 0.106 x 10(-3) mm2/s; median 1.385 x 10(-3) mm2/s; range (1.176-1.612) x 10(-3) mm2/s) (p < 0.0001). Using a threshold value < or = 1.240 x 10(-3) mm2/s, all rectal adenocarcinomas were correctly categorized and 100% sensitivity (31/31; 95% CI 95-100%), 94% specificity (31/33; 95% CI 88-100%), 97% accuracy (60/62; 95% CI 92-100%) and Youden index 0.94 were obtained for the diagnosis of rectal adenocarcinoma. FBDW-SSEPI image analysis allowed depiction of all rectal adenocarcinomas but resulted in 2 false-positive findings, yielding 100% sensitivity (31/31; 95% CI 95-100%), 94% specificity (31/33; 95% CI 88-100%), 97% accuracy (60/62; 95% CI 92-100%) and Youden index 0.94 for the diagnosis of primary rectal adenocarcinoma. We can conclude that FBDW-SSEPI using parallel imaging and high b value may be helpful in the detection of primary rectal adenocarcinomas.

Synthesis and characterization of fac-[M(CO)3(P)(OO)] and cis-trans-[M(CO)2(P)2(OO)] complexes (M = Re, (99m)Tc) with acetylacetone and curcumin as OO donor bidentate ligands.

PubMed

Triantis, Charalampos; Tsotakos, Theodoros; Tsoukalas, Charalampos; Sagnou, Marina; Raptopoulou, Catherine; Terzis, Aris; Psycharis, Vassilis; Pelecanou, Maria; Pirmettis, Ioannis; Papadopoulos, Minas

2013-11-18

The synthesis and characterization of neutral mixed ligand complexes fac-[M(CO)3(P)(OO)] and cis-trans-[M(CO)2(P)2(OO)] (M = Re, (99m)Tc), with deprotonated acetylacetone or curcumin as the OO donor bidentate ligands and a phosphine (triphenylphosphine or methyldiphenylphosphine) as the monodentate P ligand, is described. The complexes were synthesized through the corresponding fac-[M(CO)3(H2O)(OO)] (M = Re, (99m)Tc) intermediate aqua complex. In the presence of phosphine, replacement of the H2O molecule of the intermediate complex at room temperature generates the neutral tricarbonyl monophosphine fac-[Re(CO)3(P)(OO)] complex, while under reflux conditions further replacement of the trans to the phosphine carbonyl generates the new stable dicarbonyl bisphosphine complex cis-trans-[Re(CO)2(P)2(OO)]. The Re complexes were fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography showing a distorted octahedral geometry around Re. Both the monophosphine and the bisphosphine complexes of curcumin show selective binding to β-amyloid plaques of Alzheimer's disease. At the (99m)Tc tracer level, the same type of complexes, fac-[(99m)Tc(CO)3(P)(OO)] and cis-trans-[(99m)Tc(CO)2(P)2(OO)], are formed introducing new donor combinations for (99m)Tc(I). Overall, β-diketonate and phosphine constitute a versatile ligand combination for Re(I) and (99m)Tc(I), and the successful employment of the multipotent curcumin as β-diketone provides a solid example of the pharmacological potential of this system.

Differences between the macroscopic and tracer level chemistry of rhenium and technetium: contrasting cage isomerisation behaviour of Re(I) and Tc(I) carborane complexes.

PubMed

Armstrong, Andrea F; Valliant, John F

2010-09-21

Carboranes form stable complexes with the [M(CO)(3)](+) (M = (99m)Tc, Re) core and are viable ligands for the development of targeted radiopharmaceuticals. (99m)Tc-carborane complexes were found to exhibit substantially different 1,2-->1,7 cage isomerisation behaviour than their Re counterparts, challenging the validity of the routine use of rhenium as a surrogate for the development of technetium-99m based molecular imaging agents.

On determining dose rate constants spectroscopically

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

Rodriguez, M.; Rogers, D. W. O.

2013-01-15

Purpose: To investigate several aspects of the Chen and Nath spectroscopic method of determining the dose rate constants of {sup 125}I and {sup 103}Pd seeds [Z. Chen and R. Nath, Phys. Med. Biol. 55, 6089-6104 (2010)] including the accuracy of using a line or dual-point source approximation as done in their method, and the accuracy of ignoring the effects of the scattered photons in the spectra. Additionally, the authors investigate the accuracy of the literature's many different spectra for bare, i.e., unencapsulated {sup 125}I and {sup 103}Pd sources. Methods: Spectra generated by 14 {sup 125}I and 6 {sup 103}Pd seedsmore » were calculated in vacuo at 10 cm from the source in a 2.7 Multiplication-Sign 2.7 Multiplication-Sign 0.05 cm{sup 3} voxel using the EGSnrc BrachyDose Monte Carlo code. Calculated spectra used the initial photon spectra recommended by AAPM's TG-43U1 and NCRP (National Council of Radiation Protection and Measurements) Report 58 for the {sup 125}I seeds, or TG-43U1 and NNDC(2000) (National Nuclear Data Center, 2000) for {sup 103}Pd seeds. The emitted spectra were treated as coming from a line or dual-point source in a Monte Carlo simulation to calculate the dose rate constant. The TG-43U1 definition of the dose rate constant was used. These calculations were performed using the full spectrum including scattered photons or using only the main peaks in the spectrum as done experimentally. Statistical uncertainties on the air kerma/history and the dose rate/history were Less-Than-Or-Slanted-Equal-To 0.2%. The dose rate constants were also calculated using Monte Carlo simulations of the full seed model. Results: The ratio of the intensity of the 31 keV line relative to that of the main peak in {sup 125}I spectra is, on average, 6.8% higher when calculated with the NCRP Report 58 initial spectrum vs that calculated with TG-43U1 initial spectrum. The {sup 103}Pd spectra exhibit an average 6.2% decrease in the 22.9 keV line relative to the main peak when calculated with the TG-43U1 rather than the NNDC(2000) initial spectrum. The measured values from three different investigations are in much better agreement with the calculations using the NCRP Report 58 and NNDC(2000) initial spectra with average discrepancies of 0.9% and 1.7% for the {sup 125}I and {sup 103}Pd seeds, respectively. However, there are no differences in the calculated TG-43U1 brachytherapy parameters using either initial spectrum in both cases. Similarly, there were no differences outside the statistical uncertainties of 0.1% or 0.2%, in the average energy, air kerma/history, dose rate/history, and dose rate constant when calculated using either the full photon spectrum or the main-peaks-only spectrum. Conclusions: Our calculated dose rate constants based on using the calculated on-axis spectrum and a line or dual-point source model are in excellent agreement (0.5% on average) with the values of Chen and Nath, verifying the accuracy of their more approximate method of going from the spectrum to the dose rate constant. However, the dose rate constants based on full seed models differ by between +4.6% and -1.5% from those based on the line or dual-point source approximations. These results suggest that the main value of spectroscopic measurements is to verify full Monte Carlo models of the seeds by comparison to the calculated spectra.« less

Imaging of mild traumatic brain injury using 57Co and 99mTc HMPAO SPECT as compared to other diagnostic procedures.

PubMed

Audenaert, Kurt; Jansen, Hugo M L; Otte, Andreas; Peremans, Kathelijne; Vervaet, Myriam; Crombez, Roger; de Ridder, Leo; van Heeringen, Cees; Thirot, Joel; Dierckx, Rudi; Korf, Jaap

2003-10-01

Traumatic brain injury (TBI) is usually assessed with the Glasgow Coma Scale (GCS), CT and EEG. TBI can result from either the primary mechanical impact or secondary (ischemic) brain damage, in which calcium (Ca) plays a pivotal role. This study was undertaken to compare the applicability of SPECT using 57Co as a Ca-tracer in patients with mild traumatic brain injury. 8 patients with mild TBI (GCS 15) were clinically examined and studied with EEG, neuropsychological testing (NPT) and SPECT within 2 days post-TBI. After i.v.-administration of 37 MBq (1 mCi) 57Co (effective radiation dose 0.34 mSv x MBq(-1); 1.24 rem x mCi(-1); physical half-life 270 days, biological half-life 37.6 h), single-headed SPECT (12 h pi) was performed, consecutively followed by standard 925 MBq (25 mCi) Tc-99m HMPAO SPECT. In 6 of the 8 patients, baseline NPT and SPECT showed focal abnormalities in the affected frontal and temporal brain regions, which were in good topographical accordance. CT and EEG did not detect (structural) lesions in any of these cases. Single-headed 57Co-SPECT is able to show the site and extent of brain damage in patients with mild TBI, even in the absence of structural lesions. It may confirm and localize NPT findings. The predictive value of 57Co-SPECT should be assessed in larger patient series.

An Introduction to Structural Reliability Theory

DTIC Science & Technology

1989-01-01

Test Samples psi COV Distribution Remarks Yield stress 66 (XX 0.09 assumed lognormal mill test I containment vesel SA537 GrB Yield stress 󈧗 6W8...straightened shape Tension :32 57.909 0.089 cold straightened shape Tension 9 84.039 0.1124 annealed , alloy steel Tension 9 124,9 0.1796 . quenched...alloys, annealed and quenched, and drawn samples Tension 22 29.50 X 103 0.0072 .. structural steel Compression 22 29.49 X 103 0.0146 ... structural

SU-E-T-155: Calibration of Variable Longitudinal Strength 103Pd Brachytherapy Sources

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

Reed, J; Radtke, J; Micka, J

Purpose: Brachytherapy sources with variable longitudinal strength (VLS) allow for a customized intensity along the length of the source. These have applications in focal brachytherapy treatments of prostate cancer where dose boosting can be achieved through modulation of intra-source strengths. This work focused on development of a calibration methodology for VLS sources based on measurements and Monte Carlo (MC) simulations of five 1 cm {sup 10} {sup 3}Pd sources each containing four regions of variable {sup 103}Pd strength. Methods: The air-kerma strengths of the sources were measured with a variable-aperture free-air chamber (VAFAC). Source strengths were also measured using amore » well chamber. The in-air azimuthal and polar anisotropy of the sources were measured by rotating them in front of a NaI scintillation detector and were calculated with MC simulations. Azimuthal anisotropy results were normalized to their mean intensity values. Polar anisotropy results were normalized to their average transverse axis intensity values. The relative longitudinal strengths of the sources were measured via on-contact irradiations with radiochromic film, and were calculated with MC simulations. Results: The variable {sup 103}Pd loading of the sources was validated by VAFAC and well chamber measurements. Ratios of VAFAC air-kerma strengths and well chamber responses were within ±1.3% for all sources. Azimuthal anisotropy results indicated that ≥95% of the normalized values for all sources were within ±1.7% of the mean values. Polar anisotropy results indicated variations within ±0.3% for a ±7.6° angular region with respect to the source transverse axis. Locations and intensities of the {sup 103}Pd regions were validated by radiochromic film measurements and MC simulations. Conclusion: The calibration methodology developed in this work confirms that the VLS sources investigated have a high level of polar uniformity, and that the strength and longitudinal intensity can be verified experimentally and through MC simulations. {sup 103}Pd sources were provided by CivaTech Oncology, Inc.« less

A Tc-99m-labeled long chain fatty acid derivative for myocardial imaging.

PubMed

Magata, Yasuhiro; Kawaguchi, Takayoshi; Ukon, Misa; Yamamura, Norio; Uehara, Tomoya; Ogawa, Kazuma; Arano, Yasushi; Temma, Takashi; Mukai, Takahiro; Tadamura, Eiji; Saji, Hideo

2004-01-01

C-11- and I-123-labeled long chain fatty acid derivatives have been reported as useful radiopharmaceuticals for the estimation of myocardial fatty acid metabolism. We have reported that Tc-99m-labeled N-[[[(2-mercaptoethyl)amino]carbonyl]methyl]-N-(2-mercaptoethyl)-6-aminohexanoic acid ([(99m)Tc]MAMA-HA), a medium chain fatty acid derivative, is metabolized by beta-oxidation in the liver and that the MAMA ligand is useful for attaching to the omega-position of fatty acid derivatives as a chelating group for Tc-99m. On the basis of these findings, we focused on developing a Tc-99m-labeled long chain fatty acid derivative that reflected fatty acid metabolism in the myocardium. In this study, we synthesized a dodecanoic acid derivative, MAMA-DA, and a hexadecanoic acid derivative, MAMA-HDA, and performed radiolabeling and biodistribution studies. [(99m)Tc]MAMA-DA and [(99m)Tc]MAMA-HDA were prepared using a ligand-exchange reaction. Biodistribution studies were carried out in normal mice and rats. Then, a high initial uptake of Tc-99m was observed, followed by a rapid clearance from the heart. The maximum heart/blood ratio was 3.6 at 2 min postinjection of [(99m)Tc]MAMA-HDA. These kinetics were similar to those with postinjection of p-[(125)I]iodophenylpentadecanoic acid. Metabolite analysis showed [(99m)Tc]MAMA-HDA was metabolized by beta-oxidation in the body. In conclusion, [(99m)Tc]MAMA-HDA is a promising compound as a long chain fatty acid analogue for estimating beta-oxidation of fatty acid in the heart.

[(124)I]FIAU: Human dosimetry and infection imaging in patients with suspected prosthetic joint infection.

PubMed

Zhang, Xiaoyan M; Zhang, Halle H; McLeroth, Patrick; Berkowitz, Richard D; Mont, Michael A; Stabin, Michael G; Siegel, Barry A; Alavi, Abass; Barnett, T Marc; Gelb, Jeffrey; Petit, Chantal; Spaltro, John; Cho, Steve Y; Pomper, Martin G; Conklin, James J; Bettegowda, Chetan; Saha, Saurabh

2016-05-01

Fialuridine (FIAU) is a nucleoside analog that is a substrate for bacterial thymidine kinase (TK). Once phosphorylated by TK, [(124)I]FIAU becomes trapped within bacteria and can be detected with positron emission tomography/computed tomography (PET/CT). [(124)I]FIAU PET/CT has been shown to detect bacteria in patients with musculoskeletal bacterial infections. Accurate diagnosis of prosthetic joint infections (PJIs) has proven challenging because of the lack of a well-validated reference. In the current study, we assessed biodistribution and dosimetry of [(124)I]FIAU, and investigated whether [(124)I]FIAU PET/CT can diagnose PJIs with acceptable accuracy. To assess biodistribution and dosimetry, six subjects with suspected hip or knee PJI and six healthy subjects underwent serial PET/CT after being dosed with 74MBq (2mCi) [(124)I]FIAU intravenously (IV). Estimated radiation doses were calculated with the OLINDA/EXM software. To determine accuracy of [(124)I]FIAU, 22 subjects with suspected hip or knee PJI were scanned at 2-6 and 24-30h post IV injection of 185MBq (5mCi) [(124)I]FIAU. Images were interpreted by a single reader blinded to clinical information. Representative cases were reviewed by 3 additional readers. The utility of [(124)I]FIAU to detect PJIs was assessed based on the correlation of the patient's infection status with imaging results as determined by an independent adjudication board (IAB). The kidney, liver, spleen, and urinary bladder received the highest radiation doses of [(124)I]FIAU. The effective dose was 0.16 to 0.20mSv/MBq and doses to most organs ranged from 0.11 to 0.76mGy/MBq. PET image quality obtained from PJI patients was confounded by metal artifacts from the prostheses and pronounced FIAU uptake in muscle. Consequently, a correlation with infection status and imaging results could not be established. [(124)I]FIAU was well-tolerated in healthy volunteers and subjects with suspected PJI, and had acceptable dosimetry. However, the utility of [(124)I]FIAU for the clinical detection of PJIs is limited by poor image quality and low specificity. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

7 CFR 94.103 - Analytical methods.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 3 2014-01-01 2014-01-01 false Analytical methods. 94.103 Section 94.103 Agriculture... POULTRY AND EGG PRODUCTS Voluntary Analyses of Egg Products § 94.103 Analytical methods. The analytical methods used by the Science and Technology Division laboratories to perform voluntary analyses for egg...

7 CFR 94.103 - Analytical methods.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Analytical methods. 94.103 Section 94.103 Agriculture... POULTRY AND EGG PRODUCTS Voluntary Analyses of Egg Products § 94.103 Analytical methods. The analytical methods used by the Science and Technology Division laboratories to perform voluntary analyses for egg...

7 CFR 94.103 - Analytical methods.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 3 2011-01-01 2011-01-01 false Analytical methods. 94.103 Section 94.103 Agriculture... POULTRY AND EGG PRODUCTS Voluntary Analyses of Egg Products § 94.103 Analytical methods. The analytical methods used by the Science and Technology Division laboratories to perform voluntary analyses for egg...

7 CFR 94.103 - Analytical methods.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 3 2013-01-01 2013-01-01 false Analytical methods. 94.103 Section 94.103 Agriculture... POULTRY AND EGG PRODUCTS Voluntary Analyses of Egg Products § 94.103 Analytical methods. The analytical methods used by the Science and Technology Division laboratories to perform voluntary analyses for egg...

7 CFR 94.103 - Analytical methods.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 3 2012-01-01 2012-01-01 false Analytical methods. 94.103 Section 94.103 Agriculture... POULTRY AND EGG PRODUCTS Voluntary Analyses of Egg Products § 94.103 Analytical methods. The analytical methods used by the Science and Technology Division laboratories to perform voluntary analyses for egg...

Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial.

PubMed

Fehrenbacher, Louis; Spira, Alexander; Ballinger, Marcus; Kowanetz, Marcin; Vansteenkiste, Johan; Mazieres, Julien; Park, Keunchil; Smith, David; Artal-Cortes, Angel; Lewanski, Conrad; Braiteh, Fadi; Waterkamp, Daniel; He, Pei; Zou, Wei; Chen, Daniel S; Yi, Jing; Sandler, Alan; Rittmeyer, Achim

2016-04-30

Outcomes are poor for patients with previously treated, advanced or metastatic non-small-cell lung cancer (NSCLC). The anti-programmed death ligand 1 (PD-L1) antibody atezolizumab is clinically active against cancer, including NSCLC, especially cancers expressing PD-L1 on tumour cells, tumour-infiltrating immune cells, or both. We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC, analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population. In this open-label, phase 2 randomised controlled trial, patients with NSCLC who progressed on post-platinum chemotherapy were recruited in 61 academic medical centres and community oncology practices across 13 countries in Europe and North America. Key inclusion criteria were Eastern Cooperative Oncology Group performance status 0 or 1, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), and adequate haematological and end-organ function. Patients were stratified by PD-L1 tumour-infiltrating immune cell status, histology, and previous lines of therapy, and randomly assigned (1:1) by permuted block randomisation (with a block size of four) using an interactive voice or web system to receive intravenous atezolizumab 1200 mg or docetaxel 75 mg/m(2) once every 3 weeks. Baseline PD-L1 expression was scored by immunohistochemistry in tumour cells (as percentage of PD-L1-expressing tumour cells TC3≥50%, TC2≥5% and <50%, TC1≥1% and <5%, and TC0<1%) and tumour-infiltrating immune cells (as percentage of tumour area: IC3≥10%, IC2≥5% and <10%, IC1≥1% and <5%, and IC0<1%). The primary endpoint was overall survival in the intention-to-treat population and PD-L1 subgroups at 173 deaths. Biomarkers were assessed in an exploratory analysis. We assessed safety in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01903993. Patients were enrolled between Aug 5, 2013, and March 31, 2014. 144 patients were randomly allocated to the atezolizumab group, and 143 to the docetaxel group. 142 patients received at least one dose of atezolizumab and 135 received docetaxel. Overall survival in the intention-to-treat population was 12·6 months (95% CI 9·7-16·4) for atezolizumab versus 9·7 months (8·6-12·0) for docetaxel (hazard ratio [HR] 0·73 [95% CI 0·53-0·99]; p=0·04). Increasing improvement in overall survival was associated with increasing PD-L1 expression (TC3 or IC3 HR 0·49 [0·22-1·07; p=0·068], TC2/3 or IC2/3 HR 0·54 [0·33-0·89; p=0·014], TC1/2/3 or IC1/2/3 HR 0·59 [0·40-0·85; p=0·005], TC0 and IC0 HR 1·04 [0·62-1·75; p=0·871]). In our exploratory analysis, patients with pre-existing immunity, defined by high T-effector-interferon-γ-associated gene expression, had improved overall survival with atezolizumab. 11 (8%) patients in the atezolizumab group discontinued because of adverse events versus 30 (22%) patients in the docetaxel group. 16 (11%) patients in the atezolizumab group versus 52 (39%) patients in the docetaxel group had treatment-related grade 3-4 adverse events, and one (<1%) patient in the atezolizumab group versus three (2%) patients in the docetaxel group died from a treatment-related adverse event. Atezolizumab significantly improved survival compared with docetaxel in patients with previously treated NSCLC. Improvement correlated with PD-L1 immunohistochemistry expression on tumour cells and tumour-infiltrating immune cells, suggesting that PD-L1 expression is predictive for atezolizumab benefit. Atezolizumab was well tolerated, with a safety profile distinct from chemotherapy. F Hoffmann-La Roche/Genentech Inc. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of Pt substitution on magnetic properties of multipolar ordering compounds Ce(Pd,Pt)3S4

NASA Astrophysics Data System (ADS)

Michimura, S.; Nishikawa, Ushio; Shimizu, Akihide; Kosaka, Masashi; Numakura, Ryosuke; Iizuka, Ryosuke; Katano, Susumu

2018-05-01

We have studied the magnetic properties of the multipolar ordering compounds Ce(Pd1-xPtx) 3S4 with 0.00 ≤ x ≤ 0.53 by means of magnetic susceptibility and magnetization measurements. In CePd3S4 , a simultaneous phase transition of the antiferro quadrupolar (AFQ) ordering and ferro magnetic (FM) ordering has been observed at 6.3 K. It has been suggested that the primary order parameter of CePd3S4 is the quadrupole moments, and it has not been understood why the FM ordering occurs at very high temperature which is almost the same magnetic transition temperature of GdPd3S4 . GdPd3S4 shows an antiferromagnetic (AFM) transition at 5.8 K. With increasing Pt substitution in CePd3S4 , the FM transition temperature TC (x) is rapidly suppressed to 2.4 K for x ≃ 0.3 and approaches asymptotically to 1.9 K (x = 0.53) . The results of magnetization curve suggest that the ordered state below TC (x) remains FM and AFQ ordered state for the whole range of x. For x ≥ 0.29 , TC (x) reaches at around 2 K, a new AFM transition was observed at TN (x) ≃ 7 K . We determined the T - x phase diagram, and discuss the phase transitions at TC (x) and TN (x) . The results suggest the possibility of the presence of the correlation between the magnetic interaction and the quadrupole interaction, and the correlation is not understood based on the previous multipolar model.

Comparison of TG-43 dosimetric parameters of brachytherapy sources obtained by three different versions of MCNP codes.

PubMed

Zaker, Neda; Zehtabian, Mehdi; Sina, Sedigheh; Koontz, Craig; Meigooni, Ali S

2016-03-08

Monte Carlo simulations are widely used for calculation of the dosimetric parameters of brachytherapy sources. MCNP4C2, MCNP5, MCNPX, EGS4, EGSnrc, PTRAN, and GEANT4 are among the most commonly used codes in this field. Each of these codes utilizes a cross-sectional library for the purpose of simulating different elements and materials with complex chemical compositions. The accuracies of the final outcomes of these simulations are very sensitive to the accuracies of the cross-sectional libraries. Several investigators have shown that inaccuracies of some of the cross section files have led to errors in 125I and 103Pd parameters. The purpose of this study is to compare the dosimetric parameters of sample brachytherapy sources, calculated with three different versions of the MCNP code - MCNP4C, MCNP5, and MCNPX. In these simulations for each source type, the source and phantom geometries, as well as the number of the photons, were kept identical, thus eliminating the possible uncertainties. The results of these investigations indicate that for low-energy sources such as 125I and 103Pd there are discrepancies in gL(r) values. Discrepancies up to 21.7% and 28% are observed between MCNP4C and other codes at a distance of 6 cm for 103Pd and 10 cm for 125I from the source, respectively. However, for higher energy sources, the discrepancies in gL(r) values are less than 1.1% for 192Ir and less than 1.2% for 137Cs between the three codes.

Scatter and cross-talk correction for one-day acquisition of 123I-BMIPP and 99mtc-tetrofosmin myocardial SPECT.

PubMed

Kaneta, Tomohiro; Kurihara, Hideyuki; Hakamatsuka, Takashi; Ito, Hiroshi; Maruoka, Shin; Fukuda, Hiroshi; Takahashi, Shoki; Yamada, Shogo

2004-12-01

123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and 99mTc-tetrofosmin (TET) are widely used for evaluation of myocardial fatty acid metabolism and perfusion, respectively. ECG-gated TET SPECT is also used for evaluation of myocardial wall motion. These tests are often performed on the same day to minimize both the time required and inconvenience to patients and medical staff. However, as 123I and 99mTc have similar emission energies (159 keV and 140 keV, respectively), it is necessary to consider not only scattered photons, but also primary photons of each radionuclide detected in the wrong window (cross-talk). In this study, we developed and evaluated the effectiveness of a new scatter and cross-talk correction imaging protocol. Fourteen patients with ischemic heart disease or heart failure (8 men and 6 women with a mean age of 69.4 yr, ranging from 45 to 94 yr) were enrolled in this study. In the routine one-day acquisition protocol, BMIPP SPECT was performed in the morning, with TET SPECT performed 4 h later. An additional SPECT was performed just before injection of TET with the energy window for 99mTc. These data correspond to the scatter and cross-talk factor of the next TET SPECT. The correction was performed by subtraction of the scatter and cross-talk factor from TET SPECT. Data are presented as means +/- S.E. Statistical analyses were performed using Wilcoxon's matched-pairs signed-ranks test, and p < 0.05 was considered significant. The percentage of scatter and cross-talk relative to the corrected total count was 26.0 +/- 5.3%. EDV and ESV after correction were significantly greater than those before correction (p = 0.019 and 0.016, respectively). After correction, EF was smaller than that before correction, but the difference was not significant. Perfusion scores (17 segments per heart) were significantly lower after as compared with those before correction (p < 0.001). Scatter and cross-talk correction revealed significant differences in EDV, ESV, and perfusion scores. These observations indicate that scatter and cross-talk correction is required for one-day acquisition of 123I-BMIPP and 99mTc-tetrofosmin SPECT.

Longitudinal Trend in Lipid Profile of Incident Peritoneal Dialysis Patients is Not Influenced by the Use of Biocompatible Solutions

PubMed Central

Cho, Yeoungjee; Büchel, Janine; Steppan, Sonja; Passlick-Deetjen, Jutta; Hawley, Carmel M.; Dimeski, Goce; Clarke, Margaret; Johnson, David W.

2016-01-01

♦ Background: The longitudinal trends of lipid parameters and the impact of biocompatible peritoneal dialysis (PD) solutions on these levels remain to be fully defined. The present study aimed to a) evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solutions on serum lipid parameters, and b) explore the capacity of lipid parameters (total cholesterol [TC], triglyceride [TG], high density lipoprotein [HDL], TC/HDL, low density lipoprotein [LDL], very low density lipoprotein [VLDL]) to predict cardiovascular events (CVE) and mortality in PD patients. ♦ Methods: The study included 175 incident participants from the balANZ trial with at least 1 stored serum sample. A composite CVE score was used as a primary clinical outcome measure. Multilevel linear regression and Poisson regression models were fitted to describe the trend of lipid parameters over time and its ability to predict composite CVE, respectively. ♦ Results: Small but statistically significant increases in serum TG (coefficient 0.006, p < 0.001), TC/HDL (coefficient 0.004, p = 0.001), and VLDL cholesterol (coefficient 0.005, p = 0.001) levels and a decrease in the serum HDL cholesterol levels (coefficient −0.004, p = 0.009) were observed with longer time on PD, whilst the type of PD solution (biocompatible vs standard) received had no significant effect on these levels. Peritoneal dialysis glucose exposure was significantly associated with trends in TG, TC/HDL, HDL and VLDL levels. Baseline lipid parameter levels were not predictive of composite CVEs or all-cause mortality. ♦ Conclusion: Serum TG, TC/HDL, and VLDL levels increased and the serum HDL levels decreased with increasing PD duration. None of the lipid parameters were significantly modified by biocompatible PD solution use over the time period studied or predictive of composite CVE or mortality. PMID:26429421

Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

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

Li, E.J.; Cook, J.A.; Spicer, K.M.

Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change inmore » permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3.« less

Production cross sections of deuteron-induced reactions on natural palladium for Ag isotopes

NASA Astrophysics Data System (ADS)

Ukon, Naoyuki; Aikawa, Masayuki; Komori, Yukiko; Haba, Hiromitsu

2018-07-01

Activation cross sections for deuteron-induced reactions on natural palladium were measured up to 24 MeV using the stacked-foil method and the high resolution gamma-ray spectroscopy. The production cross sections of 103Ag, the parent of a medical radioactive isotope 103Pd, were obtained. We found that our result is in good agreement with the previous data up to 20.3 MeV, and obtained new data at higher energies. In addition, the production cross sections of 104g+mAg, 105Ag, 106mAg, 110mAg and 111Ag were presented.

The presence of sodium nitrate in generator eluate decreases the radiochemical purity of 99mTc-sestamibi.

PubMed

Métayé, Thierry; Rosenberg, Thierry; Guilhot, Joëlle; Bouin-Pineau, Marie-Hélène; Perdrisot, Rémy

2012-09-01

A high radiochemical purity (RCP) is recommended for radiopharmaceutical compounds used in the clinical practice of nuclear medicine. However, some preparations of (99m)Tc-sestamibi contain excess impurities (>6%). To understand the origin of these impurities, we investigated the effect of sodium nitrate on the RCP of sestamibi preparations by testing eluates from 3 commercially available (99m)Tc generators. The sestamibi kits (Stamicis) were reconstituted with (99m)Tc eluate from nitrate-containing wet-column (NCWC), nitrate-free wet-column (NFWC), and nitrate-free dry-column (NFDC) generators. Sodium nitrate was 0.05 mg/mL in eluates from the NCWC generators. The RCP was determined using aluminum oxide sheets as the stationary phase and absolute ethanol as the mobile phase. Succimer, tetrofosmin, oxidronate, exametazine, albumin nanocolloid, and soluble albumin were also tested for their RCP values with eluates from the 3 different (99m)Tc generators. The RCP assessment of (99m)Tc-sestamibi was performed on 127 Stamicis preparations. Significantly lower RCP values were found for Stamicis kits prepared with the NCWC generator than for Stamicis prepared with the NFWC (P < 0.0001) and NFDC (P < 0.0001) generators. The number of Stamicis preparations with an RCP under 94% was greater with the NCWC generator (32 of 53 kits) than with the NFDC (2 of 51 kits) or NFWC (0 of 23 kits) generator. Furthermore, the addition of a 0.05 mg/mL concentration of nitrate in NFWC generator eluates significantly decreased the RCP of the Stamicis preparation. In the absence of nitrate in (99m)Tc eluate, no difference was observed between the RCP values of Stamicis kits prepared with the NFWC and NFDC generators. The (99m)Tc impurities generated by nitrates did not modify the quality of myocardial imaging (normal heart-to-lung ratio, 2.2), probably because these impurities are not in the heart field of view. No other tested (99m)Tc-radiopharmaceutical interfered with nitrates. We recommend using nitrate-free generator eluates in (99m)Tc-sestamibi preparations to improve the product quality and prevent unnecessary exposure of the patient to radiation.

Pd nanoparticle-modified electrodes for nonenzymatic hydrogen peroxide detection

NASA Astrophysics Data System (ADS)

Wang, Jue; Chen, Xue-jiao; Liao, Kai-ming; Wang, Guang-hou; Han, Min

2015-08-01

A hydrogen peroxide (H2O2) sensor based on Pd nanoparticles (NPs) and glassy carbon electrodes (GCEs) is fabricated. Pd NPs are deposited on GCEs by using a gas phase cluster beam deposition technique. The NP-deposited electrodes show enhanced electrocatalytic activity in reduction of H2O2. The electrode with an optimized NP coverage of 85 % has a high selective and stable nonenzymatic sensing ability of H2O2 with a low detection limit (3.4 × 10-7 M), high sensitivity (50.9 μA mM-1), and a wide linear range (from 1.0 × 10-6 to 6.0 × 10-3 M). The reduction peak potential of the electrode is close to -0.12 V, which enables high selective amperometric detection of H2O2 at a low applied potential.

Variation in the Utilization of the Medicare Skilled Nursing Facility Benefit.

DTIC Science & Technology

1989-08-01

12.4 Colorado 11.8 Idaho 11.6 Florida 11.6 North Carolina 11.3 Arizona 11.3 Indiana 10.9 New Jersey 10.7 Missouri 10.7 North Dakota 10.3 Vermont 10.0...82.0 Hawaii 22.0 31.3 46.7 Idaho 0.0 5.3 94.7 Illinois 4.5 42.8 52.7 ndiana. 15.6 773 7.1 Iowa 1.8 97.1 1.1 Kansas 34 89.5 7.1 Kentucky 203 79.5 0.2...DOVER-ROCHESTER, NH-ME LAWTON, OK POUGHKEEPSIE, NY LEWISTON -AUBURN, ME PROVIDENCE, RI LEXINGTON-FAYETTE, KY PROVO-OREM, UT LIMA, OH PUEBLO, CO LINCOLN

Differential parasitological, molecular, and serological detection of Trypanosoma cruzi I, II, and IV in blood of experimentally infected mice.

PubMed

Margioto Teston, Ana Paula; Paula de Abreu, Ana; Gruendling, Ana Paula; Bahia, Maria Terezinha; Gomes, Mônica Lúcia; Marques de Araújo, Silvana; Jean de Ornelas Toledo, Max

2016-07-01

Trypanosoma cruzi is the etiological agent of American trypanosomiasis (Chagas' disease), which affects 6-7 million people worldwide, mainly in Latin America. It presents great genetic and biological variability that plays an important role in the clinical and epidemiological features of the disease. Our working hypothesis is that the genetic diversity of T. cruzi has an important impact on detection of the parasite using diagnostic techniques. The present study evaluated the diagnostic performance of parasitological, molecular, and serological techniques for detecting 27 strains of T. cruzi that belonged to discrete typing units (DTUs) TcI (11 strains), TcII (four strains), and TcIV (12 strains) that were obtained from different hosts in the states of Amazonas and Paraná, Brazil. Blood samples were taken from experimentally infected mice and analyzed by fresh blood examination, hemoculture in Liver Infusion Tryptose (LIT) medium, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA). Polymerase chain reaction presented the best detection of TcI, with 80.4% positivity. For all of the detection methods, the animals that were inoculated with TcII presented the highest positivity rates (94.1-100%). ELISA that was performed 7 months after inoculation presented a higher detection ability (95.4%) for TcIV. Intra-DTU comparisons showed that the reproducibility of the majority of the results that were obtained with the different methods was weak for TcI and good for TcII and TcIV. Our data indicate that the detection capability of different techniques varies with the DTUs of the parasites in mammalian blood. The implications of these findings with regard to the diagnosis of human T. cruzi infection are discussed. Copyright © 2016. Published by Elsevier Inc.

Effects of 99mTc-TRODAT-1 drug template on image quantitative analysis

PubMed Central

Yang, Bang-Hung; Chou, Yuan-Hwa; Wang, Shyh-Jen; Chen, Jyh-Cheng

2018-01-01

99mTc-TRODAT-1 is a type of drug that can bind to dopamine transporters in living organisms and is often used in SPCT imaging for observation of changes in the activity uptake of dopamine in the striatum. Therefore, it is currently widely used in studies on clinical diagnosis of Parkinson’s disease (PD) and movement-related disorders. In conventional 99mTc-TRODAT-1 SPECT image evaluation, visual inspection or manual selection of ROI for semiquantitative analysis is mainly used to observe and evaluate the degree of striatal defects. However, these methods are dependent on the subjective opinions of observers, which lead to human errors, have shortcomings such as long duration, increased effort, and have low reproducibility. To solve this problem, this study aimed to establish an automatic semiquantitative analytical method for 99mTc-TRODAT-1. This method combines three drug templates (one built-in SPECT template in SPM software and two self-generated MRI-based and HMPAO-based TRODAT-1 templates) for the semiquantitative analysis of the striatal phantom and clinical images. At the same time, the results of automatic analysis of the three templates were compared with results from a conventional manual analysis for examining the feasibility of automatic analysis and the effects of drug templates on automatic semiquantitative analysis results. After comparison, it was found that the MRI-based TRODAT-1 template generated from MRI images is the most suitable template for 99mTc-TRODAT-1 automatic semiquantitative analysis. PMID:29543874

Differential Lung Uptake of 99mTc-HMPAO and 99mTc-Duramycin in the Chronic Hyperoxia Rat Model

PubMed Central

Clough, Anne V.; Audi, Said H.; Haworth, Steven T.; Roerig, David L.

2015-01-01

Noninvasive radionuclide imaging has the potential to identify and assess mechanisms involved in particular stages of lung injury which occur with acute respiratory distress syndrome, for example. Lung uptake of 99mTc-hexamethylpropyleneamine oxime (HMPAO) is reported to be partially dependent on the redox status of the lung tissue while 99mTc-duramycin, a new marker of cell injury, senses cell death via apoptosis and/or necrosis. Thus, we investigated changes in lung uptake of these agents in rat exposed to hyperoxia for prolonged periods, a common model of acute lung injury. Methods Male Sprague-Dawley rats were pre-exposed to either normoxia (21% O2) or hyperoxia (85% O2) for up to 21 days. For imaging, the rats were anesthetized, injected i.v. with either 99mTc-HMPAO or 99mTc-duramycin (37-74 MBq) and planar images were acquired using a high sensitivity modular gamma camera. Subsequently, 99mTc-macroagreggated albumin (37 MBq, diam=10-40 μm) was injected i.v., imaged, and used to define a lung region-of-interest. The lung to background ratio was used as a measure of lung uptake. Results Hyperoxia exposure resulted in a 74% increase in 99mTc-HMPAO lung uptake, which peaked at 7 days and persisted for the 21 days of exposure. 99mTc-duramycin lung uptake was also maximal at 7 days of exposure but decreased to near control levels by 21 days. The sustained elevation of 99mTc-HMPAO uptake suggests ongoing changes in lung redox status whereas cell death appears to have subsided by 21 days. Conclusion These results suggest the potential use of 99mTc-HMPAO and 99mTc-duramycin as redox and cell-death imaging biomarkers, respectively, for in vivo identification and assessment of different stages of lung injury. PMID:23086010

Getters for Tc and I Removal from Liquid Waste

NASA Astrophysics Data System (ADS)

Qafoku, N. P.; Asmussen, M.; Lawter, A.; Neeway, J.; Smith, G.

2015-12-01

A cementitious waste form, Cast Stone, is being evaluated as a possible supplemental waste form for the low activity waste (LAW) at the Hanford Site, which contains significant amounts of radioactive 99Tc and 129I, as part of the tank waste cleanup mission. To improve the retention of Tc and/or I in Cast Stone, materials with a high affinity for Tc and/or I, termed "getters," can be added to decrease the rate of contaminant release and diffusivity, and improve Cast Stone performance. A series of kinetic batch sorption experiments was performed to determine the effectiveness of the getter materials. Several Tc getters [blast furnace slag, Sn (II) apatite, SnCl2, nanoporous Sn phosphate, KMS-2 (a potassium-metal-sulfide), and Sn(II) hydroxyapatite] and I getters [layered Bi hydroxide, natural argentite mineral, synthetic argentite, Ag-impregnated carbon, and Ag-exchanged zeolite] were tested in different solution media, 18.2 MΩ DI H2O and a caustic LAW waste simulant containing 6.5 M Na or 7.8 M Na. The experiments were conducted at room temperature in the presence or absence of air. Results indicated that most Tc getters (with the exception of KMS-2) performed better in the DI H2O solution than in the 6.5 and 7.8 M Na LAW simulant. In addition, Tc sequestration may be affected by the presence of other redox sensitive elements that were present in the LAW simulant, such as Cr. The Tc getter materials have been examined through various solid-state characterization techniques such as XRD, SEM/EDS, XANES and EXAFS which provided evidence for plausible mechanisms of aqueous Tc removal. The results indicated that the Tc precipitates differ depending on the getter material and that Tc(VII) is reduced to Tc(IV) in most of the getters but to a differing extents. For the I getters, Ag-exchanged zeolite and synthetic argentite were the most effective ones. The other I getters showed limited effectiveness for sorbing I under the high ionic strength and caustic conditions of the LAW simulant.

Effect of Noise in the Three-Parameter Logistic Model.

DTIC Science & Technology

1982-12-25

0 0 .0000000000000000- I C) 00000000 0 00000 虠 00 0 0000000 o0000000000000000 o 000 000000000000 0 00 0000000000000 I" ac 00000000000000 C 00 0000...r, is WwW, QD.Kvl4PdE.0 PSPSPS-4PSF) ’coo w. n. 150".-- 0-P P P. .0 PS..r4 0M4 .P ~~: p . .__ _ _ _ _ _ _ 93 Ga 4 ad43 .00 10 a, V’C VN V, :2 2~ en Ac ...00W, Mt p1-w4w. 01 V& AC NV- em, N" -n - . N . o"~ P- -.-... q" tN 4 ~ Wn - a P ’C 0,0 e0-o a ID.m %D Va-A oqr-D-a C-1 r4 P. 0% P.1v-m .D. 94 W’ 6 V

Leber's hereditary optic neuropathy (LHON)-associated ND5 12338T > C mutation altered the assembly and function of complex I, apoptosis and mitophagy.

PubMed

Zhang, Juanjuan; Ji, Yanchun; Lu, Yuanyuan; Fu, Runing; Xu, Man; Liu, Xiaoling; Guan, Min-Xin

2018-06-01

Mutations in mitochondrial DNA (mtDNA) have been associated with Leber's hereditary optic neuropathy (LHON) and their pathophysiology remains poorly understood. In this study, we demonstrated that a missense mutation (m.12338T>C, p.1M>T) in the ND5 gene contributed to the pathogenesis of LHON. The m.12338T>C mutation affected the first methionine (Met1) with a threonine and shortened two amino acids of ND5. We therefore hypothesized that the mutated ND5 perturbed the structure and function of complex I. Using the cybrid cell models, generated by fusing mtDNA-less (ρ°) cells with enucleated cells from LHON patients carrying the m.12338T>C mutation and a control subject belonging to the same mtDNA haplogroup, we demonstrated that the m.12338T>C mutation caused the reduction of ND5 polypeptide, perturbed assemble and activity of complex I. Furthermore, the m.12338T>C mutation caused respiratory deficiency, diminished mitochondrial adenosine triphosphate levels and membrane potential and increased the production of reactive oxygen species. The m.12338T>C mutation promoted apoptosis, evidenced by elevated release of cytochrome c into cytosol and increased levels of apoptosis-activated proteins: caspases 9, 3, 7 and Poly ADP ribose polymerase in the cybrids carrying the m.12338T>C mutation, as compared with control cybrids. Moreover, we also document the involvement of m.12338T>C mutation in decreased mitophagy, as showed by reduced levels of autophagy protein light chain 3 and accumulation of autophagic substrate p62 in the in mutant cybrids as compared with control cybrids. These data demonstrated the direct link between mitochondrial dysfunction caused by complex I mutation and apoptosis or mitophagy. Our findings may provide new insights into the pathophysiology of LHON.

Clinical translation of a PSMA inhibitor for 99mTc-based SPECT.

PubMed

Ferro-Flores, Guillermina; Luna-Gutiérrez, Myrna; Ocampo-García, Blanca; Santos-Cuevas, Clara; Azorín-Vega, Erika; Jiménez-Mancilla, Nallely; Orocio-Rodríguez, Emmanuel; Davanzo, Jenny; García-Pérez, Francisco O

2017-05-01

Prostate-specific membrane antigen (PSMA) is highly over-expressed in advanced prostate cancers. 68 Ga-labeled PSMA inhibitors (iPSMA) are currently used for prostate cancer detection by PET imaging. The availability of simple, efficient and reproducible radiolabeling procedures is essential for developing new SPECT radiopharmaceuticals for clinical translation. The aim of this research was to prepare 99m Tc-EDDA/HYNIC-Lys(Nal)-Urea-Glu ( 99m Tc-EDDA/HYNIC-iPSMA) obtained from lyophilized kit formulations and evaluate the in vitro and in vivo radiopharmaceutical binding to prostate cancer cells over-expressing PSMA, as well as the 99m Tc-EDDA/HYNIC-iPSMA normal biodistribution in humans and the preliminary uptake in patients with prostate cancer. 99m Tc labeling was performed by adding sodium pertechnetate solution and a 0.2M phosphate buffer (pH 7.0) to a lyophilized formulation containing HYNIC-iPSMA, EDDA, tricine, mannitol and stannous chloride. The radiochemical purity was evaluated by reversed-phase HPLC and ITLC-SG analyses. Stability studies in human serum were performed by size-exclusion HPLC. In vitro cell uptake was tested using prostate cancer cells (LNCaP) with blocked and non-blocked receptors. Biodistribution and tumor uptake were determined in LNCaP tumor-bearing nude mice with blocked and non-blocked receptors, and images were obtained using a micro-SPECT/CT. Whole-body images from three healthy men and two patients with histologically-confirmed prostate cancer (one of them with a previous 68 Ga-PSMA-617scan) were acquired at 1h and 3h after 99m Tc-EDDA/HYNIC-iPSMA administration with radiochemical purities of >98%. In vitro and in vivo studies showed high radiopharmaceutical stability in human serum, specific recognition for PSMA, high tumor uptake (10.22±2.96% ID/g at 1h) with rapid blood clearance and mainly kidney elimination. Preliminary images in patients demonstrated the ability of 99m Tc-EDDA/HYNIC-iPSMA to detect tumors and metastases of prostate cancer as well as 68 Ga-PSMA-617 does. The results obtained in this study warrant further dosimetry and clinical studies to determine the specificity and sensitivity of 99m Tc-EDDA/HYNIC-iPSMA. Copyright © 2017 Elsevier Inc. All rights reserved.

α-Synuclein stimulation of monoamine oxidase-B and legumain protease mediates the pathology of Parkinson's disease.

PubMed

Kang, Seong Su; Ahn, Eun Hee; Zhang, Zhentao; Liu, Xia; Manfredsson, Fredric P; Sandoval, Ivette M; Dhakal, Susov; Iuvone, P Michael; Cao, Xuebing; Ye, Keqiang

2018-06-15

Dopaminergic neurodegeneration in Parkinson's disease (PD) is associated with abnormal dopamine metabolism by MAO-B (monoamine oxidase-B) and intracellular α-Synuclein (α-Syn) aggregates, called the Lewy body. However, the molecular relationship between α-Syn and MAO-B remains unclear. Here, we show that α-Syn directly binds to MAO-B and stimulates its enzymatic activity, which triggers AEP (asparagine endopeptidase; legumain) activation and subsequent α-Syn cleavage at N103, leading to dopaminergic neurodegeneration. Interestingly, the dopamine metabolite, DOPAL, strongly activates AEP, and the N103 fragment of α-Syn binds and activates MAO-B. Accordingly, overexpression of AEP in SNCA transgenic mice elicits α-Syn N103 cleavage and accelerates PD pathogenesis, and inhibition of MAO-B by Rasagiline diminishes α-Syn-mediated PD pathology and motor dysfunction. Moreover, virally mediated expression of α-Syn N103 induces PD pathogenesis in wild-type, but not MAO-B-null mice. Our findings thus support that AEP-mediated cleavage of α-Syn at N103 is required for the association and activation of MAO-B, mediating PD pathogenesis. © 2018 The Authors.

99mTc-HYNIC-(tricine/EDDA)-FROP peptide for MCF-7 breast tumor targeting and imaging.

PubMed

Ahmadpour, Sajjad; Noaparast, Zohreh; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

2018-02-19

Breast cancer is the most common malignancy among women in the world. Development of novel tumor-specific radiopharmaceuticals for early breast tumor diagnosis is highly desirable. In this study we developed 99m Tc-HYNIC-(tricine/EDDA)-Lys-FROP peptide with the ability of specific binding to MCF-7 breast tumor. The FROP-1 peptide was conjugated with the bifunctional chelator hydrazinonicotinamide (HYNIC) and labeled with 99m Tc using tricine/EDDA co-ligand. The cellular specific binding of 99m Tc-HYNIC-FROP was evaluated on different cell lines as well as with blocking experiment on MCF-7 (human breast adenocarcinoma). The tumor targeting and imaging of this labeled peptide were performed on MCF-7 tumor bearing mice. Radiochemical purity for 99m Tc-HYNIC-(tricine/EDDA)-FROP was 99% which was determined with ITLC method. This radiolabeled peptide showed high stability in normal saline and serum about 98% which was monitored with HPLC method. In saturation binding experiments, the binding constant (K d ) to MCF-7 cells was determined to be 158 nM. Biodistribution results revealed that the 99m Tc-HYNIC-FROP was mainly exerted from urinary route. The maximum tumor uptake was found after 30 min post injection (p.i.); however maximum tumor/muscle ratio was seen at 15 min p.i. The tumor uptake of this labeled peptide was specific and blocked by co-injection of excess FROP. According to the planar gamma imaging result, tumor was clearly visible due to the tumor uptake of 99m Tc-HYNIC-(tricine/EDDA)-FROP in mouse after 15 min p.i. The 99m Tc-HYNIC-(tricine/EDDA)-FROP is considered a promising probe with high specific binding to MCF-7 breast cancer cells.

Effect of pH in a Pd-based ethanol membraneless air breathing nanofluidic fuel cell with flow-through electrodes

NASA Astrophysics Data System (ADS)

López-Rico, C. A.; Galindo-de-la-Rosa, J.; Ledesma-García, J.; Arriaga, L. G.; Guerra-Balcázar, M.; Arjona, N.

2015-12-01

In this work, a nanofluidic fuel cell (NFC) in which streams flow through electrodes was used to investigate the role of pH in the cell performance using ethanol as fuel and two Pd nanoparticles as electrocatalysts: one commercially available (Pd/C from ETEK) and other synthesized using ionic liquids (Pd/C IL). The cell performances for both electrocatalysts in acid/acid (anodic/cathodic) streams were of 18.05 and 9.55 mW cm-2 for Pd/C ETEK and Pd/C IL. In alkaline/alkaline streams, decrease to 15.94 mW cm-2 for Pd/C ETEK and increase to 15.37 mW cm-2 for Pd/C IL. In alkaline/acidic streams both electrocatalysts showed similar cell voltages (up to 1 V); meanwhile power densities were of 87.6 and 99.4 mW cm-2 for Pd/C ETEK and Pd/C IL. The raise in cell performance can be related to a decrease in activation losses, the combined used of alkaline and acidic streams and these high values compared with flow-over fuel cells can be related to the enhancement of the cathodic mass transport by using three dimensional porous electrodes and two sources of oxygen: from air and from a saturated solution.

Radiopharmaceuticals for SPECT cancer detection

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

Chernov, V. I., E-mail: chernov@oncology.tomsk.ru; Medvedeva, A. A., E-mail: tickayaAA@oncology.tomsk.ru; Zelchan, R. V., E-mail: r.zelchan@yandex.ru

2016-08-02

The purpose of the study was to assess the efficacy of single photon emission computed tomography (SPECT) with {sup 199}Tl and {sup 99}mTc-MIBI in the detection of breast, laryngeal and hypopharyngeal cancers. A total of 220 patients were included into the study: 120 patients with breast lesions (100 patients with breast cancer and 20 patients with benign breast tumors) and 100 patients with laryngeal/hypopharyngeal diseases (80 patients with laryngeal/hypopharyngeal cancer and 20 patients with benign laryngeal/hypopharyngeal lesions). No abnormal {sup 199}Tl uptake was seen in all patients with benign breast and laryngeal lesions, indicating a 100% specificity of {sup 199}Tlmore » SPECT. In the breast cancer patients, the increased {sup 199}Tl uptake in the breast was visualized in 94.8% patients, {sup 99m}Tc-MIBI—in 93.4% patients. The increased {sup 199}Tl uptake in axillary lymph nodes was detected in 60% patients, and {sup 99m}Tc-MIBI—in 93.1% patients. In patients with laryngeal/hypopharyngeal cancer, the sensitivity of SPECT with {sup 199}Tl and {sup 99m}Tc-MIBI was 95%. The {sup 199}Tl SPECT sensitivity in identification of regional lymph node metastases in the patients with laryngeal/hypopharyngeal cancer was 75% and the {sup 99m}Tc-MIBI SPECT sensitivity was 17%. The data obtained showed that SPECT with {sup 199}Tl and {sup 99m}Tc-MIBI can be used as one of the additional imaging methods in detection of tumors.« less

Reactive glia promote development of CD103+ CD69+ CD8+ T-cells through programmed cell death-ligand 1 (PD-L1).

PubMed

Prasad, Sujata; Hu, Shuxian; Sheng, Wen S; Chauhan, Priyanka; Lokensgard, James R

2018-06-01

Previous work from our laboratory has demonstrated in vivo persistence of CD103 + CD69 + brain resident memory CD8 + T-cells (bT RM ) following viral infection, and that the PD-1: PD-L1 pathway promotes development of these T RM cells within the brain. Although glial cells express low basal levels of PD-L1, its expression is upregulated upon IFN-γ-treatment, and they have been shown to modulate antiviral T-cell effector responses through the PD-1: PD-L1 pathway. We performed flow cytometric analysis of cells from co-cultures of mixed glia and CD8 + T-cells obtained from wild type mice to investigate the role of glial cells in the development of bT RM . In this study, we show that interactions between reactive glia and anti-CD3 Ab-stimulated CD8 + T-cells promote development of CD103 + CD69 + CD8 + T-cells through engagement of the PD-1: PD-L1 pathway. These studies used co-cultures of primary murine glial cells obtained from WT animals along with CD8 + T-cells obtained from either WT or PD-1 KO mice. We found that αCD3 Ab-stimulated CD8 + T-cells from WT animals increased expression of CD103 and CD69 when co-cultured with primary murine glial cells. In contrast, significantly reduced expression of CD103 and CD69 was observed using CD8 + T-cells from PD-1 KO mice. We also observed that reactive glia promoted high levels of CD127, a marker of memory precursor effector cells (MPEC), on CD69 + CD8 + T-cells, which promotes development of T RM cells. Interestingly, results obtained using T-cells from PD-1 KO animals showed significantly reduced expression of CD127 on CD69 + CD8 + cells. Additionally, blocking of glial PD-L1 resulted in decreased expression of CD103, along with reduced CD127 on CD69 + CD8 + T-cells. Taken together, these results demonstrate a role for activated glia in promoting development of bT RM through the PD-1: PD-L1 pathway. © 2018 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

CePd2Ga3 and CePd2Zn3 - Kondo lattices and magnetic behaviour

NASA Astrophysics Data System (ADS)

Bartha, A.; Vališka, M.; Míšek, M.; Proschek, P.; Kaštil, J.; Dušek, M.; Sechovský, V.; Prokleška, J.

2018-05-01

We report the single crystal properties of CePd2Zn3 and CePd2Ga3 compounds. The compounds were prepared by Bridgman method in high-frequency induction furnace. Both compounds adopt the hexagonal PrNi2Al3-type structure with a = 5.3914(2) Å, c = 4.3012(2) Å for CePd2Zn3 and a = 5.4106(8) Å, c = 4.2671(8) Å for CePd2Ga3, respectively. CePd2Zn3 orders antiferromagnetically below TN = 1.9 K. Magnetoresistance measurements revealed a crossover at Bc = 0.95 T. CePd2Ga3 orders ferromagnetically at TC = 6.7 K. Applied hydrostatic pressure reduces the value of the Curie-temperature (rate ∂TC / ∂ p = 0.9 K GPa -1) down to 3.9 K at 3.2 GPa. Both compounds display a strong magnetocrystalline anisotropy with easy axis of magnetization perpendicular to the c-axis in the hexagonal lattice.

Importance of the van Hove singularity in superconducting PdTe2

NASA Astrophysics Data System (ADS)

Kim, Kyoo; Kim, Sooran; Kim, J. S.; Kim, Heejung; Park, J.-H.; Min, B. I.

2018-04-01

We have investigated the electronic, phononic, and superconducting properties of the transition-metal dichalcogenide superconductor PdTe2, and explored the origin of different superconducting behaviors between PdTe2 and its isostructural PtTe2 that is nonsuperconducting. We have found that the saddle-point van Hove singularity (vHs) near the Fermi level, which interacts strongly with Te phonon modes, plays an important role in the BCS-type superconductivity of PdTe2. We show that, with electron doping, the vHs in PdTe2 shifts down toward the Fermi level to enhance Tc, as is consistent with the observed enhancement of Tc in Cu-doped PdTe2. We ascribe the absence of superconductivity in PtTe2 to the different dispersion behavior of the saddle-point vHs band from that of PdTe2. We also suggest that this difference in the vHs band behaviors is responsible for the different structural responses of PdTe2 and PtTe2 to external pressure.

USSR Report, Space Biology and Aerospace Medicine, Vol. 18, No. 3, May-June 1984

DTIC Science & Technology

1984-07-03

high altitude. In the Khan Tengri expedition (6996 m), the climbers took 3-4 ordinary multiple vitamin lozenges per day during the stay in the... Tengri , only 2 of the 20 climbers who reached the top presented distinct signs of mountain sickness (apathy, muscular weakness, impaired...min/kg 4,5±0,2 3,9±0,3 (3,6—4,9) (2,96-4,8) % ECFV/min 1,34±0,I1 1,18±0,14* (1,09—1,59) (0,8—1,5) BPS 124±6 167±5* (103— 137 ) (153—187) BPd 81 ±4

KSC-08pd1714

NASA Image and Video Library

2008-06-14

CAPE CANAVERAL, Fla. – After their successful STS-124 mission and landing on Runway 15 at NASA's Kennedy Space Center, crew members exit the crew transport vehicle. Leading the way is Commander Mark Kelly, followed by (from left) Mission Specialists Mike Fossum, Karen Nyberg, Akihiko Hoshide and Ron Garan. Behind them is Stephen Lindsay, chief of the Astronaut Corps, and astronaut Janet Kavandi. Space shuttle Discovery's main landing gear touched down at 11:15:19 a.m. EDT on Runway 15. The nose landing gear touched down at 11:15:30 a.m. and wheel stop was at 11:16:19 a.m. The mission completed 5.7 million miles. The STS-124 mission delivered the Japan Aerospace Exploration Agency's large Japanese Pressurized Module and its remote manipulator system to the space station. Photo credit: NASA/Kim Shiflett

Pharmacokinetics and pharmacodynamics of levofloxacin injection in healthy Chinese volunteers and dosing regimen optimization

PubMed Central

Cao, G; Zhang, J; Wu, X; Yu, J; Chen, Y; Ye, X; Zhu, D; Zhang, Y; Guo, B; Shi, Y

2013-01-01

What is known and objective The pharmacokinetics (PK) and pharmacodynamics (PD) of levofloxacin were investigated following administration of levofloxacin injection in healthy Chinese volunteers for optimizing dosing regimen. Methods The PK study included single-dose (750 mg/150 mL) and multiple-dose (750 mg/150 mL once daily for 7 days) phases. The concentration of levofloxacin in blood and urine was determined using HPLC method. Both non-compartmental and compartmental analyses were performed to estimate PK parameters. Taking fCmax/MIC ≥5 and fAUC24 h/MIC ≥30 as a target, the cumulative fraction of response (CFR) of levofloxacin 750 mg for treatment of community-acquired pneumonia (CAP) was calculated using Monte Carlo simulation. The probability of target attainment (PTA) of levofloxacin at various minimal inhibitory concentrations (MICs) was also evaluated. Results and discussion The results of PK study showed that the Cmax and AUC0–∞ of levofloxacin were 14·94 μg/mL and 80·14 μg h/mL following single-dose infusion of levofloxacin. The half-life and average cumulative urine excretion ratio within 72 h post-dosing were 7·75 h and 86·95%, respectively. The mean Css,max, Css,min and AUC0–τ of levofloxacin at steady state following multiple doses were 13·31 μg/mL, 0·031 μg/mL and 103·7 μg h/mL, respectively. The accumulation coefficient was 1·22. PK/PD analysis revealed that the CFR value of levofloxacin 750-mg regimen against Streptococcus pneumoniae was 96·2% and 95·4%, respectively, in terms of fCmax/MIC and fAUC/MIC targets. What is new and conclusion The regimen of 750-mg levofloxacin once daily provides a satisfactory PK/PD profile against the main pathogenic bacteria of CAP, which implies promising clinical and bacteriological efficacy for patients with CAP. A large-scale clinical study is warranted to confirm these results. PMID:23701411

Pharmacokinetics and pharmacodynamics of levofloxacin injection in healthy Chinese volunteers and dosing regimen optimization.

PubMed

Cao, G; Zhang, J; Wu, X; Yu, J; Chen, Y; Ye, X; Zhu, D; Zhang, Y; Guo, B; Shi, Y

2013-10-01

The pharmacokinetics (PK) and pharmacodynamics (PD) of levofloxacin were investigated following administration of levofloxacin injection in healthy Chinese volunteers for optimizing dosing regimen. The PK study included single-dose (750 mg/150 mL) and multiple-dose (750 mg/150 mL once daily for 7 days) phases. The concentration of levofloxacin in blood and urine was determined using HPLC method. Both non-compartmental and compartmental analyses were performed to estimate PK parameters. Taking fC(max) /MIC ≥5 and fAUC(24 h) /MIC ≥30 as a target, the cumulative fraction of response (CFR) of levofloxacin 750 mg for treatment of community-acquired pneumonia (CAP) was calculated using Monte Carlo simulation. The probability of target attainment (PTA) of levofloxacin at various minimal inhibitory concentrations (MICs) was also evaluated. The results of PK study showed that the C(max) and AUC(0-∞) of levofloxacin were 14·94 μg/mL and 80·14 μg h/mL following single-dose infusion of levofloxacin. The half-life and average cumulative urine excretion ratio within 72 h post-dosing were 7·75 h and 86·95%, respectively. The mean C(ss,max), C(ss,min) and AUC(0-τ) of levofloxacin at steady state following multiple doses were 13·31 μg/mL, 0·031 μg/mL and 103·7 μg h/mL, respectively. The accumulation coefficient was 1·22. PK/PD analysis revealed that the CFR value of levofloxacin 750-mg regimen against Streptococcus pneumoniae was 96·2% and 95·4%, respectively, in terms of fC(max) /MIC and fAUC/MIC targets. The regimen of 750-mg levofloxacin once daily provides a satisfactory PK/PD profile against the main pathogenic bacteria of CAP, which implies promising clinical and bacteriological efficacy for patients with CAP. A large-scale clinical study is warranted to confirm these results. © 2013 John Wiley & Sons Ltd.

99mTc-zolmitriptan: radiolabeling, molecular modeling, biodistribution and gamma scintigraphy as a hopeful radiopharmaceutical for lung nuclear imaging.

PubMed

Rashed, H M; Marzook, F A; Farag, H

2016-12-01

Lung imaging radiopharmaceuticals are helpful agents for measuring pulmonary blood flow and allow detection of pulmonary embolism and lung cancer. The goal of this study was to develop a novel potential radiopharmaceutical for lung imaging. Zolmitriptan (a selective serotonin receptor agonist) was successfully labeled with 99m Tc via direct labeling method under reductive conditions studying different factors affecting the labeling efficiency. 99m Tc-zolmitriptan was obtained with a maximum labeling yield of 92.5 ± 0.61 % and in vitro stability up to 24 h. Molecular modeling was done to predict the structure of 99m Tc-zolmitriptan and ensure that radiolabeling did not affect binding ability of zolmitriptan to its receptor. Biodistribution studies showed that maximum lung uptake of 99m Tc-zolmitriptan was 23.89 ± 1.2 % injected dose/g tissue at 15 min post-injection and retention in lungs remained high up to 1 h, whereas the clearance from mice appeared to proceed mainly via the renal pathway. Scintigraphic images confirmed the biodistribution results showing a high resolution lung image with low accumulation of radioactivity in other organs except kidneys and urinary bladder. 99m Tc-zolmitriptan is not a blood product and so it is more safe than the currently available 99m Tc-MAA, and its lung uptake is higher than that of the recently discovered 123 I-IPMPD, 99m Tc(CO) 5 I and 99m Tc-DHPM. So, 99m Tc-zolmitriptan could be used as a hopeful radiopharmaceutical for lung scintigraphic imaging.

Calculation of therapeutic activity of radioiodine in Graves' disease by means of Marinelli's formula, using technetium (99mTc) scintigraphy.

PubMed

Szumowski, Piotr; Mojsak, Małgorzata; Abdelrazek, Saeid; Sykała, Monika; Amelian-Fiłonowicz, Anna; Jurgilewicz, Dorota; Myśliwiec, Janusz

2016-12-01

The therapeutic activity of 131 I administered to patients with Graves' disease can be calculated by means of Marinelli's formula. The thyroidal iodine uptake ( 131 IU max ) needed for the calculation is usually determined with the use of 131 I. The purpose of the paper was to estimate 131 IU max on the basis of technetium uptake in the thyroid at 20 min ( 99m TcU 20min ). Eighty patients suffering from Graves' disease were qualified for radioiodine therapy with measurement of fT 4 , fT 3 , thyroid-stimulating hormone and its receptor (TRAb). Prior to the treatment, all the patients were euthyroid. 131 IU max for each patient was determined according to the levels of 131 I after 24 h ( 131 IU 24h ), while effective half-life (T eff ) according to the measurements of 131 IU 24h and 131 I uptake after 48 h ( 131 IU 48h ). Additionally, on the day before measuring 131 IU 24h , 99m TcU 20min was calculated for each patient. It was demonstrated that there existed a correlation, with statistical significance at p < 0.05, between the following pairs of values: TRAb and 131 IU 24h , TRAb and 99m TcU 20min , and 99m TcU 20min and 131 IU 24h . The interdependence between 131 IU 24h and 99m TcU 20min at the level of significance p < 0.05 is described by the following algorithms: 131 IU 24h  = 17.72 × ln ( 99m TcU 20min ) + 30.485, if TRAb < 10 IU/ml, and 131 IU 24h  = 18.03 × ln ( 99m TcU 20min ) + 38.726, if TRAb > 10 IU/ml. It is possible to predict thyroid iodine uptake 131 IU 24h in Graves' disease on the basis of measuring the uptake of 99m TcU 20min . This shortens the time necessary for diagnosis and enables the calculation of 131 I activity using Marinelli's formula.

Programmed cell death 1 (PD-1) regulates the effector function of CD8 T cells via PD-L1 expressed on target keratinocytes.

PubMed

Okiyama, Naoko; Katz, Stephen I

2014-09-01

Programmed cell death 1 (PD-1) is an inhibitory molecule expressed by activated T cells. Its ligands (PD-L1 and -L2; PD-Ls) are expressed not only by a variety of leukocytes but also by stromal cells. To assess the role of PD-1 in CD8 T cell-mediated diseases, we used PD-1-knockout (KO) OVA-specific T cell-receptor transgenic (Tg) CD8 T cells (OT-I cells) in a murine model of mucocutaneous graft-versus-host disease (GVHD). We found that mice expressing OVA on epidermal keratinocytes (K14-mOVA mice) developed markedly enhanced GVHD-like disease after transfer of PD-1-KO OT-I cells as compared to those mice transferred with wild-type OT-I cells. In addition, K14-mOVA × OT-I double Tg (DTg) mice do not develop GVHD-like disease after adoptive transfer of OT-I cells, while transfer of PD-1-KO OT-I cells caused GVHD-like disease in a Fas/Fas-L independent manner. These results suggest that PD-1/PD-Ls-interactions have stronger inhibitory effects on pathogenic CD8 T cells than does Fas/Fas-L-interactions. Keratinocytes from K14-mOVA mice with GVHD-like skin lesions express PD-L1, while those from mice without the disease do not. These findings reflect the fact that primary keratinocytes express PD-L1 when stimulated by interferon-γ in vitro. When co-cultured with K14-mOVA keratinocytes for 2 days, PD-1-KO OT-I cells exhibited enhanced proliferation and activation compared to wild-type OT-I cells. In addition, knockdown of 50% PD-L1 expression on the keratinocytes with transfection of PD-L1-siRNA enhanced OT-I cell proliferation. In aggregate, our data strongly suggest that PD-L1, expressed on activated target keratinocytes presenting autoantigens, regulates autoaggressive CD8 T cells, and inhibits the development of mucocutaneous autoimmune diseases. Published by Elsevier Ltd.

Simulating Rule-Based Systems

DTIC Science & Technology

1988-12-01

the number of facts. NFIRE : location of the rule status flag. NLVL: the number of levels. NRULE: the number of rules. 116 NRUN: the number of runs. PD...C-INITIALIZE THE RULE MATRIX 124 C NFIRE -4 +MAXL+MAXR NFAC-0 IL-MAXL-MINL+l IR-MAXR-MINR+ 1 DO 10 I-1,NRULE MR(I,1)=I NR( I, 2)-MINL+INT(RAN( II) *IL...NR( I, 3)-MINR+INT(RAN(II)*IR) NR( I, NFIRE )-0 10 CONTINUE-A C C-STORE THE RANDOM-ASSERTION SET IN A MATRIX C READ(8,* )NRUN, lASS DO 120 I-1,NRTJN

Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients.

PubMed

Rojkó, Lívia; Reiniger, Lilla; Téglási, Vanda; Fábián, Katalin; Pipek, Orsolya; Vágvölgyi, Attila; Agócs, László; Fillinger, János; Kajdácsi, Zita; Tímár, József; Döme, Balázs; Szállási, Zoltán; Moldvay, Judit

2018-04-19

While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression is unknown. The aim of this study was to determine the changes in PD-L1 expression of tumor cells (TC) and immune cells (IC), in PD-1 expression of IC, and in the amount of stromal mononuclear cell infiltration after platinum-based chemotherapy in patients with lung cancer. We determined the amount of stromal mononuclear cells and PD-L1/PD-1 expressions by immunohistochemistry in bronchoscopic biopsy samples including 20 adenocarcinomas (ADC), 15 squamous cell carcinomas (SCC), 2 other types of non-small cell lung cancer, and 4 small cell lung cancers together with their corresponding surgical resection tissues after platinum-based chemotherapy. PD-L1 expression of TC decreased in ten patients (24.4%) and increased in three patients (7.32%) after neoadjuvant chemotherapy (p = 0.051). The decrease in PD-L1 expression, however, was significant only in patients who received cisplatin-gemcitabine combination (p = 0.020), while in the carboplatin-paclitaxel group, no similar tendency could be observed (p = 0.432). There was no difference between ADC and SCC groups. Neither PD-1 expression nor the amount of stromal IC infiltration showed significant changes after chemotherapy. This is the first study, in which both PD-L1 and PD-1 expression were analyzed together with the amount of stromal IC infiltration in different histological subtypes of lung cancer before and after platinum-based chemotherapy. Our results confirm that chemotherapy decreases PD-L1 expression of TC in a subset of patients, therefore, rebiopsy and re-evaluation of PD-L1 expression may be necessary for the indication of immune checkpoint inhibitor therapy.

Differences in the intracellular processing of the radiolabel following the uptake of iodine-125- and technetium-99m-neogalactosyl albumin by the isolated perfused rat liver

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

Gore, S.; Morris, A.I.; Gilmore, I.T.

1991-03-01

Neogalactosyl albumin (NGA) is a synthetic ligand to the asialoglycoprotein receptor (hepatic binding protein), which has been proposed as a useful receptor binding radiopharmaceutical for the noninvasive assessment of liver function. We have compared the uptake and intracellular processing of iodine-125- (125I) and technetium-99m- ({sup 99m}Tc) NGA following its administration as a 1-min pulse (147 pmol) to the isolated perfused rat liver. Approximately 40% of a pulse of either {sup 125}I- or {sup 99m}Tc-NGA were taken up first pass by the liver. Of the {sup 125}I taken up by the liver, 82% was released after 15-20 min at the sinusoidalmore » pole of the hepatocyte, predominantly as small molecular weight metabolites. A further 8% of the {sup 125}I-associated radioactivity was secreted as intact NGA into bile by the non-lysosomal (direct) pathway while 6% remained in the liver 1 hr after the pulse. In contrast, of the {sup 99m}Tc taken up by the liver, only 4% reappeared in the perfusate while 40% was secreted into bile by the lysosomal (indirect) pathway and 55% remained in the liver 1 hr after the pulse. Since labeled metabolites of {sup 99m}Tc-NGA do not appear in plasma, this permits kinetic modeling with {sup 99m}Tc-NGA without correction for labeled metabolites. Thus, {sup 99m}Tc-NGA is an excellent candidate as a receptor-binding radiopharmaceutical.« less

Cluster pattern analysis of energy deposition sites for the brachytherapy sources 103Pd, 125I, 192Ir, 137Cs, and 60Co.

PubMed

Villegas, Fernanda; Tilly, Nina; Bäckström, Gloria; Ahnesjö, Anders

2014-09-21

Analysing the pattern of energy depositions may help elucidate differences in the severity of radiation-induced DNA strand breakage for different radiation qualities. It is often claimed that energy deposition (ED) sites from photon radiation form a uniform random pattern, but there is indication of differences in RBE values among different photon sources used in brachytherapy. The aim of this work is to analyse the spatial patterns of EDs from 103Pd, 125I, 192Ir, 137Cs sources commonly used in brachytherapy and a 60Co source as a reference radiation. The results suggest that there is both a non-uniform and a uniform random component to the frequency distribution of distances to the nearest neighbour ED. The closest neighbouring EDs show high spatial correlation for all investigated radiation qualities, whilst the uniform random component dominates for neighbours with longer distances for the three higher mean photon energy sources (192Ir, 137Cs, and 60Co). The two lower energy photon emitters (103Pd and 125I) present a very small uniform random component. The ratio of frequencies of clusters with respect to 60Co differs up to 15% for the lower energy sources and less than 2% for the higher energy sources when the maximum distance between each pair of EDs is 2 nm. At distances relevant to DNA damage, cluster patterns can be differentiated between the lower and higher energy sources. This may be part of the explanation to the reported difference in RBE values with initial DSB yields as an endpoint for these brachytherapy sources.

Comparison of TG‐43 dosimetric parameters of brachytherapy sources obtained by three different versions of MCNP codes

PubMed Central

Zaker, Neda; Sina, Sedigheh; Koontz, Craig; Meigooni1, Ali S.

2016-01-01

Monte Carlo simulations are widely used for calculation of the dosimetric parameters of brachytherapy sources. MCNP4C2, MCNP5, MCNPX, EGS4, EGSnrc, PTRAN, and GEANT4 are among the most commonly used codes in this field. Each of these codes utilizes a cross‐sectional library for the purpose of simulating different elements and materials with complex chemical compositions. The accuracies of the final outcomes of these simulations are very sensitive to the accuracies of the cross‐sectional libraries. Several investigators have shown that inaccuracies of some of the cross section files have led to errors in  125I and  103Pd parameters. The purpose of this study is to compare the dosimetric parameters of sample brachytherapy sources, calculated with three different versions of the MCNP code — MCNP4C, MCNP5, and MCNPX. In these simulations for each source type, the source and phantom geometries, as well as the number of the photons, were kept identical, thus eliminating the possible uncertainties. The results of these investigations indicate that for low‐energy sources such as  125I and  103Pd there are discrepancies in gL(r) values. Discrepancies up to 21.7% and 28% are observed between MCNP4C and other codes at a distance of 6 cm for  103Pd and 10 cm for  125I from the source, respectively. However, for higher energy sources, the discrepancies in gL(r) values are less than 1.1% for  192Ir and less than 1.2% for  137Cs between the three codes. PACS number(s): 87.56.bg PMID:27074460

Modified COMS Plaques for {sup 125}I and {sup 103}Pd Iris Melanoma Brachytherapy

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

Thomson, Rowan M., E-mail: rthomson@physics.carleton.c; Furutani, Keith M.; Pulido, Jose S.

2010-11-15

Purpose: Novel plaques are used to treat iris melanoma at the Mayo Clinic Rochester. The plaques are a modification of the Collaborative Ocular Melanoma Study (COMS) 22 mm plaque design with a gold alloy backing, outer lip, and silicone polymer insert. An inner lip surrounds a 10 mm diameter cutout region at the plaque center. Plaques span 360{sup o}, 270{sup o}, and 180{sup o} arcs. This article describes dosimetry for these plaques and others used in the treatment of anterior eye melanomas. Methods and Materials: The EGSnrc user-code BrachyDose is used to perform Monte Carlo simulations. Plaques and seeds aremore » fully modeled. Three-dimensional dose distributions for different plaque models, TG-43 calculations, and {sup 125}I (model 6711) and {sup 103}Pd (model 200) seeds are compared via depth-dose curves, tabulation of doses at points of interest, and isodose contours. Results: Doses at points of interest differ by up to 70% from TG-43 calculations. The inner lip reduces corneal doses. Matching plaque arc length to tumor extent reduces doses to eye regions outside the treatment area. Maintaining the same prescription dose, {sup 103}Pd offers lower doses to critical structures than {sup 125}I, with the exception of the sclera adjacent to the plaque. Conclusion: The Mayo Clinic plaques offer several advantages for anterior eye tumor treatments. Doses to regions outside the treatment area are significantly reduced. Doses differ considerably from TG-43 predictions, illustrating the importance of complete Monte Carlo simulations. Calculations take a few minutes on a single CPU, making BrachyDose sufficiently fast for routine clinical treatment planning.« less

Cluster pattern analysis of energy deposition sites for the brachytherapy sources 103Pd, 125I, 192Ir, 137Cs, and 60Co

NASA Astrophysics Data System (ADS)

Villegas, Fernanda; Tilly, Nina; Bäckström, Gloria; Ahnesjö, Anders

2014-09-01

Analysing the pattern of energy depositions may help elucidate differences in the severity of radiation-induced DNA strand breakage for different radiation qualities. It is often claimed that energy deposition (ED) sites from photon radiation form a uniform random pattern, but there is indication of differences in RBE values among different photon sources used in brachytherapy. The aim of this work is to analyse the spatial patterns of EDs from 103Pd, 125I, 192Ir, 137Cs sources commonly used in brachytherapy and a 60Co source as a reference radiation. The results suggest that there is both a non-uniform and a uniform random component to the frequency distribution of distances to the nearest neighbour ED. The closest neighbouring EDs show high spatial correlation for all investigated radiation qualities, whilst the uniform random component dominates for neighbours with longer distances for the three higher mean photon energy sources (192Ir, 137Cs, and 60Co). The two lower energy photon emitters (103Pd and 125I) present a very small uniform random component. The ratio of frequencies of clusters with respect to 60Co differs up to 15% for the lower energy sources and less than 2% for the higher energy sources when the maximum distance between each pair of EDs is 2 nm. At distances relevant to DNA damage, cluster patterns can be differentiated between the lower and higher energy sources. This may be part of the explanation to the reported difference in RBE values with initial DSB yields as an endpoint for these brachytherapy sources.

National cyclotron centre at the Institute for Nuclear Research and Nuclear Energy

NASA Astrophysics Data System (ADS)

Tonev, D.; Goutev, N.; Asova, G.; Artinyan, A.; Demerdjiev, A.; Georgiev, L. S.; Yavahchova, M.; Bashev, V.; Genchev, S. G.; Geleva, E.; Mincheva, M.; Nikolov, A.; Dimitrov, D. T.

2018-05-01

An accelerator laboratory is presently under construction in Sofia at the Institute for Nuclear Research and Nuclear Energy. The laboratory will use a TR24 type of cyclotron, which provides a possibility to accelerate a proton beam with an energy of 15 to 24 MeV and current of up to 0.4 mA. An accelerator with such parameters allows to produce a large variety of radioisotopes for development of radiopharmaceuticals. The most common radioisotopes that can be produced with such a cyclotron are PET isotopes like: 11C, 13N, 15O, 18F, 124I, 64Cu, 68Ge/68Ga, and SPECT isotopes like: 123I, 111In, 67Ga, 57Co, 99mTc. Our aim is to use the cyclotron facility for research in the fields of radiopharmacy, radiochemistry, radiobiology, nuclear physics, materials sciences, applied research, new materials and for education in all these fields including nuclear energy. Presently we perform investigations in the fields of target design for production of radioisotopes, shielding and radioprotection, new ion sources etc.

[Inferior frontal region hypoperfusion in Parkinson disease with dementia].

PubMed

Ochudło, Stanisław; Opala, Grzegorz; Jasińska-Myga, Barbara; Siuda, Joanna; Nowak, Stanisław

2003-01-01

Dementia is more frequent in patients suffering from Parkinson's disease (PD) then in general population. The mechanism for mental deterioration in PD remains controversial. The aim of our study was comparison of the regional cerebral perfusion quantified by single photon emission computed tomography in patients suffering from idiopathic Parkinson's disease with and without dementia. We examined 49 PD patients: 22 PD patients with dementia and 27 PD patients without dementia. Dementia was recognized according to ICD-10 and DSM-IV criteria. Cognitive functions were executed by means of the Mini Mental State Examination (MMSE) and neuropsychological assessment. The Unified Parkinson's Disease Rating Scale (UPDRS) and Modified Hoehn & Yahr Scale was used to quantify the severity of PD. SPECT was performed with Siemens Diacam single--head rotating gamma camera after intravenous application of technetium 99m hexamethylpropylene amine oxime (99mTc-HMPAO). The perfusion values were expressed as cortical or basal ganglia regions of interest (ROIs)/cerebellum activity ratios. In both examined group of patients the lowest uptake was in basal ganglia region, while the highest uptake was in occipital region. In the subgroup of PD patients with dementia significant hypoperfusion affecting the inferior frontal cortices was observed. In Parkinson's disease with dementia hypoperfusion in inferior frontal region can be found.

KSC-08pd1174

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Akihiko Hoshide takes his place in the M113 armored personnel carrier, to practice driving as part of emergency training. He and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1171

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Ron Garan is pleased with his driving practice in the M113 armored personnel carrier, part of emergency training. He and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1182

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Commander Mark Kelly is ready to practice driving the M113 armored personnel carrier as part of emergency training. He and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1180

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Mike Fossum stands ready to practice driving the M113 armored personnel carrier as part of emergency training. He and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1178

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Greg Chamitoff stands ready to practice driving the M113 armored personnel carrier as part of emergency training. He and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1166

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Karen Nyberg waits to begin training on the M113 armored personnel carrier on Launch Pad 39B. She and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1455

NASA Image and Video Library

2008-05-28

CAPE CANAVERAL, Fla. -- After their arrival on the Shuttle Landing Facility at NASA's Kennedy Space Center, the crew members of space shuttle Discovery's STS-124 mission pose for a group photo. From left are Mission Specialists Gregory Chamitoff and Akihiko Hoshide, Pilot Ken Ham, Mission Specialists Karen Nyberg and Mike Fossum, Commander Mark Kelly and Mission Specialist Ron Garan. Launch of Discovery is scheduled for 5:02 p.m. May 31. On the STS-124 mission, the crew of seven will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Photo credit: NASA/Kim Shiflett

Immunization with mutant HPV16 E7 protein inhibits the growth of TC-1 cells in tumor-bearing mice.

PubMed

Li, Yan-Li; Ma, Zhong-Liang; Zhao, Yue; Zhang, Jing

2015-04-01

Two human papillomavirus (HPV) 16 oncogenic proteins, E6 and E7, are co-expressed in the majority of HPV16-induced cervical cancer cells. Thus, the E6 and E7 proteins are good targets for developing therapeutic vaccines for cervical cancer. In the present study, immunization with the mutant non-transforming HPV16 E7 (mE7) protein was demonstrated to inhibit the growth of TC-1 cells in the TC-1 mouse model. The HPV16 mE7 gene was amplified by splicing overlap extension polymerase chain reaction using pET-28a(+)-E7 as a template, and the gene was cloned into pET-28a(+) to form pET-28a(+)-mE7. Compared with the E7 protein, mE7 lacks amino acid residues 94-98, and at residue 24, there is a Cys to Gly substitution. pET-28a(+)-mE7 was then introduced into Escherichia coli Rosetta. The expression of mE7 was induced by isopropyl β-D-1-thiogalactopyranoside. The mE7 protein was purified using Ni-NTA agarose and detected by SDS-PAGE and western blot analysis. In the tumor prevention model, no tumor was detected in the mice vaccinated with the mE7 protein. After 40 days, the tumor-free mice and control mice were challenged with 2×10 5 TC-1 cells. All control mice developed tumors six days later, but mE7 immunized mice were tumor free until 90 days. In the tumor therapy model, the TC-1 cells were initially injected subcutaneously, and the mice were subsequently vaccinated. Vaccination against the mE7 protein may significantly inhibit TC-1 cell growth compared to the control. These results demonstrated that immunization with the HPV16 mE7 protein elicited a long-term protective immunity against TC-1 tumor growth and generated a significant inhibition of TC-1 growth in a TC-1 mouse model.

An iPhone-based digital image colorimeter for detecting tetracycline in milk.

PubMed

Masawat, Prinya; Harfield, Antony; Namwong, Anan

2015-10-01

An iPhone-based digital image colorimeter (DIC) was fabricated as a portable tool for monitoring tetracycline (TC) in bovine milk. An application named ColorConc was developed for the iPhone that utilizes an image matching algorithm to determine the TC concentration in a solution. The color values; red (R), green (G), blue (B), hue (H), saturation (S), brightness (V), and gray (Gr) were measured from each pictures of the TC standard solutions. TC solution extracted from milk samples using solid phase extraction (SPE) was captured and the concentration was predicted by comparing color values with those collected in a database. The amount of TC could be determined in the concentration range of 0.5-10 μg mL(-1). The proposed DIC-iPhone is able to provide a limit of detection (LOD) of 0.5 μg mL(-1) and limit of quantitation (LOQ) of 1.5 μg mL(-1). The enrichment factor was 70 and color of the extracted milk sample was a strong yellow solution after SPE. Therefore, the SPE-DIC-iPhone could be used for the assay of TC residues in milk at the concentration lower than LOD and LOQ of the proposed technique. Copyright © 2015 Elsevier Ltd. All rights reserved.

A preliminary feasibility study of simultaneous dual-isotope imaging with a solid-state dedicated cardiac camera for evaluating myocardial perfusion and fatty acid metabolism.

PubMed

Ko, Toshiyuki; Utanohara, Yuko; Suzuki, Yasuhiro; Kurihara, Makiko; Iguchi, Nobuo; Umemura, Jun; Sumiyoshi, Tetsuya; Tomoike, Hitonobu

2016-01-01

Simultaneous dual-isotope SPECT imaging with 201Tl and (123)I-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) is used to study the perfusion-metabolism mismatch. It predicts post-ischemic functional recovery by detecting stunned myocardium. On the other hand, (99m)Tc-MIBI is another radioisotope widely used in myocardial perfusion imaging because of its better image quality and lower radiation exposure than 201Tl. However, since the photopeak energies of (99m)Tc and (123)I are very similar, crosstalk hampers the simultaneous use of these two radioisotopes. To overcome this problem, we conducted simultaneous dual-isotope imaging study using the D-SPECT scanner (Spectrum-Dynamics, Israel) which has a novel detector design and excellent energy resolution. We first conducted a basic experiment using cardiac phantom to simulate the condition of normal perfusion and impaired fatty acid metabolism. Subsequently, we prospectively recruited 30 consecutive patients who underwent successful percutaneous coronary intervention for acute myocardial infarction, and performed (99m)Tc-MIBI/(123)I-BMIPP dual-isotope imaging within 5 days after reperfusion. Images were interpreted by two experienced cardiovascular radiologists to identify the infarcted and stunned areas based on the coronary artery territories. As a result, cardiac phantom experiment revealed no significant crosstalk between (99m)Tc and (123)I. In the subsequent clinical study, (99m)Tc-MIBI/(123)I-BMIPP dual-isotope imaging in all participant yielded excellent image quality and detected infarcted and stunned areas correctly when compared with coronary angiographic findings. Furthermore, we were able to reduce radiation exposure to significantly approximately one-eighth. In conclusion, we successfully demonstrated the practical application of simultaneous assessment of myocardial perfusion and fatty acid metabolism by (99m)Tc-MIBI and (123)I-BMIPP using a D-SPECT cardiac scanner. Compared with conventional (201)TlCl/(123)I-BMIPP dual-isotope imaging, the use of (99m)Tc-MIBI instead of (201)TlCl improves image quality as well as lowers radiation exposure.

Etude microdosimetrique de l'influence des materiaux sur l'efficacite biologique d'une source d'iode-125

NASA Astrophysics Data System (ADS)

Taschereau, Richard

Cette these concerne les implants permanents pour la prostate. Les isotopes employes, le 103Pd et l'125I, semblent produire les memes resultats cliniques: le premier a cause d'une radiation plus efficace et le second a cause de sa demi-vie plus longue. La recherche utilise le cadre theorique de la microdosimetrie et des simulations Monte Carlo. Elle propose d'employer le spectre d'ejection dans le calcul de l'efficacite; ce changement fait passer l'efficacite relative du 103Pd de 10% a 5%. Elle montre ensuite qu'il est possible d'ameliorer l'efficacite de la radiation de 125I par l'exploitation des rayons X caracteristiques de la capsule. Une source amelioree faite de molybdene et d'yttrium est donnee en exemple. Elle procure une radiation de 5--7% plus efficace, ce qui surclasse les deux sources existantes. Les applications ne se limitent pas au traitement de la prostate; le traitement du melanome oculaire et la curietherapie endovasculaire pourraient en beneficier.

NATO Reference Mobility Model. Edition I. Users Guide. Volume I

DTIC Science & Technology

1979-10-01

C TOTAL ERAKING FCRCE - SCIL /SLOPE/VEHICLE C --- ----.----------- C 275 R-2WJ58# VCLUIJE I PAGE A-103 APPEND-IX A - LISTING CF O.CFAt’ NRtPM C 1...sGCW vN1RAV ,SFTYPC 9TBF I- c r-------------------------~e e C tPAXIMUP BRAKING FCRCE * SCIL /SL OP E/V ENICLE/ DRIVER C --------------------- C C 1. VAR...CONTINUE GO TC 2160 ,ýObO IFl IST ,NE, 21 GC TG 2110i 317 R-20358, VOLUME I PAGE A-145 APPENDIX A - LISTING CF FRGG/iAM NAMM C 8. COARSE GRAINED SCIL IF

Investigation of magnetic order in SmTr2Zn20 (Tr=Fe ,Co,Ru) and SmTr2Cd20 (Tr=Ni ,Pd)

NASA Astrophysics Data System (ADS)

Yazici, D.; White, B. D.; Ho, P.-C.; Kanchanavatee, N.; Huang, K.; Friedman, A. J.; Wong, A. S.; Burnett, V. W.; Dilley, N. R.; Maple, M. B.

2014-10-01

Single crystals of the "cage compounds" SmTr2Zn20 (Tr=Fe, Co, Ru) and SmTr2Cd20 (Tr=Ni, Pd) have been investigated by means of electrical resistivity, magnetization, and specific-heat measurements. The compounds SmFe2Zn20,SmRu2Zn20, and SmNi2Cd20 exhibit ferromagnetic order with Curie temperatures of TC=47.4, 7.6, and 7.5 K, respectively, whereas SmPd2Cd20 is an antiferromagnet with a Néel temperature of TN=3.4 K. No evidence for magnetic order is observed in SmCo2Zn20 down to 110 mK. The Sommerfeld coefficients γ are found to be 57 mJ /molK2 for SmFe2Zn20,79.5 mJ /molK2 for SmCo2Zn20,258 mJ /molK2 for SmRu2Zn20,165 mJ /molK2 for SmNi2Cd20, and 208 mJ /molK2 for SmPd2Cd20. Enhanced values of γ and a quadratic temperature dependence of the electrical resistivity at low temperature for SmRu2Zn20 and SmPd2Cd20 suggest an enhancement of the quasiparticle masses due to hybridization between localized 4f and conduction electron states.

Superconductivity in Cage Compounds LaTr2Al20 with Tr = Ti, V, Nb, and Ta

NASA Astrophysics Data System (ADS)

Yamada, Akira; Higashinaka, Ryuji; Matsuda, Tatsuma D.; Aoki, Yuji

2018-03-01

Electrical resistivity, magnetic susceptibility, and specific heat measurements on single crystals of LaTr2Al20 (Tr = Ti, V, Nb, and Ta) revealed that these four compounds exhibit weak-coupling superconductivity with transition temperatures Tc = 0.46, 0.15, 1.05, and 1.03 K, respectively. LaTi2Al20 is most probably a type-I superconductor, which is quite rare among intermetallic compounds. Single-crystal X-ray diffraction suggests "rattling" anharmonic large-amplitude oscillations of Al ions (16c site) on the Al16 cage, while no such feature is suggested for the cage-center La ion. Using a parameter dGFS quantifying the "guest free space" of the cage-center ion, we demonstrate that nonmagnetic RTr2Al20 superconductors are classified into two groups, i.e., (A) dGFS ≠ 0 and Tc correlates with dGFS, and (B) dGFS ≃ 0 and Tc seems to be governed by other factors.

Classifying Non-Small Cell Lung Cancer by Status of Programmed Cell Death Ligand 1 and Tumor-Infiltrating Lymphocytes on Tumor Cells.

PubMed

Cui, Shaohua; Dong, Lili; Qian, Jialin; Ye, Lin; Jiang, Liyan

2018-01-01

Purpose: To explore the possible correlation between programmed death ligand 1 (PD-L1)/tumor-infiltrating lymphocytes (TIL) status and clinical factors in non-small cell lung (NSCLC). Materials and Methods: A total of 126 surgical NSCLC samples with stage I to IIIA were retrospectively collected and analyzed. Immunohistochemistry (IHC) assays were used to detect PD-L1 protein expression. PD-L1 positivity on tumor cells was defined by positive tumor cell (TC) percentage using 5% cutoff value. Results: Thirty-seven patients (29.4%), thirty patients (23.8%), six patients (4.8%) and fifty-three patients (42%) were classified as type I (PD-L1+, TIL+), type II (PD-L1-, TIL-), type III (PD-L1+, TIL-) and type IV (PD-L1-, TIL+) tumor environments according to PD-L1/TIL status, respectively. Statistical differences could be observed in factors including gender ( P <0.001), smoking status ( P <0.001), age ( P =0.002), histological types ( P <0.001), EGFR mutation ( P =0.008) and KRAS mutation ( P =0.003) across the four type tumors. Type I tumors were associated with ever smoking, non-adenocarcinoma histological types and KRAS mutation. Type II tumors were associated with female gender, never-smoking, adenocarcinoma histological types and EGFR mutation. Type III tumors were associated with ever smoking and type IV tumors were associated with female gender and EGFR mutation. Conclusion: Clinical factors associated with NSCLC microenvironment types based on PD-L1/TIL differed a lot across different types. The findings of this study may help to facilitate the understanding of the relationship between tumor microenvironment and clinical factors, and also the selecting of patients for combination immunotherapies.

Ammunition Cost Research Study. Volume I.

DTIC Science & Technology

1983-01-01

0.048 4,000,000 1.72 1.74 M717 PD 0.25 571,490 8.22 6.13 M567 PD 1.30 300,000 10.43 17.22 M503A2 PD 0.34 814,701 10.64 7.28 M739 PD 1.43 915,837 10.65...M503A2 PD 0.34 252,336 10.73 7.58 M567 PD 1.30 1,071,100 11.23 16.29 M739 PD 1.43 915,837 11.30 17.47 M720 PD 2.10 90,000 11.41 23.46 m567 PD 1.30...14.86 12.91 M524A6 PD 1.27 3,982,150 15.11 13.04 M524A6 PD 1.27 3,181,102 15.44 13.81 M739 PD 1.43 3,168,072 15.47 14.86 M524A6 PD 1.27 3,045,000 17.37

The diversity of the Chagas parasite, Trypanosoma cruzi, infecting the main Central American vector, Triatoma dimidiata, from Mexico to Colombia

PubMed Central

Waleckx, Etienne; Woods, Adrienne S.; Monroy, Maria Carlota; Stevens, Lori

2017-01-01

Little is known about the strains of Trypanosoma cruzi circulating in Central America and specifically in the most important vector in this region, Triatoma dimidiata. Approximately six million people are infected with T. cruzi, the causative agent of Chagas disease, which has the greatest negative economic impact and is responsible for ~12,000 deaths annually in Latin America. By international consensus, strains of T. cruzi are divided into six monophyletic clades called discrete typing units (DTUs TcI-VI) and a seventh DTU first identified in bats called TcBat. TcI shows the greatest geographic range and diversity. Identifying strains present and diversity within these strains is important as different strains and their genotypes may cause different pathologies and may circulate in different localities and transmission cycles, thus impacting control efforts, treatment and vaccine development. To determine parasite strains present in T. dimidiata across its geographic range from Mexico to Colombia, we isolated abdominal DNA from T. dimidiata and determined which specimens were infected with T. cruzi by PCR. Strains from infected insects were determined by comparing the sequence of the 18S rDNA and the spliced-leader intergenic region to typed strains in GenBank. Two DTUs were found: 94% of infected T. dimidiata contained TcI and 6% contained TcIV. TcI exhibited high genetic diversity. Geographic structure of TcI haplotypes was evident by Principal Component and Median-Joining Network analyses as well as a significant result in the Mantel test, indicating isolation by distance. There was little evidence of association with TcI haplotypes and host/vector or ecotope. This study provides new information about the strains circulating in the most important Chagas vector in Central America and reveals considerable variability within TcI as well as geographic structuring at this large geographic scale. The lack of association with particular vectors/hosts or ecotopes suggests the parasites are moving among vectors/hosts and ecotopes therefore a comprehensive approach, such as the Ecohealth approach that makes houses refractory to the vectors will be needed to successfully halt transmission of Chagas disease. PMID:28957315

SU-F-T-44: A Comparison of the Pre-Plan, Intra-Operative Plan, and Post-Implant Dosimetry for a Prostate Implant Case Using Prefabricated Linear Polymer-Encapsulated Pd-103

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

Sheu, R; Powers, A; McGee, H

Purpose: To investigate the reproducibility and limitations of Pd-103 prostate brachytherapy using fixed length linear sources (CivaString). Methods: An LDR prostate brachytherapy case which was preplanned on MR images with prefabricated linear polymer-encapsulated Pd-103 sources (CivaString) was studied and compared with ultrasound based intra-operative planning and CT based post-implant dosimetry. We evaluated the following parameters among the three studies: prostate geometry (volume and cross sectional area), needle position and alignment deviations, and dosimetry parameters (D90). Results: The prostate volumes and axial cross sectional areas at center of prostate were measured as 41.8, 39.3 and 36.8 cc, and 14.9, 14.3, andmore » 11.3 respectively on pre-plan MR, inter-op US, and post-implant CT studies. The deviation of prostate volumes and axial cross sectional areas measured on pre-planning MR and intra-operative US were within 5%. 17 out of 19 pre-planned needles were positioned within 5mm (the template grid size). One needle location was adjusted intra-operatively and another needle was removed due to proximity to urethra. The needle pathways were not always parallel to the trans-rectal probe due to the flexibility of CivaString. The angle of deviation was up to 10 degrees. Two pairs of needles were exchanged to better fit the length of prostate at the time of implant. This resulted in a prostate D90 of 153.8 Gy (124%) and 131.4 Gy (106.7%) for intra-op and PID respectively. Conclusion: Preplanning is a necessary part of implants performed with prefabricated linear polymer sources. However, as is often the case, there were real-time deviations from the pre-plan. Intra-op planning provides the ability conform to anatomy at the time of implant. Therefore, we propose to develop a systematic way to order extra strings of different length to provide the flexibility to perform intra-operative planning with fixed length strands.« less

Effects of N-acetylcysteine and terbutaline treatment on hemodynamics and regional albumin extravasation in porcine septic shock

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

Groeneveld, A.B.; den Hollander, W.; Straub, J.

We studied the therapeutic effects of continuously infused N-acetylcysteine, an O2 radical scavenger (N, n = 6), and terbutaline, a beta 2-agonist (T, n = 6), versus dextrose (controls C, N = 6) on hemodynamics and regional albumin extravasation in porcine septic shock. After instrumentation, injection of 99mTc-labeled red blood cells, and baseline measurements, pigs received a 90 min infusion of 11 +/- 9 X 10(8).kg-1 live Escherichia coli bacteria. Thereafter, therapy was started, and 131I human serum albumin was injected. Images were obtained hourly using a gamma camera and a computer until 5 hours after baseline. Regions of interestmore » were drawn in the 99mTc images, yielding regional 131I/99mTc radioactivity ratios, with blood samples as reference. From these ratios, an albumin leak index, a rate constant of transvascular albumin transport, was calculated. Control pigs developed pulmonary hypertension, arterial hypotension, hemoconcentration, and lactic acidemia. In spite of tachycardia and unchanged filling pressures, cardiac output fell. In arterial blood, white cell count, PO2, albumin level, and colloid osmotic pressure fell. The albumin leak index (X10(-3).min-1) measured 1.56 +/- 0.59 over the lungs and 2.87 +/- 1.19 over the abdomen in C, confirming previously found increased albumin flux in both lung and abdomen, the latter exceeding the former. Neither N nor T significantly affected hemodynamic and biochemical changes. The drugs neither decreased the regional albumin leak index nor attenuated the formation of albumin-rich ascites found at autopsy. However, the lung albumin index obtained at autopsy was significantly reduced with N (P less than .01 vs. C), at similar gravimetrically determined extravascular lung water (EVLW). EVLW positively correlated with pulmonary albumin extravasation in C and T but not in N.« less

Condensed Matter Nuclear Science

NASA Astrophysics Data System (ADS)

Takahashi, Akito; Ota, Ken-Ichiro; Iwamura, Yashuhiro

Preface -- 1. General. Progress in condensed matter nuclear science / A. Takahashi. Summary of ICCF-12 / X. Z. Li. Overview of light water/hydrogen-based low-energy nuclear reactions / G. H. Miley and P. J. Shrestha -- 2. Excess heat and He detection. Development of "DS-reactor" as the practical reactor of "cold fusion" based on the "DS-cell" with "DS-cathode" / Y. Arata and Y.-C. Zhang. Progress in excess of power experiments with electrochemical loading of deuterium in palladium / V. Violante ... [et al.]. Anomalous energy generation during conventional electrolysis / T. Mizuno and Y. Toriyabe. "Excess heat" induced by deuterium flux in palladium film / B. Liu ... [et al.]. Abnormal excess heat observed during Mizuno-type experiments / J.-F. Fauvarque, P. P. Clauzon and G. J.-M. Lallevé. Seebeck envelope calorimetry with a Pd|D[symbol]O + H[symbol]SO[symbol] electrolytic cell / W.-S. Zhang, J. Dash and Q. Wang. Observation and investigation of nuclear fusion and self-induced electric discharges in liquids / A. I. Koldamasov ... [et al.]. Description of a sensitive seebeck calorimeter used for cold fusion studies / E. Storms. Some recent results at ENEA / M. Apicella ... [et al.]. Heat measurement during plasma electrolysis / K. Iizumi ... [et al.]. Effect of an additive on thermal output during electrolysis of heavy water with a palladium cathode / Q. Wang and J. Dash. Thermal analysis of calorimetric systems / L. D'Aulerio ... [et al.]. Surface plasmons and low-energy nuclear reactions triggering / E. Castagna ... [et al.]. Production method for violent TCB jet plasma from cavity / F. Amini. New results and an ongoing excess heat controversy / L. Kowalski ... [et al.] -- 3. Transmutation. Observation of surface distribution of products by X-ray fluorescence spectrometry during D[symbol] gas permeation through Pd Complexes / Y. Iwamura ... [et al.]. Discharge experiment using Pd/CaO/Pd multi-layered cathode / S. Narita ... [et al.]. Producing transmutation element on multi-layered Pd sample by deuterium permeation / H. Yamada ... [et al.]. Experimental observation and combined investigation of high-performance fusion of iron-region isotopes in optimal growing microbiological associations / V. I. Vysotskii ... [et al.]. Research into low-energy nuclear reactions in cathode sample solid with production of excess heat, stable and radioactive impurity nuclides / A. B. Karabut. Influence of parameters of the glow discharge on change of structure and the isotope composition of the cathode materials / I. B. Savvatimova and D. V. Gavritenkov. Elemental analysis of palladium electrodes after Pd/Pd light water critical electrolysis / Y. Toriyabe ... [et al.]. Progress on the study of isotopic composition in metallic thin films undergone to electrochemical loading of hydrogen / M. Apicella ... [et al.]. In situ accelerator analyses of palladium complex under deuterium permeation / A. Kitamura ... [et al.]. High-resolution mass spectrum for deuterium (hydrogen) gas permeating palladium film / Q. M. Wei ... [et al.]. ICP-MS analysis of electrodes and electrolytes after HNO[symbol]/H[symbol]O electrolysis / S. Taniguchi ... [et al.]. The Italy-Japan project - fundamental research on cold transmutation process for treatment of nuclear wastes / A. Takahashi, F. Celani and Y. Iwamura -- 4. Nuclear physics approach. Reproducible nuclear emissions from Pd/PdO:Dx heterostructure during controlled exothermic deuterium desorption / A. G. Lipson ... [et al.]. Correct identification of energetic alpha and proton tracks in experiments on CR-39 charged particle detection during hydrogen desorption from Pd/PdO:H[symbol] heterostructure / A. S. Roussetski ... [et al.]. Intense non-linear soft X-ray emission from a hydride target during pulsed D bombardment / G. H. Miley ... [et al.]. Enhancement of first wall damage in ITER type TOKAMAK due to LENR effects / A. G. Lipson, G. H. Miley and H. Momota. Generation of DD-reactions in a ferroelectric KD[symbol]PO[symbol] single crystal during transition through curie point (Tc = 220K) / A. G. Lipson ... [et al.]. Study of energetic and temporal characteristics of X-ray emission from solid-state cathode medium of high-current glow discharge / A. B. Karabut. A novel LiF-based detector for X-ray imaging in hydrogen loaded Ni films under laser irradiation / R. M. Montereali ... [et al.]. Observation and modeling of the ordered motion of hypothetical magnetically charged particles on the multilayer surface and the problem of low-energy fusion / S. V. Adamenko and V. I. Vysotskii -- 5. Material science. Evidence of superstoichiometric H/D lenr active sites and high-temperature superconductivity in a hydrogen-cycled Pd/PdO / A. G. Lipson ... [et al.]. New procedures to make active, fractal-like surfaces on thin Pd wires / F. Celani ... [et al.]. Using resistivity to measure H/Pd and D/Pd loading: Method and significance / M. C. H. McKubre and F. L. Tanzella. Measurements of the temperature coefficient of electric resistivity of hydrogen overloaded Pd / A. Spallone ... [et al.]. Magnetic interaction of hypothetical particles moving beneath the electrode/electrolyte interface to elucidate evolution mechanism of vortex appeared on Pd surface after long-term evolution of deuterium in 0.1 m LiOD / H. Numata and M. Ban. Unusual structures on the material surfaces irradiated by low-energy ions / B. Rodionov and I. Savvatimova -- 6. Theory. Context for understanding why particular nanoscale crystals turn-on faster and other LENR effects / S. R. Chubb. Models for anomalies in condensed matter deuterides / P. L. Hagelstein. Time-dependent EQPET analysis of TSC / A. Takahashi. Unifying theory of low-energy nuclear reaction and transmutation processes in deuterated/hydrogenated metals, acoustic cavitation, glow discharge, and deuteron beam experiments / Y. E. Kim and A. L. Zubarev. Catalytic fusion and the interface between insulators and transition metals / T. A. Chubb. Multiple scattering of deuterium wave function near surface of palladium lattice / X. Z. Li ... [et al.]. Theoretical comparison between semi-classical and quantum tunneling effect / F. Frisone. New cooperative mechanisms of low-energy nuclear reactions using super low-energy external field / F. A. Gareev and I. E. Zhidkova. Polyneutron theory of transmutation / J. C. Fisher. The thermal conduction from the centers of the nuclear reactions in solids / K.-I. Tsuchiya. Four-body RST general nuclear wavefunctions and matrix elements / I. Chaudhary and P. L. Hagelstein. Study on formation of tetrahedral or octahedral symmetric condensation by hopping of alkali or alkaline-earth metal ion / H. Miura. Calculations of nuclear reactions probability in a crystal lattice of lanthanum deuteride / V. A. Kirkinskii and Yu. A. Novikov. Possible coupled electron and electron neutrino in nucleus and its physical catalysis effect on D-D cold fusion into helium in Pd / M. Fukuhara. Tunnel resonance of electron wave and force of fluctuation / M. Ban. Types of nuclear fusion in solids / N. Yabuuchi. Neutrino-dineutron reactions (low-energy nuclear reactions induced by D[symbol] gas permeation through Pd complexes - Y. Iwamura effect) / V. Muromtsev, V. Platonov and I. Savvatimova. An explanation of earthquakes by the blacklight process and hydrogen fusion / H. Yamamoto. Theoretical modeling of electron flow action on probability of nuclear fusion of deuterons / A. I. Goncharov and V. A. Kirkinskii.

Genetic and biochemical findings in Chinese children with Leigh syndrome.

PubMed

Ma, Yan-Yan; Wu, Tong-Fei; Liu, Yu-Peng; Wang, Qiao; Song, Jin-Qing; Li, Xi-Yuan; Shi, Xiu-Yu; Zhang, Wei-Na; Zhao, Meng; Hu, Lin-Yan; Yang, Yan-Ling; Zou, Li-Ping

2013-11-01

This study investigated the genetic and enzymological features of Leigh syndrome due to respiratory chain complex deficiency in Chinese patients. The clinical features of 75 patients were recorded. Mitochondrial respiratory chain enzyme activities were determined via spectrophotometry. Mitochondrial gene sequence analysis was performed in 23 patients. Five core pedigrees were investigated via restriction fragment length polymorphism and gene sequencing. Psychomotor retardation (55%), motor regression (20%), weakness (29%), and epilepsy (25%) were the most frequent manifestations. Sixty-four patients (85.3%) had isolated respiratory complex deficiencies: complex I was seen in 28 patients (37.3%); complex II, seven (9.3%); complex III, six (8%); complex IV, ten (13.3%); and complex V, 13 patients (17.3%). Eleven patients (14.7%) had combined complex deficiencies. Mitochondrial DNA mutations were detected in 10 patients. Eight point mutations were found in mitochondrial structural genes: m.4833A>G in ND2, m.10191T>C in ND3, m.12338T>C and m.13513G>A in ND5, m.14502T>C and m.14487T>C in ND6, m.8108A>G in COXII, and m.8993T>G in ATPase6. Three mutations were found in tRNA genes: m.4395A>G in tRNA-Gln, m.10454T>C in tRNA-Arg, and m.5587T>C in tRNA-Ala. One patient and their mother both had the m.12338T>C and m.8993T>C mutations. In conclusion, mitochondrial respiratory chain complex I deficiency and structural gene mutations frequently occur in Chinese Leigh syndrome patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Prime Contract Awards Alphabetically by Contractor, by State or Country, and Place, Fiscal Year 1987. Part 8. General Fire Extinguisher Del.-Hawthorne of Missouri, Incorporated.

DTIC Science & Technology

1987-01-01

0-4 .4n~(D r-4.4.4.--00-4N -4O4N4N Q 103 (n 0 l 0 I I toN (n oC 00 0 000000c000 o 0000 00 4i 0000000000000000000000000 00000000 -0 1I00007mo 00...Ij 0 0 00 0000 0 o 7Ŕ CA 00O Io L) ’- I- 4n (oWI W rh - 4 -4 - "oi Io DO Io .- D 01 4NCA 00 01 n0) 0) 0) z0 NI -4 coo N I3 OO I y)W( -4 -0 -4 4 4 0 0...4 00 00 C’) C) 0D 0-4 000 In 0 0 0- 00030 00000 蓐 M40) 1 Co W- Inco COW(D’ CO I CIDr CO r-Cr--- 0 pC-- pD (-pW r--r.-ow0 -4) ow ow 0000 COCOCO

Didanosine, lamivudine, and efavirenz versus zidovudine, lamivudine, and efavirenz for the initial treatment of HIV type 1 infection: final analysis (48 weeks) of a prospective, randomized, noninferiority clinical trial, GESIDA 3903.

PubMed

Berenguer, Juan; González, Juan; Ribera, Esteban; Domingo, Pere; Santos, Jesús; Miralles, Pilar; Angels Ribas, M; Asensi, Víctor; Gimeno, Juan Luis; Pérez-Molina, José Antonio; Terrón, José Alberto; Santamaría, Juan Miguel; Pedrol, Enric

2008-10-15

The combination of didanosine, lamivudine, and efavirenz (ddI/3TC/EFV) for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection has been insufficiently analyzed in clinical trials. We conducted an open-label, randomized study to compare the noninferiority of ddI/3TC/EFV with the lamivudine-zidovudine tablet and EFV (COM/EFV), both administered with food to improve tolerability and convenience. Patients were stratified by HIV-1 RNA level of <5.0 log(10) or > or =5.0 log(10) copies/mL. The primary end point was the percentage of patients with an HIV-1 RNA level of <50 copies/mL at week 48, determined by intention-to-treat analysis. Three hundred sixty-nine patients were randomized: 186 for ddI/3TC/EFV treatment and 183 for COM/EFV treatment. Both groups were well matched in terms of baseline characteristics; 19.3% of patients received a Centers for Disease Control and Prevention assessment of clinical category C, median HIV RNA level was 5.0 log(10) copies/mL, and median CD4(+) cell count was 208 cells/microL. At week 48, by intention-to-treat analysis, 70% of patients in the ddI/3TC/EFV group and 63% of patients in the COM/EFV group had an HIV-1 RNA level of <50 copies/mL (treatment difference, 7.1%; 95% confidence interval, -2.39% to 16.59%). Fourteen patients (8%) in the ddI/3TC/EFV arm (not the COM/EFV arm) and 26 patients (14%) in the COM/EFV arm (not the ddI/3TC/EFV arm) [corrected] discontinued the study medication because of adverse events (P = .046). One patient (1%) in the ddI/3TC/EFV arm and 11 patients (6%) in the COM/EFV arm discontinued medication because of hematological toxicity (P = .003). At week 48, ddI/3TC/EFV administered once per day with food did not have results inferior to those of COM/EFV treatment. A statistically significantly higher proportion of patients in the COM/EFV arm than in the ddI/3TC/EFV arm discontinued therapy because of adverse events, mainly because of hematological toxicity. NCT00256828.

KSC-08pd1728

NASA Image and Video Library

2008-06-14

CAPE CANAVERAL, Fla. – The STS-124 mission crew pose for a final group photo before heading to crew quarters after their successful landing aboard space shuttle Discovery on Runway 15 at NASA's Kennedy Space Center. The landing ended a 14-day mission to the International Space Station. From left are Pilot Ken Ham, Mission Specialists Karen Nyberg and Akihiko Hoshide, Commander Mark Kelly, and Mission Specialists Mike Fossum and Ron Garan. Discovery's main landing gear touched down at 11:15:19 a.m. EDT. The nose landing gear touched down at 11:15:30 a.m. and wheel stop was at 11:16:19 a.m. The mission completed 5.7 million miles. The STS-124 mission delivered the Japan Aerospace Exploration Agency's large Japanese Pressurized Module and its remote manipulator system to the space station. Photo credit: NASA/Kim Shiflett

Ti–Ag–Pd alloy with good mechanical properties and high potential for biological applications

PubMed Central

Zadorozhnyy, V. Yu.; Shi, X.; Gorshenkov, M. V.; Kozak, D. S.; Wada, T.; Louzguine-Luzgin, D. V.; Inoue, A.; Kato, H.

2016-01-01

Ti-based alloys containing Ag were produced by tilt-casting method and their properties were studied. Even in its as-cast state, Ti94Ag3Pd3 showed relatively high tensile properties, good electrochemical behavior, and good biocompatibility. The relatively good mechanical properties of the as-cast α-Ti-type Ti94Ag3Pd3 alloy (tensile strength up to 850 MPa and elongation of ~10%) can be explained by its severely deformed, fine crystalline structure. The high biocompatibility of Ti94Ag3Pd3 can be explained by the Ag–Pd interaction, which inhibits the release of Ag ions from the surface. Ag, in combination with Pd has no toxic effects and demonstrates useful antimicrobial properties. The Ti94Ag3Pd3 alloy shows a good potential to be applied as a biomedical implant alloy. PMID:27122177

FRAMING Linguistics: ``SEANCES"(!!!) Martin-Bradshaw-Siegel ``Buzzwordism, Bandwagonism, Sloganeering For:Fun, Profit, Survival, Ego": Rampant UNethics Sociological-DYSfunctionality!!!

NASA Astrophysics Data System (ADS)

Bradshaw, John; Siegel, E.

2010-03-01

``Sciences''/SEANCES(!!!) rampant UNethics!!! WITNESS: Yau v Perelman Poincare-conj.-pf. [Naser, NewYorker(8/06)]; digits log- law Siegel[AMS Nat.Mtg.(02)-Abs.973-60-124] inversion to ONLY BEQS: Newcomb(1881)<<

A survey of physics and dosimetry practice of permanent prostate brachytherapy in the United States.

PubMed

Prete, J J; Prestidge, B R; Bice, W S; Friedland, J L; Stock, R G; Grimm, P D

1998-03-01

To obtain data with regard to current physics and dosimetry practice in transperineal interstitial permanent prostate brachytherapy (TIPPB) in the U.S. by conducting a survey of institutions performing this procedure with the greatest frequency. Seventy brachytherapists with the greatest volume of TIPPB cases in 1995 in the U.S. were surveyed. The four-page comprehensive questionnaire included questions on both clinical and physics and dosimetry practice. Individuals not responding initially were sent additional mailings and telephoned. Physics and dosimetry practice summary statistics are reported. Clinical practice data is reported separately. Thirty-five (50%) surveys were returned. Participants included 29 (83%) from the private sector and 6 (17%) from academic programs. Among responding clinicians, 125I (89%) is used with greater frequency than 103Pd (83%). Many use both (71%). Most brachytherapists perform preplans (86%), predominately employing ultrasound imaging (85%). Commercial treatment planning systems are used more frequently (75%) than in-house systems (25%). Preplans take 2.5 h (avg.) to perform and are most commonly performed by a physicist (69%). A wide range of apparent activities (mCi) is used for both 125I (0.16-1.00, avg. 0.41) and 103Pd (0.50-1.90, avg. 1.32). Of those assaying sources (71%), the range in number assayed (1 to all) and maximum accepted difference from vendor stated activity (2-20%) varies greatly. Most respondents feel that the manufacturers criteria for source activity are sufficiently stringent (88%); however, some report that vendors do not always meet their criteria (44%). Most postimplant dosimetry imaging occurs on day 1 (41%) and consists of conventional x-rays (83%), CT (63%), or both (46%). Postimplant dosimetry is usually performed by a physicist (72%), taking 2 h (avg.) to complete. Calculational formalisms and parameters vary substantially. At the time of the survey, few institutions have adopted AAPM TG-43 recommendations (21%). Only half (50%) of those not using TG-43 indicated an intent to do so in the future. Calculated doses at 1 cm from a single 1 mCi apparent activity source permanently implanted varied significantly. For 125I, doses calculated ranged from 13.08-40.00 Gy and for 103Pd, from 3.10 to 8.70 Gy. While several areas of current physics and dosimetry practice are consistent among institutions, treatment planning and dose calculation techniques vary considerably. These data demonstrate a relative lack of consensus with regard to these practices. Furthermore, the wide variety of calculational techniques and benchmark data lead to calculated doses which vary by clinically significant amounts. It is apparent that the lack of standardization with regard to treatment planning and dose calculation practice in TIPPB must be addressed prior to performing any meaningful comparison of clinical results between institutions.

High-level coproduction, purification and characterisation of laccase and exopolysaccharides by Coriolus versicolor.

PubMed

Que, Youxiong; Sun, Shujing; Xu, Liping; Zhang, Yuye; Zhu, Hu

2014-09-15

In this study, a two-stage pH-shift fermentation process was developed for the coproduction of laccase and exopolysaccharides (EPS) by Coriolus versicolor. At the same time, laccase and EPS were purified and characterised in detail. The results showed that the highest laccase and EPS production reached 7680 U l(-1) and 8.2 g l(-1). Furthermore, the flow behaviour of fermentation broth was Newtonian and the maximum μ(ap) was 2.7×10(-3) Pa s. The MW of laccase was 64 kDa and it showed a pI value of 4.2. The CD analysis showed that laccase had a high α-helical content (68%). The MW of the purified EPS was determined to be 1.8×10(6) Da, consisting of carbohydrates (87.6%) and proteins (12.4%). The EPS consisted of 17 amino acids, mainly serine (11.3%), glutamic acid (12.60%), leucine (13.3%) and phenylalanine (9.4%) in protein moiety, and three monosaccharides (galactose, mannose and xylose). Copyright © 2014 Elsevier Ltd. All rights reserved.

Tuneable reactivity with PPh3 and SnX2 of four- and five-coordinate Pd(II) and Pt(II) complexes containing polyphosphines.

PubMed

Fernández-Anca, Damián; García-Seijo, M Inés; García-Fernández, M Esther

2013-07-28

The reactivity of the unusual d(8) trigonal-bipyramidal systems [MX(PP3)]X (X = Cl: M = Pd(1a), Pt(2a); X = Br: M = Pd(3a), Pt(4a); X = I: M = Pd(5a), Pt(6a); PP3 = tris[2-(diphenylphosphino)ethyl]phosphine) in CHCl3-CH3OH, the square-pyramidal compounds [MCl(NP3)]Cl (M = Pd(7a); Pt(8a); NP3 = tris[2-(diphenylphosphino)ethyl]amine) in CD3OD-DMF and the distorted square-planar mononuclear [MX(PNP)]X (M = Pd: X = Cl(10a); M = Pt: X = I(10b); PNP = bis[2-(diphenylphosphino)ethyl]amine) and the heteronuclear [PdAu2X4(PP3)] [X = I(9a), Cl(14a), Br(15a)] and [MAuX2(PP3)]X [M = Pd: X = Cl(16a); M = Pt: X = Cl(17a), Br(18a)] species in CDCl3 with PPh3 + SnX2 has been explored to establish the factors that influence the nature of the products. With the mononuclear precursors the course of the reaction is strongly dependent on the tripodal or linear arrangement of the polydentate ligand and in the former case on the halogen. Thus, while for chlorides (1a-2a, 7a-8a) and bromides (3a-4a) the reaction led to the trigonal-bipyramidal compounds [M(SnCl3)(AP3)][SnCl3] [A = P: M = Pd(1), Pt(2); A = N: M = Pd(7), Pt(8)], [MBr(PP3)][SnBr3] [M = Pd(4), Pt(6)] containing M-Sn and M-Br bonds, respectively, for iodides (5a-6a) resulted in the unknown neutral square-planar compounds [MI2(PP(PO)2)(SnI2)2] [M = Pd(9) and Pt(10)] bearing two dangling P=O-SnI2 units and P2MI2 environments. However, complexes of the type [PtCl(PP2PO)X]X' [X = SnCl2, X' = [SnCl3](-)(11)] and [M(PP(PO)2)2X4]X'2 [X = SnCl2, X' = [SnCl3](-): M = Pd(12), Pt(13)] showing P=O-SnCl2 arms were obtained by direct reaction of [PtCl(PP2PO)]Cl (11a) and [M(PP(PO)2)2]Cl2 [M = Pd(12a), Pt(13a)] with SnCl2 in CH3OH. Although complex 9 was also prepared by interaction of the heteronuclear iodide 9a with PPh3 + SnI2 in CDCl3, the use of the neutral and ionic heteronuclear chlorides and bromides (14a-18a) as starting materials afforded the distorted square-planar ionic systems [MAuX'(PP3)(PPh3)][SnX3]2 [M = Pd: X = Cl, X' = SnCl3(-)(14); X = Br, X' = SnBr3(-)(15); M = Pt: X = Cl, X' = SnCl3(-)(17); X = Br, X' = SnBr3(-)(18)] containing M-SnX3 and P-Au-PPh3 functionalities. It was found that these reactions where the heteronuclear species are the precursors proceed via the trigonal-bipyramidal halides not only with X = Cl and Br(1a-4a) but also I(5a). When the precursors were 10a and 10b the reaction occurred with formation of [Pd(PNP)(PPh3)][SnCl3]2 (23) and [Pt(PNP)(PPh3)][SnCl2I]2 (24) showing M-PPh3 units and trihalostannato counter anions.

Cu-free 1,3-dipolar cycloaddition click reactions to form isoxazole linkers in chelating ligands for fac-[M(I)(CO)3]+ centers (M = Re, 99mTc).

PubMed

Bottorff, Shalina C; Kasten, Benjamin B; Stojakovic, Jelena; Moore, Adam L; MacGillivray, Leonard R; Benny, Paul D

2014-02-17

Isoxazole ring formation was examined as a potential Cu-free alternative click reaction to Cu(I)-catalyzed alkyne/azide cycloaddition. The isoxazole reaction was explored at macroscopic and radiotracer concentrations with the fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) core for use as a noncoordinating linker strategy between covalently linked molecules. Two click assembly methods (click, then chelate and chelate, then click) were examined to determine the feasibility of isoxazole ring formation with either alkyne-functionalized tridentate chelates or their respective fac-[M(I)(CO)3](+) complexes with a model nitrile oxide generator. Macroscale experiments, alkyne-functionalized chelates, or Re complexes indicate facile formation of the isoxazole ring. (99m)Tc experiments demonstrate efficient radiolabeling with click, then chelate; however, the chelate, then click approach led to faster product formation, but lower yields compared to the Re analogues.

Trypanosoma cruzi I genotypes in different geographic regions and transmission cycles based on a microsatellite motif of the intergenic spacer of spliced leader genes✯

PubMed Central

Cura, Carolina I.; Mejía-Jaramillo, Ana M.; Duffy, Tomás; Burgos, Juan M.; Rodriguero, Marcela; Cardinal, Marta V.; Kjos, Sonia; Gurgel-Gonçalves, Rodrigo; Blanchet, Denis; De Pablos, Luis M.; Tomasini, Nicolás; Silva, Alex Da; Russomando, Graciela; Cuba Cuba, Cesar A.; Aznar, Christine; Abate, Teresa; Levin, Mariano J.; Osuna, Antonio; Gürtler, Ricardo E.; Diosque, Patricio; Solari, Aldo; Triana-Chávez, Omar; Schijman, Alejandro G.

2011-01-01

The intergenic region of spliced-leader (SL-IR) genes from 105 Trypanosoma cruzi I (Tc I) infected biological samples, culture isolates and stocks from 11 endemic countries, from Argentina to the USA were characterised, allowing identification of 76 genotypes with 54 polymorphic sites from 123 aligned sequences. On the basis of the microsatellite motif proposed by Herrera et al. (2007) to define four haplotypes in Colombia, we could classify these genotypes into four distinct Tc I SL-IR groups, three corresponding to the former haplotypes Ia (11 genotypes), Ib (11 genotypes) and Id (35 genotypes); and one novel group, Ie (19 genotypes). Genotypes harboring the Tc Ic motif were not detected in our study. Tc Ia was associated with domestic cycles in southern and northern South America and sylvatic cycles in Central and North America. Tc Ib was found in all transmission cycles from Colombia. Tc Id was identified in all transmission cycles from Argentina and Colombia, including Chagas cardiomyopathy patients, sylvatic Brazilian samples and human cases from French Guiana, Panama and Venezuela. Tc Ie gathered five samples from domestic Triatoma infestans from northern Argentina, nine samples from wild Mepraia spinolai and Mepraia gajardoi and two chagasic patients from Chile and one from a Bolivian patient with chagasic reactivation. Mixed infections by Tc Ia + Tc Id, Tc Ia + Tc Ie and Tc Id + Tc Ie were detected in vector faeces and isolates from human and vector samples. In addition, Tc Ia and Tc Id were identified in different tissues from a heart transplanted Chagas cardiomyopathy patient with reactivation, denoting histotropism. Trypanosoma cruzi I SL-IR genotypes from parasites infecting Triatoma gerstaeckeri and Didelphis virginiana from USA, T. infestans from Paraguay, Rhodnius nasutus and Rhodnius neglectus from Brazil and M. spinolai and M. gajardoi from Chile are to our knowledge described for the first time. PMID:20670628

Coordination modes of multidentate ligands in fac-[Re(CO)(3)(polyaminocarboxylate)] analogues of (99m)Tc radiopharmaceuticals. dependence on aqueous solution reaction conditions.

PubMed

Lipowska, Malgorzata; He, Haiyang; Xu, Xiaolong; Taylor, Andrew T; Marzilli, Patricia A; Marzilli, Luigi G

2010-04-05

We study Re analogues of (99m)Tc renal agents to interpret previous results at the (99m)Tc tracer level. The relative propensities of amine donors versus carboxylate oxygen donors of four L = polyaminocarboxylate ligands to coordinate in fac-[Re(I)(CO)(3)L](n) complexes were assessed by examining the reaction of fac-[Re(I)(CO)(3)(H(2)O)(3)](+) under conditions differing in acidity and temperature. All four L [N,N-bis-(2-aminoethyl)glycine (DTGH), N,N-ethylenediaminediacetic acid, diethylenetriamine-N-malonic acid, and diethylenetriamine-N-acetic acid] can coordinate as tridentate ligands while creating a dangling chain terminated in a carboxyl group. Dangling carboxyl groups facilitate renal clearance in fac-[(99m)Tc(I)(CO)(3)L](n) agents. Under neutral conditions, the four ligands each gave two fac-[Re(I)(CO)(3)L](n) products with HPLC traces correlating well with known traces of the fac-[(99m)Tc(I)(CO)(3)L](n) mixtures. Such mixtures are common in renal agents because the needed dangling carboxyl group can compete for a coordination site. However, the HPLC separations needed to assess the biodistribution of a single tracer are impractical in a clinical setting. One goal in investigating this Re chemistry is to identify conditions for avoiding this problem of mixtures in preparations of fac-[(99m)Tc(I)(CO)(3)L](n) renal tracers. After separation and isolation of the fac-[Re(I)(CO)(3)L](n) products, NMR analysis of all products and single crystal X-ray crystallographic analysis of both DTGH products, as well as one product each from the other L, allowed us to establish coordination mode unambiguously. The product favored in acidic conditions has a dangling amine chain and more bound oxygen. The product favored in basic conditions has a dangling carboxyl chain and more bound nitrogen. At the elevated temperatures used for simulating tracer preparation, equilibration was facile (ca. 1 h or less), allowing selective formation of one product by utilizing acidic or basic conditions. The results of this fundamental study offer protocols and guidance useful for the design and preparation of fac-[(99m)Tc(I)(CO)(3)L](n) agents consisting of a single tracer.

Evaluation of a CdTe semiconductor based compact γ camera for sentinel lymph node imaging.

PubMed

Russo, Paolo; Curion, Assunta S; Mettivier, Giovanni; Esposito, Michela; Aurilio, Michela; Caracò, Corradina; Aloj, Luigi; Lastoria, Secondo

2011-03-01

The authors assembled a prototype compact gamma-ray imaging probe (MediPROBE) for sentinel lymph node (SLN) localization. This probe is based on a semiconductor pixel detector. Its basic performance was assessed in the laboratory and clinically in comparison with a conventional gamma camera. The room-temperature CdTe pixel detector (1 mm thick) has 256 x 256 square pixels arranged with a 55 microm pitch (sensitive area 14.08 x 14.08 mm2), coupled pixel-by-pixel via bump-bonding to the Medipix2 photon-counting readout CMOS integrated circuit. The imaging probe is equipped with a set of three interchangeable knife-edge pinhole collimators (0.94, 1.2, or 2.1 mm effective diameter at 140 keV) and its focal distance can be regulated in order to set a given field of view (FOV). A typical FOV of 70 mm at 50 mm skin-to-collimator distance corresponds to a minification factor 1:5. The detector is operated at a single low-energy threshold of about 20 keV. For 99 mTc, at 50 mm distance, a background-subtracted sensitivity of 6.5 x 10(-3) cps/kBq and a system spatial resolution of 5.5 mm FWHM were obtained for the 0.94 mm pinhole; corresponding values for the 2.1 mm pinhole were 3.3 x 10(-2) cps/kBq and 12.6 mm. The dark count rate was 0.71 cps. Clinical images in three patients with melanoma indicate detection of the SLNs with acquisition times between 60 and 410 s with an injected activity of 26 MBq 99 mTc and prior localization with standard gamma camera lymphoscintigraphy. The laboratory performance of this imaging probe is limited by the pinhole collimator performance and the necessity of working in minification due to the limited detector size. However, in clinical operative conditions, the CdTe imaging probe was effective in detecting SLNs with adequate resolution and an acceptable sensitivity. Sensitivity is expected to improve with the future availability of a larger CdTe detector permitting operation at shorter distances from the patient skin.

Critical exponent analysis of lightly germanium-doped La0.7Ca0.3Mn1-xGexO3 (x = 0.05 and x = 0.07)

NASA Astrophysics Data System (ADS)

Nanto, Dwi; Kurniawan, Budhy; Soegijono, Bambang; Ghosh, Nilotpal; Hwang, Jong-Soon; Yu, Seong-Cho

2018-04-01

We have used a critical behavior study of La0.7Ca0.3MnO3 (LCMO) manganite perovskites whose Mn sites have been doped with Ge to explore magnetic interactions. Light Ge doping of 5 or 7 percent tended to produce LCMOs with second order magnetic transitions. The critical parameters of 5- and 7-percent Ge-doped LCMO were determined to be TC = 185 K, β = 0.331 ± 0.019, and γ = 1.15 ± 0.017; and TC = 153 K, β = 0.496 ± 0.011, and γ = 1.03 ± 0.046, respectively, via the modified Arrott plot method. Isothermal magnetization data collected near the Curie temperature (TC) was split into a universal function with two branches M(H,ɛ) = |ɛ|βf±(H/|ɛ|β+γ), where ɛ=(T-TC)/TC is the reduced temperature. f+ is used when T>TC, while f̲ is used when T

Pharmacokinetics and Pharmacodynamics of Curcumin in regulating anti-inflammatory and epigenetic gene expression.

PubMed

Boyanapalli, Sarandeep S S; Huang, Ying; Su, Zhengyuan; Cheng, David; Zhang, Chengyue; Guo, Yue; Rao, Rohit; Androulakis, Ioannis P; Kong, Ah-Ng

2018-06-05

Chronic inflammation is a key driver of cancer development. Nitrite levels, which are regulated by inducible nitric oxide synthase (iNOS), play a critical role in inflammation. While the anti-oxidant and anti-inflammatory effects of curcumin, a natural product present in the roots of Curcuma longa have been widely studied, the acute pharmacokinetics (PK) and pharmacodynamics (PD) of curcumin in suppressing pro-inflammatory markers and epigenetic modulators remain unclear. In this study, we evaluated the PK and PD of curcumin-induced suppression of lipopolysaccharide (LPS)-mediated inflammation in rat lymphocytes. LPS was administered intravenously either alone or with curcumin to female Sprague-Dawley rats. Plasma samples were analyzed for curcumin concentration and mRNA expression was quantified in lymphocytes. Relative gene expression of several inflammatory and epigenetic modulators was analyzed. To investigate the relationship between curcumin concentration and iNOS, TNF-α, and IL-6 gene expression, PK/PD modeling using Jusko's indirect response model (IDR) integrating transit compartments (TC) describing the delayed response was conducted. The concentration-time profile of curcumin exhibited a bi-exponential decline, which was well described by a two-compartmental pharmacokinetic model. Importantly our results demonstrate that LPS induced gene expression of pro-inflammatory markers in lymphocytes, with peak expression at approximately 3 h and curcumin suppressed the gene expression in animals administered with LPS. These effects were well captured using the IDR model and an IDR model with the transit compartments. In summary, the PK/PD modeling approach could potentially provide a robust quantitative framework for evaluating the acute anti-inflammatory and epigenetic effects of curcumin in future clinical trials. This article is protected by copyright. All rights reserved.

Life Path as a Predictor of Performance in the Navy: A Longitudinal Study.

DTIC Science & Technology

1980-04-01

learning came easy to me. Q103. Write letters. o Reading Q 36. I spent a lot of time in the library . Q 45. I was a good reader when I was in high school...Q 50. I could read when I entered first grade. Q 81. I spent a lot of my time reading. Q102. Go to libraries . Q104 . Read newspapers. Q115. Read...Bought my first car Personal Competence V37 Time in library V46 Good reader V51 Read when entered first grade(- V105 Went boating (-) V124 Read

Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1-Selected Advanced Non-Small-Cell Lung Cancer (BIRCH).

PubMed

Peters, Solange; Gettinger, Scott; Johnson, Melissa L; Jänne, Pasi A; Garassino, Marina C; Christoph, Daniel; Toh, Chee Keong; Rizvi, Naiyer A; Chaft, Jamie E; Carcereny Costa, Enric; Patel, Jyoti D; Chow, Laura Q M; Koczywas, Marianna; Ho, Cheryl; Früh, Martin; van den Heuvel, Michel; Rothenstein, Jeffrey; Reck, Martin; Paz-Ares, Luis; Shepherd, Frances A; Kurata, Takayasu; Li, Zhengrong; Qiu, Jiaheng; Kowanetz, Marcin; Mocci, Simonetta; Shankar, Geetha; Sandler, Alan; Felip, Enriqueta

2017-08-20

Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy. Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5% of TC or IC (TC2/3 or IC2/3 [TC or IC ≥ 5% PD-L1-expressing cells, respectively]) were enrolled. Atezolizumab 1,200 mg was administered intravenously every 3 weeks. Efficacy-evaluable patients (N = 659) comprised three cohorts: first line (cohort 1; n = 139); second line (cohort 2; n = 268); and third line or higher (cohort 3; n = 252). The primary end point was independent review facility-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Secondary end points included median duration of response, progression-free survival, and overall survival (OS). Results BIRCH met its primary objective of demonstrating a significant ORR versus historical controls. With a minimum of 12 months of follow-up, the independent review facility-assessed ORR was 18% to 22% for the three cohorts, and 26% to 31% for the TC3 or IC3 subgroup; most responses are ongoing. Responses occurred regardless of EGFR or KRAS mutation status. The median OS from an updated survival analysis (minimum of 20 month follow up) for cohort 1 was 23.5 months (26.9 months for TC3 or IC3 patients); the median OS in cohorts 2 and 3 was 15.5 and 13.2 months, respectively. The safety profile was similar across cohorts and consistent with previous atezolizumab monotherapy trials. Conclusion BIRCH demonstrated responses with atezolizumab monotherapy in patients with PD-L1-selected advanced NSCLC, with good tolerability. PD-L1 status may serve as a predictive biomarker for identifying patients most likely to benefit from atezolizumab.

Tubulocystic Carcinoma of the Kidney with Poorly Differentiated Foci: A Frequent Morphologic Pattern of Fumarate Hydratase-Deficient Renal Cell Carcinoma

PubMed Central

Smith, Steven C; Trpkov, Kiril; Chen, Ying-Bei; Mehra, Rohit; Sirohi, Deepika; Ohe, Chisato; Cani, Andi K; Hovelson, Daniel H; Omata, Kei; McHugh, Jonathan B; Jochum, Wolfram; Colecchia, Maurizio; Amin, Mitual; Divatia, Mukul K; Hes, Ondřej; Menon, Santosh; da Cunha, Isabela Werneck; Tripodi, Sergio; Brimo, Fadi; Gill, Anthony J; Osunkoya, Adeboye O; Magi-Galluzzi, Cristina; Sibony, Mathilde; Williamson, Sean R; Nesi, Gabriella; Picken, Maria M; Maclean, Fiona; Agaimy, Abbas; Cheng, Liang; Epstein, Jonathan I; Reuter, Victor E; Tickoo, Satish K; Tomlins, Scott A; Amin, Mahul B

2017-01-01

An emerging group of high grade renal cell carcinomas (RCCs), particularly carcinomas arising in the hereditary leiomyomatosis renal cell carcinoma syndrome (HLRCC), show fumarate hydratase (FH) gene mutation and loss of function. Based on similar cytomorphology and clinicopathologic features between these tumors and cases described as tubulocystic carcinomas with poorly differentiated foci of infiltrative adenocarcinoma (TC-PD), we hypothesized a relationship between these entities. First, 29 RCCs with morphology of TC-PD were identified retrospectively and assessed for FH expression and aberrant succination (2SC) by immunohistochemistry (IHC), with targeted next generation sequencing (NGS) of 409 genes—including FH—performed on a subset. The 29 TC-PD RCCs included 21 males and 8 females, aged 16-86 years (median 46), with tumors measuring 3-21 cm (median 9) arising in the right (n=16) and left (n=13) kidneys. Family history or stigmata of HLRCC were identified in only 3 (12%). These tumors were aggressive, with 79% showing perinephric extension, nodal involvement in 41%, and metastasis in 86%. Of these, 16 (55%) demonstrated loss of FH by IHC (14/14 with positive 2SC). In contrast, 5 (17%) showed a wild type immunoprofile of FH+/2SC-. An intriguing group of 8 (28%) showed variable FH± positivity, but with strong/diffuse 2SC+. NGS revealed 8 cases with FH mutations, including 5 FH-/2SC+ and 3 FH±/2SC+ cases, but none in FH+/2SC- cases. Secondly, we retrospectively reviewed the morphology of two well-characterized cohorts of RCCs with FH-deficiency determined by IHC or sequencing (n=23 and n=9), unselected for TC-PD pattern, identifying the TC-PD morphology in 10 (31%). We conclude that RCCs with TC-PD morphology are enriched for FH deficiency, and we recommend additional work up, including referral to genetic counseling, for prospective cases. Additionally, based on these and other observations, we propose the term “FH-deficient RCC” as a provisional term for tumors with a combination of suggestive morphology and immunophenotype but where genetic confirmation is unavailable upon diagnosis. This term will serve as a provisional nomenclature that will enable triage of individual cases for genetic counseling and testing, while designating these cases for prospective studies of their relationship to HLRCC. PMID:27635946

40 CFR 33.202 - How does an entity qualify as an MBE or WBE under EPA's 8% statute?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Indian tribes and Alaska Native Corporations; 13 CFR 124.110 for special rules applicable to Native... 124.103; see also 13 CFR 124.109 for special rules applicable to Indian tribes and Alaska Native... regulations (13 CFR 124.104). (See also 13 CFR 124.109 for special rules applicable to Indian tribes and...

Radiochemical studies of 99mTc complexes of modified cysteine ligands and bifunctional chelating agents.

PubMed

Pillai, M R; Kothari, K; Banerjee, S; Samuel, G; Suresh, M; Sarma, H D; Jurisson, S

1999-07-01

The synthesis of four novel ligands using the amino-acid cysteine and its ethyl carboxylate derivative is described. The synthetic method involves a two-step procedure, wherein the intermediate Schiff base formed by the condensation of the amino group of the cysteine substrate and salicylaldehyde is reduced to give the target ligands. The intermediates and the final products were characterized by high resolution nuclear magnetic resonance spectroscopy. Complexation studies of the ligands with 99mTc were optimized using stannous tartrate as the reducing agent under varying reaction conditions. The complexes were characterized using standard quality control techniques such as thin layer chromatography, paper electrophoresis, and paper chromatography. Lipophilicities of the complexes were estimated by solvent extraction into chloroform. Substantial changes in net charge and lipophilicity of the 99mTc complexes were observed on substituting the carboxylic acid functionality in ligands I and II with the ethyl carboxylate groups (ligands II and IV). All the ligands formed 99mTc complexes in high yield. Whereas the complexes with ligands I and II were observed to be hydrophilic in nature and not extractable into CHCl3, ligands III and IV resulted in neutral and lipophilic 99mTc complexes. The 99mTc complex with ligand II was not stable and on storage formed a hydrophilic and nonextractable species. The biodistribution of the complexes of ligands I and II showed that they cleared predominantly through the kidneys, whereas the complexes with ligands III and IV were excreted primarily through the hepatobiliary system. No significant brain uptake was observed with the 99mTc complexes with ligands III and IV despite their favorable properties of neutrality, lipophilicity, and conversion into a hydrophilic species. These ligands offer potential for use as bifunctional chelating agents.

The difference of scoring dose to water or tissues in Monte Carlo dose calculations for low energy brachytherapy photon sources.

PubMed

Landry, Guillaume; Reniers, Brigitte; Pignol, Jean-Philippe; Beaulieu, Luc; Verhaegen, Frank

2011-03-01

The goal of this work is to compare D(m,m) (radiation transported in medium; dose scored in medium) and D(w,m) (radiation transported in medium; dose scored in water) obtained from Monte Carlo (MC) simulations for a subset of human tissues of interest in low energy photon brachytherapy. Using low dose rate seeds and an electronic brachytherapy source (EBS), the authors quantify the large cavity theory conversion factors required. The authors also assess whether ap plying large cavity theory utilizing the sources' initial photon spectra and average photon energy induces errors related to spatial spectral variations. First, ideal spherical geometries were investigated, followed by clinical brachytherapy LDR seed implants for breast and prostate cancer patients. Two types of dose calculations are performed with the GEANT4 MC code. (1) For several human tissues, dose profiles are obtained in spherical geometries centered on four types of low energy brachytherapy sources: 125I, 103Pd, and 131Cs seeds, as well as an EBS operating at 50 kV. Ratios of D(w,m) over D(m,m) are evaluated in the 0-6 cm range. In addition to mean tissue composition, compositions corresponding to one standard deviation from the mean are also studied. (2) Four clinical breast (using 103Pd) and prostate (using 125I) brachytherapy seed implants are considered. MC dose calculations are performed based on postimplant CT scans using prostate and breast tissue compositions. PTV D90 values are compared for D(w,m) and D(m,m). (1) Differences (D(w,m)/D(m,m)-1) of -3% to 70% are observed for the investigated tissues. For a given tissue, D(w,m)/D(m,m) is similar for all sources within 4% and does not vary more than 2% with distance due to very moderate spectral shifts. Variations of tissue composition about the assumed mean composition influence the conversion factors up to 38%. (2) The ratio of D90(w,m) over D90(m,m) for clinical implants matches D(w,m)/D(m,m) at 1 cm from the single point sources, Given the small variation with distance, using conversion factors based on the emitted photon spectrum (or its mean energy) of a given source introduces minimal error. The large differences observed between scoring schemes underline the need for guidelines on choice of media for dose reporting. Providing such guidelines is beyond the scope of this work.

Oxidation of methionine - is it limiting the diagnostic properties of 99mTc-labeled Exendin-4, a Glucagon-Like Peptide-1 receptor agonist?

PubMed

Janota, Barbara; Karczmarczyk, Urszula; Laszuk, Ewa; Garnuszek, Piotr; Mikołajczak, Renata

2016-01-01

Preliminary clinical evaluation of 99mTc-EDDA/HYNIC-Met14-Exendin-4 showed that the complex offers new diagnostic possibilities for insulinoma and MTC. Exendin-4 contains methionine at position 14 in the amino acid chain, which may be oxidized to methionine sulfoxide and, from the pharmaceutical point of view, the oxidized moiety becomes an undesired impurity in the final radioactive preparation. Therefore, the aim of this study was to investigate the influence of commonly used methods to eliminate the effect of methionine oxidation in peptides, i.e. the replacement of methionine by norleucine (Nle) and the addition of L-methionine, on the in vitro stability and the biodistribution. 99mTc-EDDA/HYNIC-Met14-Exendin-4, 99mTc-EDDA/HYNIC-Nle14-Exendin-4, 99mTc-EDDA/HYNIC-Met14-Ex-endin-4 with the addition of L-methionine and an oxidized form of Exendin-4, i.e. 99mTc-EDDA/HYNIC-Met14(ox)-Exendin-4 were compared in vivo with 68Ga-NODAGA-Nle14-Exendin-4 in normal Wistar rats. The stability and lipophilicity were determined in vitro. Biodistribution studies confirmed the specific uptake of all tested complexes in the GLP-1 positive organs: lungs, pancreas and stomach. The uptake of 99mTc-EDDA/HYNIC-Met14-Exendin-4 with the addition of L-methionine and for 68Ga-NODAGA-Nle14-Exendin-4 at 1h p.i. was around 2-fold higher than that of 99mTc-EDDA/HYNIC-Met14-Exendin-4 and 99mTc-EDDA/HYNIC-Nle14-Exendin-4. Although the substitution of methionine by norleucine in the HYNIC-Exendin-4 did not result in improved bio-distribution, the use of L-methionine, as the excipient that inhibits the oxidation of methionine in the peptide chain resulted in higher lung/blood and stomach/blood uptake ratios. Our results confirmed that methionine at position 14 of amino acid chain of Exendin-4 plays an important role in the interaction with GLP-1 receptor positive tissue.

PET imaging of β-glucuronidase activity by an activity-based 124I-trapping probe for the personalized glucuronide prodrug targeted therapy.

PubMed

Su, Yu-Cheng; Cheng, Ta-Chun; Leu, Yu-Ling; Roffler, Steve R; Wang, Jaw-Yuan; Chuang, Chih-Hung; Kao, Chien-Han; Chen, Kai-Chuan; Wang, Hsin-Ell; Cheng, Tian-Lu

2014-12-01

Beta-glucuronidase (βG) is a potential biomarker for cancer diagnosis and prodrug therapy. The ability to image βG activity in patients would assist in personalized glucuronide prodrug cancer therapy. However, whole-body imaging of βG activity for medical usage is not yet available. Here, we developed a radioactive βG activity-based trapping probe for positron emission tomography (PET). We generated a (124)I-tyramine-conjugated difluoromethylphenol beta-glucuronide probe (TrapG) to form (124)I-TrapG that could be selectively activated by βG for subsequent attachment of (124)I-tyramine to nucleophilic moieties near βG-expressing sites. We estimated the specificity of a fluorescent FITC-TrapG, the cytotoxicity of tyramine-TrapG, and the serum half-life of (124)I-TrapG. βG targeting of (124)I-TrapG in vivo was examined by micro-PET. The biodistribution of (131)I-TrapG was investigated in different organs. Finally, we imaged the endogenous βG activity and assessed its correlation with therapeutic efficacy of 9-aminocamptothecin glucuronide (9ACG) prodrug in native tumors. FITC-TrapG showed specific trapping at βG-expressing CT26 (CT26/mβG) cells but not in CT26 cells. The native TrapG probe possessed low cytotoxicity. (124)I-TrapG preferentially accumulated in CT26/mβG but not CT26 cells. Meanwhile, micro-PET and whole-body autoradiography results demonstrated that (124)I-TrapG signals in CT26/mβG tumors were 141.4-fold greater than in CT26 tumors. Importantly, Colo205 xenografts in nude mice that express elevated endogenous βG can be monitored by using infrared glucuronide trapping probes (NIR-TrapG) and suppressed by 9ACG prodrug treatment. (124)I-TrapG exhibited low cytotoxicity allowing long-term monitoring of βG activity in vivo to aid in the optimization of prodrug targeted therapy. ©2014 American Association for Cancer Research.

Superconductivity and ferromagnetism in Pd doped Y9Co7

NASA Astrophysics Data System (ADS)

Klimczuk, Tomasz; Strychalska, Judyta; Thompson, Joe; Cava, Robert

The ferromagnetic superconductor Y9Co7 was chemically doped with Pd in an attempt to form Y9Co7-xPdx for 0

KSC-08pd1167

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialists Greg Chamitoff (left) and Akihiko Hoshide (center) and Commander Mark Kelly take part in M113 training on Launch Pad 39A. They and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1172

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Karen Nyberg is ready to begin driving practice in the M113 armored personnel carrier, part of emergency training. Behind her is Pilot Ken Ham. She and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1176

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Pilot Ken Ham stands ready to practice driving the M113 armored personnel carrier as part of emergency training. Behind him is Mission Specialist Karen Nyberg. Ham and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1169

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Ron Garan is ready to drive the M113 armored personnel carrier as part of emergency training. Behind him is Pilot Ken Ham. They and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1179

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Greg Chamitoff drives the M113 armored personnel carrier as part of emergency training. Behind him Commander Mark Kelly. At center is Battalion Chief George Hoggard providing supervision. Chamitoff and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

A systematic evaluation of the dose-rate constant determined by photon spectrometry for 21 different models of low-energy photon-emitting brachytherapy sources.

PubMed

Chen, Zhe Jay; Nath, Ravinder

2010-10-21

The aim of this study was to perform a systematic comparison of the dose-rate constant (Λ) determined by the photon spectrometry technique (PST) with the consensus value ((CON)Λ) recommended by the American Association of Physicists in Medicine (AAPM) for 21 low-energy photon-emitting interstitial brachytherapy sources. A total of 63 interstitial brachytherapy sources (21 different models with 3 sources per model) containing either (125)I (14 models), (103)Pd (6 models) or (131)Cs (1 model) were included in this study. A PST described by Chen and Nath (2007 Med. Phys. 34 1412-30) was used to determine the dose-rate constant ((PST)Λ) for each source model. Source-dependent variations in (PST)Λ were analyzed systematically against the spectral characteristics of the emitted photons and the consensus values recommended by the AAPM brachytherapy subcommittee. The values of (PST)Λ for the encapsulated sources of (103)Pd, (125)I and (131)Cs varied from 0.661 to 0.678 cGyh(-1) U(-1), 0.959 to 1.024 cGyh(-1)U(-1) and 1.066 to 1.073 cGyh(-1)U(-1), respectively. The relative variation in (PST)Λ among the six (103)Pd source models, caused by variations in photon attenuation and in spatial distributions of radioactivity among the source models, was less than 3%. Greater variations in (PST)Λ were observed among the 14 (125)I source models; the maximum relative difference was over 6%. These variations were caused primarily by the presence of silver in some (125)I source models and, to a lesser degree, by the variations in photon attenuation and in spatial distribution of radioactivity among the source models. The presence of silver generates additional fluorescent x-rays with lower photon energies which caused the (PST)Λ value to vary from 0.959 to 1.019 cGyh(-1)U(-1) depending on the amount of silver used by a given source model. For those (125)I sources that contain no silver, their (PST)Λ was less variable and had values within 1% of 1.024 cGyh(-1)U(-1). For the 16 source models that currently have an AAPM recommended (CON)Λ value, the agreement between (PST)Λ and (CON)Λ was less than 2% for 15 models and was 2.6% for 1 (103)Pd source model. Excellent agreement between (PST)Λ and (CON)Λ was observed for all source models that currently have an AAPM recommended consensus dose-rate constant value. These results demonstrate that the PST is an accurate and robust technique for the determination of the dose-rate constant for low-energy brachytherapy sources.

Peripheral dose measurements with diode and thermoluminescence dosimeters for intensity modulated radiotherapy delivered with conventional and un-conventional linear accelerator

PubMed Central

Kinhikar, Rajesh; Gamre, Poonam; Tambe, Chandrashekhar; Kadam, Sudarshan; Biju, George; Suryaprakash; Magai, C. S.; Dhote, Dipak; Shrivastava, Shyam; Deshpande, Deepak

2013-01-01

The objective of this paper was to measure the peripheral dose (PD) with diode and thermoluminescence dosimeter (TLD) for intensity modulated radiotherapy (IMRT) with linear accelerator (conventional LINAC), and tomotherapy (novel LINAC). Ten patients each were selected from Trilogy dual-energy and from Hi-Art II tomotherapy. Two diodes were kept at 20 and 25 cm from treatment field edge. TLDs (LiF:MgTi) were also kept at same distance. TLDs were also kept at 5, 10, and 15 cm from field edge. The TLDs were read with REXON reader. The readings at the respective distance were recorded for both diode and TLD. The PD was estimated by taking the ratio of measured dose at the particular distance to the prescription dose. PD was then compared with diode and TLD for LINAC and tomotherapy. Mean PD for LINAC with TLD and diode was 2.52 cGy (SD 0.69), 2.07 cGy (SD 0.88) at 20 cm, respectively, while at 25 cm, it was 1.94 cGy (SD 0.58) and 1.5 cGy (SD 0.75), respectively. Mean PD for tomotherapy with TLD and diode was 1.681 cGy SD 0.53) and 1.58 (SD 0.44) at 20 cm, respectively. The PD was 1.24 cGy (SD 0.42) and 1.088 cGy (SD 0.35) at 25 cm, respectively, for tomotherapy. Overall, PD from tomotherapy was found lower than LINAC by the factor of 1.2-1.5. PD measurement is essential to find out the potential of secondary cancer. PD for both (conventional LINAC) and novel LINACs (tomotherapy) were measured and compared with each other. The comparison of the values for PD presented in this work and those published in the literature is difficult because of the different experimental conditions. The diode and TLD readings were reproducible and both the detector readings were comparable. PMID:23531765

Visit-to-visit cholesterol variability correlates with coronary atheroma progression and clinical outcomes.

PubMed

Clark, Donald; Nicholls, Stephen J; St John, Julie; Elshazly, Mohamed B; Kapadia, Samir R; Tuzcu, E Murat; Nissen, Steven E; Puri, Rishi

2018-04-21

Utilizing serial intravascular ultrasonography (IVUS), we aimed to exam the association of intra-individual lipid variability, coronary atheroma progression, and clinical outcomes. We performed a post hoc patient-level analysis of nine clinical trials involving 4976 patients with coronary artery disease who underwent serial coronary IVUS in the setting of a range of medical therapies. We assessed the associations between progression in percent atheroma volume (ΔPAV), clinical outcomes, and visit-to-visit lipid variability including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC)/HDL-C, and apolipoprotein B (ApoB). Variability of lipid parameters was measured using intra-individual standard deviation over 3, 6, 12, 18, and 24 months. Atherogenic lipoprotein variability significantly associated with ΔPAV [odds ratio (95% confidence interval; P-value), LDL-C: 1.09 (1.02, 1.17, P = 0.01); non-HDL-C: 1.10 (1.02, 1.18, P = 0.01); TC/HDL-C: 1.14 (1.06, 1.24, P = 0.001); ApoB: 1.13 (1.03, 1.24, P = 0.01)]. Survival curves revealed significant stepwise relationships between cumulative major adverse cardiovascular events and increasing quartiles of atherogenic lipoprotein variability at 24-months follow-up (log-rank P < 0.01 for all lipoproteins except HDL-C). Stronger associations were noted between achieved lipoprotein levels and ΔPAV [LDL-C: 1.27 (1.17, 1.39; P < 0.001); non-HDL-C: 1.32 (1.21, 1.45; P < 0.001); TC/HDL-C: 1.31 (1.19, 1.45; P < 0.001); ApoB: 1.20 (1.07, 1.35; P = 0.003)]. Greater visit-to-visit variability in atherogenic lipoprotein levels significantly associates with coronary atheroma progression and clinical outcomes, although the association between achieved atherogenic lipoproteins and atheroma progression appears stronger. These data highlight the importance of achieving low and consistent atherogenic lipoprotein levels to promote plaque regression and improve clinical outcomes.

[Bifunctional chelates of Rh-105, Au-199, and other metallic radionuclides as potential radiotherapeutic agents

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

Not Available

1991-12-31

Progress during this period is reported under the following headings: Diethylenetriamine based and related bifunctional chelating agents and their complexation with Rh-105, Au-198, Pd-109, cu-67, In-111, and Co-57; studies of Pd-109, Rh-105 and Tc-99m with bifunctional chelates based on phenylenediamine; establishment of an appropriate protein assay method for conjugated proteins; studies of new bifunctional Bi, Tri and tetradentate amine oxime ligands with Rh-105; IgG and antibody B72.3 conjugation studies by HPLC Techniques with bifunctional metal chelates; and progress on ligand systems for Au(III).

(Bifunctional chelates of Rh-105, Au-199, and other metallic radionuclides as potential radiotherapeutic agents)

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

Not Available

1991-01-01

Progress during this period is reported under the following headings: Diethylenetriamine based and related bifunctional chelating agents and their complexation with Rh-105, Au-198, Pd-109, cu-67, In-111, and Co-57; studies of Pd-109, Rh-105 and Tc-99m with bifunctional chelates based on phenylenediamine; establishment of an appropriate protein assay method for conjugated proteins; studies of new bifunctional Bi, Tri and tetradentate amine oxime ligands with Rh-105; IgG and antibody B72.3 conjugation studies by HPLC Techniques with bifunctional metal chelates; and progress on ligand systems for Au(III).

[Effects of carbon components of fine particulate matter (PM2.5) on atherogenic index of plasma].

PubMed

Fan, Jiao; Qin, Xiaolei; Xue, Xiaodan; Han, Bin; Bai, Zhipeng; Tang, Naijun; Zhang, Liwen

2014-01-01

To evaluate associations between carbon constituents of fine particulate matter (PM2.5) and atherogenic index of plasma (AIP). We collected subjects from two communities by a system sampling, and 112 people aged over 60 years old without cardiovascular disease were recruited. The levels of cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) of objects, and personal exposure to PM2.5 were measured on December, 2011. Total carbon (TC), organic carbon (OC) and elemental carbon (EC) of PM2.5 were detected and AIP was calculated according to its definition. The value of AIP among the 112 subjects was 0.05 ± 0.26. Personal exposure concentration of PM2.5 and its carbon components (TC,OC and EC) were (164.75 ± 110.67), (53.86 ± 29.65), (44.93 ± 26.37) and (9.49 ± 5.75) µg/m(3), respectively. The Pearson analysis showed the linear relationship between TC,OC,EC and AIP, all significant positive correlations. The correlation coefficients were TC (r = 0.307, P < 0.05),OC (r = 0.287, P < 0.05) and EC (r = 0.252, P < 0.05), respectively. The multiple logistic regression analysis showed that when the AIP risk categories were selected as dependent variable and low risk group as reference group, the regression coefficient of TC,OC and EC was separately 1.03 (95%CI:1.01-1.05), 1.03 (95%CI:1.01-1.05), 1.12 (95%CI:1.02-1.22) in the high risk group; while there was no statistical significance of the regression coefficient and OR in the middle risk group. There was stable associations between the carbon constituents (TC,OC and EC) of fine Particulate Matter (PM2.5) and AIP. The findings suggested that carbon components of PM2.5 should be considered as risk factors of atherogenic.

Selective Interactions of Valeriana officinalis Extracts and Valerenic Acid with [H]Glutamate Binding to Rat Synaptic Membranes.

PubMed

Del Valle-Mojica, Lisa M; Ayala-Marín, Yoshira M; Ortiz-Sanchez, Carmen M; Torres-Hernández, Bianca A; Abdalla-Mukhaimer, Safa; Ortiz, José G

2011-01-01

Although GABA neurotransmission has been suggested as a mechanism for Valeriana officinalis effects, CNS depression can also be evoked by inhibition of ionotropic (iGluR) and metabotropic glutamate receptors (mGluR). In this study, we examined if aqueous valerian extract interacted with glutamatergic receptors. Freshly prepared aqueous valerian extract was incubated with rat cortical synaptic membranes in presence of 20 nM [(3)H]Glutamate. Aqueous valerian extract increased [(3)H]Glutamate binding from 1 × 10(-7) to 1 × 10(-3) mg/mL. In the presence of (2S,1'S,2'S)-2-(Carboxycyclopropyl)glycine (LCCG-I) and (2S,2'R,3'R)-2-(2',3'-Dicarboxycyclopropyl)glycine (DCG-IV), Group II mGluR agents, valerian extract markedly decreased [(3)H]Glutamate binding, while (2S)-2-amino-3-(3,5-dioxo-1,2,4-oxadiazolidin-2-yl) propanoic acid) (quisqualic acid, QA), Group I mGluR agonist, increased [(3)H]Glutamate binding. At 0.05 mg/mL aqueous valerian extract specifically interacted with kainic acid NMDA and AMPA receptors. Valerenic acid, a marker compound for Valeriana officinalis, increased the [(3)H]Glutamate binding after 1.6 × 10(-2) mg/mL, and at 0.008 mg/mL it interacted only with QA (Group I mGluR). The selective interactions of valerian extract and valerenic acid with Group I and Group II mGluR may represent an alternative explanation for the anxiolytic properties of this plant.

HDAC inhibitors enhance neratinib activity and when combined enhance the actions of an anti-PD-1 immunomodulatory antibody in vivo.

PubMed

Booth, Laurence; Roberts, Jane L; Poklepovic, Andrew; Avogadri-Connors, Francesca; Cutler, Richard E; Lalani, Alshad S; Dent, Paul

2017-10-27

Patients whose NSCLC tumors become afatinib resistant presently have few effective therapeutic options to extend their survival. Afatinib resistant NSCLC cells were sensitive to clinically relevant concentrations of the irreversible pan-HER inhibitor neratinib, but not by the first generation ERBB1/2/4 inhibitor lapatinib. In multiple afatinib resistant NSCLC clones, HDAC inhibitors reduced the expression of ERBB1/3/4, but activated c-SRC, which resulted in higher total levels of ERBB1/3 phosphorylation. Neratinib also rapidly reduced the expression of ERBB1/2/3/4, c-MET and of mutant K-/N-RAS; K-RAS co-localized with phosphorylated ATG13 and with cathepsin B in vesicles. Combined exposure of cells to [neratinib + HDAC inhibitors] caused inactivation of mTORC1 and mTORC2, enhanced autophagosome and subsequently autolysosome formation, and caused an additive to greater than additive induction of cell death. Knock down of Beclin1 or ATG5 prevented HDAC inhibitors or neratinib from reducing ERBB1/3/4 and K-/N-RAS expression and reduced [neratinib + HDAC inhibitor] lethality. Neratinib and HDAC inhibitors reduced the expression of multiple HDAC proteins via autophagy that was causal in the reduced expression of PD-L1, PD-L2 and ornithine decarboxylase, and increased expression of Class I MHCA. In vivo , neratinib and HDAC inhibitors interacted to suppress the growth of 4T1 mammary tumors, an effect that was enhanced by an anti-PD-1 antibody. Our data support the premises that neratinib lethality can be enhanced by HDAC inhibitors, that neratinib may be a useful therapeutic tool in afatinib resistant NSCLC, and that [neratinib + HDAC inhibitor] exposure facilitates anti-tumor immune responses.

HDAC inhibitors enhance neratinib activity and when combined enhance the actions of an anti-PD-1 immunomodulatory antibody in vivo

PubMed Central

Booth, Laurence; Roberts, Jane L.; Poklepovic, Andrew; Avogadri-Connors, Francesca; Cutler, Richard E.; Lalani, Alshad S.; Dent, Paul

2017-01-01

Patients whose NSCLC tumors become afatinib resistant presently have few effective therapeutic options to extend their survival. Afatinib resistant NSCLC cells were sensitive to clinically relevant concentrations of the irreversible pan-HER inhibitor neratinib, but not by the first generation ERBB1/2/4 inhibitor lapatinib. In multiple afatinib resistant NSCLC clones, HDAC inhibitors reduced the expression of ERBB1/3/4, but activated c-SRC, which resulted in higher total levels of ERBB1/3 phosphorylation. Neratinib also rapidly reduced the expression of ERBB1/2/3/4, c-MET and of mutant K-/N-RAS; K-RAS co-localized with phosphorylated ATG13 and with cathepsin B in vesicles. Combined exposure of cells to [neratinib + HDAC inhibitors] caused inactivation of mTORC1 and mTORC2, enhanced autophagosome and subsequently autolysosome formation, and caused an additive to greater than additive induction of cell death. Knock down of Beclin1 or ATG5 prevented HDAC inhibitors or neratinib from reducing ERBB1/3/4 and K-/N-RAS expression and reduced [neratinib + HDAC inhibitor] lethality. Neratinib and HDAC inhibitors reduced the expression of multiple HDAC proteins via autophagy that was causal in the reduced expression of PD-L1, PD-L2 and ornithine decarboxylase, and increased expression of Class I MHCA. In vivo, neratinib and HDAC inhibitors interacted to suppress the growth of 4T1 mammary tumors, an effect that was enhanced by an anti-PD-1 antibody. Our data support the premises that neratinib lethality can be enhanced by HDAC inhibitors, that neratinib may be a useful therapeutic tool in afatinib resistant NSCLC, and that [neratinib + HDAC inhibitor] exposure facilitates anti-tumor immune responses. PMID:29163826

Gamma camera dual imaging with a somatostatin receptor and thymidine kinase after gene transfer with a bicistronic adenovirus in mice.

PubMed

Zinn, Kurt R; Chaudhuri, Tandra R; Krasnykh, Victor N; Buchsbaum, Donald J; Belousova, Natalya; Grizzle, William E; Curiel, David T; Rogers, Buck E

2002-05-01

To compare two systems for assessing gene transfer to cancer cells and xenograft tumors with noninvasive gamma camera imaging. A replication-incompetent adenovirus encoding the human type 2 somatostatin receptor (hSSTr2) and the herpes simplex virus thymidine kinase (TK) enzyme (Ad-hSSTr2-TK) was constructed. A-427 human lung cancer cells were infected in vitro and mixed with uninfected cells at different ratios. A-427 tumors in nude mice (n = 23) were injected with 1 x 10(6) to 5 x 10(8) plaque-forming units (pfu) of Ad-hSSTr2-TK. The expressed hSSTr2 and TK proteins were imaged owing to internally bound, or trapped, technetium 99m ((99m)Tc)-labeled hSSTr2-binding peptide (P2045) and radioiodinated 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-5-iodouracil (FIAU), respectively. Iodine 125 ((125)I)-labeled FIAU was used in vitro and iodine 131 ((131)I)-labeled FIAU, in vivo. The (99m)Tc-labeled P2045 and (125)I- or (131)I-labeled FIAU were imaged simultaneously with different window settings with an Anger gamma camera. Treatment effects were tested with analysis of variance. Infected cells in culture trapped (125)I-labeled FIAU and (99m)Tc-labeled P2045; uptake correlated with the percentage of Ad-hSSTr2-TK-positive cells. For 100% of infected cells, 24% +/- 0.4 (mean +/- SD) of the added (99m)Tc-labeled P2045 was trapped, which is significantly lower (P <.05) than the 40% +/- 2 of (125)I-labeled FIAU that was trapped. For the highest Ad-hSSTr2-TK tumor dose (5 x 10(8) pfu), the uptake of (99m)Tc-labeled P2045 was 11.1% +/- 2.9 of injected dose per gram of tumor (thereafter, dose per gram), significantly higher (P <.05) than the uptake of (131)I-labeled FIAU at 1.6% +/- 0.4 dose per gram. (99m)Tc-labeled P2045 imaging consistently depicted hSSTr2 gene transfer in tumors at all adenovirus doses. Tumor uptake of (99m)Tc-labeled P2045 positively correlated with Ad-hSSTr2-TK dose; (131)I-labeled FIAU tumor uptake did not correlate with vector dose. The hSSTr2 and TK proteins were simultaneously imaged following dual gene transfer with an adenovirus vector. Copyright RSNA, 2002

99mTc-labeled PSMA inhibitor: Biokinetics and radiation dosimetry in healthy subjects and imaging of prostate cancer tumors in patients.

PubMed

Santos-Cuevas, Clara; Davanzo, Jenny; Ferro-Flores, Guillermina; García-Pérez, Francisco O; Ocampo-García, Blanca; Ignacio-Alvarez, Eleazar; Gómez-Argumosa, Edgar; Pedraza-López, Martha

2017-09-01

The prostate-specific membrane antigen (PSMA) is expressed in epithelial cells of the prostate and highly overexpressed in 95% of advanced prostate cancers. The aims of this study was to estimate the biokinetics and dosimetry of 99m Tc-EDDA/HYNIC-iPSMA ( 99m Tc-labeled PSMA inhibitor) in eight healthy subjects and evaluate its usefulness as a tumor-imaging agent in eight prostate cancer patients. 99m Tc-EDDA/HYNIC-iPSMA was obtained from a lyophilized formulation with radiochemical purities >98%, determined by reversed-phase HPLC and ITLC-SG analyses. Whole-body images from eight healthy subjects were acquired at 20min, and at 2, 6 and 24h after 99m Tc-EDDA/HYNIC-iPSMA administration. Regions of interest (ROIs) were drawn around the source organs on each time frame. Each ROI was corrected by background, attenuation, scattered radiation and physical decay. The image sequence was used to extrapolate the 99m Tc-EDDA/HYNIC-iPSMA time-activity curves of each organ to adjust the biokinetic model and calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation doses. In eight prostate cancer patients with histologically confirmed cancer, whole-body SPECT/CT images were obtained at 3h. The blood activity showed a half-life value of 4.98min for the fast component (T 1/2 α=ln2/8.34), 2.49h for the first slow component (T 1/2 β=ln2/0.278), and 9.24h for the second slow component (T 1/2 γ=ln2/0.076). Images from patients showed an average tumor/background ratio of 8.99±3.27 at 3h. The average equivalent doses calculated for a study using 740MBq were 3.80, 7.06, 9.69, 10.70, and 28.80mSv for the breast, spleen, salivary glands, liver, and kidneys respectively, with an effective dose of 3.42±0.78mSv. All the absorbed doses were comparable to those known for most of the 99m Tc studies. 99m Tc-EDDA/HYNIC-iPSMA obtained from kit formulations showed high tumor uptake in patients with malignant lesions, making it a promising imaging radiopharmaceutical to target site-specific prostate cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C.

PubMed

Dermaut, B; Seneca, S; Dom, L; Smets, K; Ceulemans, L; Smet, J; De Paepe, B; Tousseyn, S; Weckhuysen, S; Gewillig, M; Pals, P; Parizel, P; De Bleecker, J L; Boon, P; De Meirleir, L; De Jonghe, P; Van Coster, R; Van Paesschen, W; Santens, P

2010-01-01

m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. To determine the clinical-neurological spectrum and associated mutation loads in an extended m.14487T>C family. A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. Heteroplasmic m.14487T>C levels (36-52% in leucocytes, 97-99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

DNA as a Target for Anticancer Phen-Imidazole Pd(II) Complexes.

PubMed

Heydari, Maryam; Moghadam, Mahboube Eslami; Tarlani, AliAkbar; Farhangian, Hossein

2017-05-01

Imidazole ring is a known structure in many natural or synthetic drug molecules and its metal complexes can interact with DNA and do the cleavage. Hence, to study the influence of the structure and size of the ligand on biological behavior of metal complexes, two water-soluble Pd(II) complexes of phen and FIP ligands (where phen is 1,10-phenanthroline and FIP is 2-(Furan-2-yl)-1H-Imidazo[4,5-f][1, 10]phenanthroline) with the formula of [Pd(phen)(FIP)](NO 3 ) 2 and [Pd(FIP) 2 ]Cl 2 , that were activated against chronic myelogenous leukemia cell line, K562, were selected. Also, the interaction of these anticancer Pd(II) complexes with highly polymerized calf thymus DNA was extensively studied by means of electronic absorption, fluorescence, and circular dichroism in Tris-buffer. The results showed that the binding was positive cooperation and [Pd(phen)(FIP)](NO 3 ) 2 (K f  = 127 M -1 G = 1.2) exhibited higher binding constant and number of binding sites than [Pd(FIP) 2 ]Cl 2 (K f  = 13 M -1 G = 1.03) upon binding to DNA. The fluorescence data indicates that quenching effect for [Pd(phen)(FIP)](NO 3 ) 2 (K SV  = 58 mM -1 ) was higher than [Pd(FIP) 2 ]Cl 2 (K SV  = 12 mM -1 ). Also, [Pd(FIP) 2 ]Cl 2 interacts with ethidium bromide-DNA, as non-competitive inhibition, and can bind to DNA via groove binding and [Pd(phen)(FIP)](NO 3 ) 2 can intercalate in DNA. These results were confirmed by circular dichroism spectra. Docking data revealed that longer complexes have higher interaction energy and bind to DNA via groove binding. Graphical Abstract Two anticancer Pd(II) complexes of imidazole derivative have been synthesized and interacted with calf thymus DNA. Modes of binding have been studied by electronic absorption, fluorescence, and CD measurements. [Pd(FIP) 2 ]Cl 2 can bind to DNA via groove binding while intercalation mode of binding is observed for [Pd(phen)(FIP)](NO 3 ) 2 .

Factors affecting the sensitivity of Tc-99m methoxyisobutylisonitrile dual-phase parathyroid single photon emission computed tomography in primary hyperparathyroidism.

PubMed

Araz, Mine; Çayir, Derya; Erdoğan, Mehmet; Uçan, Bekir; Çakal, Erman

2017-02-01

The aim of this study was to investigate the effects of thyroid diseases and regularly used medications on the sensitivity of Tc-99m methoxyisobutylisonitrile (MIBI) dual-phase parathyroid single photon emission computed tomography (SPECT) and to define indicatives of the result of the study. Overall, 218 primary hyperparathyroidism patients (190 women, 28 men, mean age: 57±14 years) with thyroid-parathyroid ultrasonography and Tc-99m MIBI dual-phase parathyroid SPECT were retrospectively enrolled. Patients were divided as follows: a positive SPECT group [119 (54.6%) patients] and a negative SPECT group [99 (45.4%) patients]. The effects of thyroid diseases and use of calcium channel blockers, β-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, oral antidiabetics, thyroid hormone preparates, nonsteroidal anti-inflammatory drugs, and proton pump inhibitors on the sensitivity of Tc-99m MIBI dual-phase parathyroid SPECT were investigated. The frequency of NSAID usage was higher in the negative scan group (P<0.001). No significant difference was detected in terms of coexisting thyroid disease or usage of other medications. Overall sensitivity, specificity, positive, and negative predictive value of Tc-99m MIBI dual-phase parathyroid SPECT were calculated to be 89.6, 92.5, 94.1, and 86.9%. The sensitivity was low only in nonsteroidal anti-inflammatory drug users (75.6%) compared with nonusers (96.5%). Logistic regression showed that ultrasonography was indicative of a positive scan and the possibility of a negative result was increased by regular usage of nonsteroid anti-inflammatory drugs (odds ratio: 0.262, confidence interval: 0.128-0.538; P<0.001) CONCLUSION: Among various drug groups, NSAIDs may decrease the sensitivity of Tc-99m MIBI SPECT and, provided that these novel data are supported by other studies, patient preparation may be modified to stop NSAIDs before Tc-99m MIBI dual-phase parathyroid SPECT.

Atomic Energy Levels. As Derived From the Analyses of Optical Spectra. Volume 3

DTIC Science & Technology

1958-05-01

26756.70 0 1.24 1 27362. 55 1.06 10 1 .98626.50 1.443 S S 0 0 0 0 0 0 0 3® Mt --Coaniued Mo 1-Cmedaned Conf. De @al J Level Intera Oba. C;044 Del6 . J... De , 1 Level Inteval Ob, I Conig. Desig. J Level Interval Ob..g W 2 15. P7 L 146 83° 4 5M. 5 0 1.17 46’ S 51808.89 88 84’ 5 55957.80 1. 14 4w 6 51853...41772 --176.14 1.86 1 85&07 -14&.00 1.4041M4 728 10&3& 32 854 $2408. 07 165 4d0( GD)5 a 4D 31 10516. 34 1.44 4d$(a D)5p s ’ De 34 38560. 87 465. 33 L

KSC-08pd1719

NASA Image and Video Library

2008-06-14

CAPE CANAVERAL, Fla. – After their successful STS-124 mission and landing on Runway 15 at NASA's Kennedy Space Center, Mission Specialists Karen Nyberg and Akihiko Hoshide, Pilot Ken Ham and Mission Specialist Ron Garan are greeted by the Japan Aerospace Exploration Agency's Director of Program Management and Integration Yuichi Yamaura and Vice President Kaoru Mamiya, Center Director Bill Parsons and Associate Administrator for Space Operations Bill Gerstenmaier. Following Garan is Chief of the Astronaut Corps Stephen Lindsay and astronaut Janet Kavandi. Space shuttle Discovery's main landing gear touched down at 11:15:19 a.m. EDT on Runway 15. The nose landing gear touched down at 11:15:30 a.m. and wheel stop was at 11:16:19 a.m. The mission completed 5.7 million miles. The STS-124 mission delivered the Japan Aerospace Exploration Agency's large Japanese Pressurized Module and its remote manipulator system to the space station. Photo credit: NASA/Kim Shiflett

Surface Observation Climatic Summaries (SOCS) for Rickenbacker ANGB, Ohio

DTIC Science & Technology

1989-02-01

86.9 90.5 91.8 93.2 94.9 95.3 96.7 98.2 98.5 91.7 GE 103 72. 7 77 .’ 62. 1 86. 9 40.5 91.6 93. Z 94.9 95.3 96. 7 98.2 96. 5 93.7 1) () 0 71 o 77.9...I 95.’s 97.1 7. 6 97.7 97. 93.0 9.0 9.I1 98.1 9 ! 95.1 49.4 103 . 5 q7.7 Z33 1 hi.4 ml.s 95.6 9P.6 99.7 93.7 9R.7 98.7 9. 5 4 96.5 9;.1 98. t 99.7 95.9...19339 ;7. )0.2 3.3 63.4 63.6 63.7 )3. 7 63.7 53.7 ’,3.7 63.7 63.7 rF 103 . 57.5 5 .q 5 ". 5 ".4.3 64.1 64.2 𔃾._ A4.? 64.2 64.? 64.2 G C 00o 51.? 5 ,. 6

Development and Pharmacological Evaluation of New Bone-Targeted (99m)Tc-Radiolabeled Bisphosphonates.

PubMed

Makris, George; Tseligka, Eirini D; Pirmettis, Ioannis; Papadopoulos, Minas S; Vizirianakis, Ioannis S; Papagiannopoulou, Dionysia

2016-07-05

A novel bisphosphonate, 1-(3-aminopropylamino)ethane-1,1-diyldiphosphonic acid (3), was coupled to the tridentate chelators di-2-picolylamine, 2-picolylamine-N-acetic acid, iminodiacetic acid, 3-((2-aminoethyl)thio)-3-(1H-imidazol-4-yl)propanoic acid, and 2-((2-carboxyethyl)thio)-3-(1H-imidazol-4-yl)propanoic acid to form ligands 6, 9, 11, 15, and 19, respectively. Organometallic complexes of the general formula [Re/(99m)Tc(CO)3(κ(3)-L)] were synthesized, where L denotes ligand 6, 9, 11, 15, or 19. The rhenium complexes were prepared at the macroscopic level and characterized by spectroscopic methods. The technetium-99m organometallic complexes were synthesized in high yield and were identified by comparative reversed-phase HPLC with their Re analogues. The (99m)Tc tracers were stable in vitro and exhibited binding to hydroxyapatite. In biodistribution studies, all of the (99m)Tc complexes exhibited high bone uptake superior to that of 25, which is the directly (99m)Tc-labeled bisphosphonate 3, and comparable to that of (99m)Tc-methylene diphosphonate ((99m)Tc-MDP). The tracers [(99m)Tc(CO)3(6)] (26), [(99m)Tc(CO)3(9)] (27), [(99m)Tc(CO)3(11)] (28), and [(99m)Tc(CO)3(15)] (29) exhibited higher bone/blood ratios than (99m)Tc-MDP. 26 had the highest bone uptake at 1 h p.i. The new bisphosphonates showed no substantial growth inhibitory capacity in PC-3, Saos-2, and MCF-7 established cancer cell lines at low concentrations. Incubation of 26 with the same cancer cell lines indicated a rapid and saturated uptake. The promising properties of 26-29 indicate their potential for use as bone-imaging agents.

Technetium and Iodine Getters to Improve Cast Stone Performance

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

Qafoku, Nikolla; Neeway, James J.; Lawter, Amanda R.

2014-07-01

To determine the effectiveness of the various getter materials prior to their solidification in Cast Stone, a series of batch sorption experiments was performed at Pacific Northwest National Laboratory. To quantify the effectiveness of the removal of Tc(VII) and I(I) from solution by getters, the distribution coefficient, Kd (mL/g), was calculated. Testing involved placing getter material in contact with spiked waste solutions at a 1:100 solid-to-solution ratio for periods up to 45 days with periodic solution sampling. One Tc getter was also tested at a 1:10 solid-to-solution ratio. Two different solution media, 18.2 MΩ deionized water (DI H2O) and amore » 7.8 M Na LAW simulant, were used in the batch sorption tests. Each test was conducted at room temperature in an anoxic chamber containing N2 with a small amount of H2 (0.7%) to maintain anoxic conditions. Each getter-solution combination was run in duplicate. Three Tc- and I-doping concentrations were used separately in aliquots of both the 18.2 MΩ DI H2O and a 7.8 M Na LAW waste simulant. The 1× concentration was developed based on Hanford Tank Waste Operations Simulator (HTWOS) model runs to support the River Protection Project System Plan Revision 6. The other two concentrations were 5× and 10× of the HTWOS values. The Tc and I tests were run separately (i.e., the solutions did not contain both solutes). Sampling of the solid-solution mixtures occurred nominally after 0.2, 1, 3, 6, 9, 12, 15 days and ~35 to 45 days. Seven getter materials were tested for Tc and five materials were tested for I. The seven Tc getters were blast furnace slag 1 (BFS1) (northwest source), BFS2 (southeast source), Sn(II)-treated apatite, Sn(II) chloride, nano tin phosphate, KMS (a potassium-metal-sulfide), and tin hydroxapatite. The five iodine getters were layered bismuth hydroxide (LBH), argentite mineral, synthetic argentite, silver-treated carbon, and silver-treated zeolite. The Tc Kd values measured from experiments conducted using the 7.8 M Na LAW simulant (the simulant selected to represent LAW) for the first 15 days for four Tc getters (BFS1, BFS2, Sn(II)-treated apatite, and Sn(II) chloride) show no, to a very small, capacity to remove Tc from the LAW simulant. For the Tc-getter experiments in the 7.8 M LAW simulant, the majority of the effluent samples show very small drops in Tc concentrations for the 35-day compared to the 15-day samplings. However, the Tc concentration in the simulant blanks also dropped slightly during this period, so the effect of the getter contacting LAW simulant at 35 days compared to 15 days is minimal; except that the BFS1 1:10 test shows a slow but steady decrease in Tc concentration in the LAW simulant supernatant from the beginning to the 35 day contact at which point about 20% of the original Tc has been removed from solution. Lastly, the KMS getter gives the highest Kd value for Tc at 35 days where Kd values have increased to 104 mL/g. When considering the different I getters reacting with the 7.8 M LAW simulant, two getters are much more effective than the others: Ag zeolite and Syn Arg. The other getters have calculated iodide distribution coefficients that show very limited effectiveness in the caustic conditions created by the LAW simulant. These are preliminary results that will need more detailed analyses including both pre- and post-batch sorption getter solid-phase characterization using state-of-the-art instrumentation such as synchrotron X ray absorption spectroscopy, which can delineate the oxidation state of the Tc and likely iodine species as well as some of the getters key major components, sulfur and iron in the BFS, and tin and sulfur in the tin-bearing and sulfur-bearing getters. This report also describes future experimental studies to be performed to better elucidate the mechanisms controlling the Tc and I sequestration processes in the various getters and leach tests of getter-bearing Cast Stone monoliths.« less

Technetium and Iodine Getters to Improve Cast Stone Performance

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

Qafoku, Nikolla; Neeway, James J.; Lawter, Amanda R.

2015-02-19

To determine the effectiveness of the various getter materials prior to their solidification in Cast Stone, a series of batch sorption experiments was performed at Pacific Northwest National Laboratory. To quantify the effectiveness of the removal of Tc(VII) and I(I) from solution by getters, the distribution coefficient, K d (mL/g), was calculated. Testing involved placing getter material in contact with spiked waste solutions at a 1:100 solid-to-solution ratio for periods up to 45 days with periodic solution sampling. One Tc getter was also tested at a 1:10 solid-to-solution ratio. Two different solution media, 18.2 MΩ deionized water (DI H 2O)more » and a 7.8 M Na LAW simulant, were used in the batch sorption tests. Each test was conducted at room temperature in an anoxic chamber containing N2 with a small amount of H 2 (0.7%) to maintain anoxic conditions. Each getter-solution combination was run in duplicate. Three Tc- and I-doping concentrations were used separately in aliquots of both the 18.2 MΩ DI H2O and a 7.8 M Na LAW waste simulant. The 1× concentration was developed based on Hanford Tank Waste Operations Simulator (HTWOS) model runs to support the River Protection Project System Plan Revision 6. The other two concentrations were 5× and 10× of the HTWOS values. The Tc and I tests were run separately (i.e., the solutions did not contain both solutes). Sampling of the solid-solution mixtures occurred nominally after 0.2, 1, 3, 6, 9, 12, 15 days and ~35 to 45 days. Seven getter materials were tested for Tc and five materials were tested for I. The seven Tc getters were blast furnace slag 1 (BFS1) (northwest source), BFS2 (southeast source), Sn(II)-treated apatite, Sn(II) chloride, nano tin phosphate, KMS (a potassium-metal-sulfide), and tin hydroxapatite. The five iodine getters were layered bismuth hydroxide (LBH), argentite mineral, synthetic argentite, silver-treated carbon, and silver-treated zeolite. The Tc Kd values measured from experiments conducted using the 7.8 M Na LAW simulant (the simulant selected to represent LAW) for the first 15 days for four Tc getters (BFS1, BFS2, Sn(II)-treated apatite, and Sn(II) chloride) show no, to a very small, capacity to remove Tc from the LAW simulant. For the Tc-getter experiments in the 7.8 M LAW simulant, the majority of the effluent samples show very small drops in Tc concentrations for the 35-day compared to the 15-day samplings. However, the Tc concentration in the simulant blanks also dropped slightly during this period, so the effect of the getter contacting LAW simulant at 35 days compared to 15 days is minimal; except that the BFS1 1:10 test shows a slow but steady decrease in Tc concentration in the LAW simulant supernatant from the beginning to the 35 day contact at which point about 20% of the original Tc has been removed from solution. Lastly, the KMS getter gives the highest K d value for Tc at 35 days where K d values have increased to 104 mL/g. When considering the different I getters reacting with the 7.8 M LAW simulant, two getters are much more effective than the others: Ag zeolite and Syn Arg. The other getters have calculated iodide distribution coefficients that show very limited effectiveness in the caustic conditions created by the LAW simulant. These are preliminary results that will need more detailed analyses including both pre- and post-batch sorption getter solid-phase characterization using state-of-the-art instrumentation such as synchrotron X-ray absorption spectroscopy, which can delineate the oxidation state of the Tc and likely iodine species as well as some of the getters key major components, sulfur and iron in the BFS, and tin and sulfur in the tin-bearing and sulfur-bearing getters. This report also describes future experimental studies to be performed to better elucidate the mechanisms controlling the Tc and I sequestration processes in the various getters and leach tests of getter-bearing Cast Stone monoliths.« less

Recoil distance lifetime measurements in 122,124Xe

NASA Astrophysics Data System (ADS)

Govil, I. M.; Kumar, A.; Iyer, H.; Li, H.; Garg, U.; Ghugre, S. S.; Johnson, T.; Kaczarowski, R.; Kharraja, B.; Naguleswaran, S.; Walpe, J. C.

1998-02-01

Lifetimes of the lower-excited states in 122,124Xe are measured using the recoil-distance Doppler-shift technique. The reactions 110Pd(16O,4n)122Xe and 110Pd(18O,4n)124Xe at a beam energy of 66 MeV were used for this experiment. The lifetimes of the 2+, 4+, 6+, and 8+ states of the ground state band were extracted using the computer code LIFETIME including the corrections due to the side feeding and the nuclear deorientation effects. The lifetime of the 2+ state in 122Xe agrees with the recoil distance method (RDM) measurements but for the 124Xe it does not agree with the RDM measurements but agrees with the Coulomb-excitation experiment. The measured B(E2) values for both the nuclei are compared with the standard algebraic and the multishell models.

Colonic Oxidative and Mitochondrial Function in Parkinson's Disease and Idiopathic REM Sleep Behavior Disorder.

PubMed

Morén, C; González-Casacuberta, Í; Navarro-Otano, J; Juárez-Flores, D; Vilas, D; Garrabou, G; Milisenda, J C; Pont-Sunyer, C; Catalán-García, M; Guitart-Mampel, M; Tobías, E; Cardellach, F; Valldeoriola, F; Iranzo, A; Tolosa, E

2017-01-01

To determine potential mitochondrial and oxidative alterations in colon biopsies from idiopathic REM sleep behavior disorder (iRBD) and Parkinson's disease (PD) subjects. Colonic biopsies from 7 iRBD subjects, 9 subjects with clinically diagnosed PD, and 9 healthy controls were homogenized in 5% w/v mannitol. Citrate synthase (CS) and complex I (CI) were analyzed spectrophotometrically. Oxidative damage was assessed either by lipid peroxidation, through malondialdehyde and hydroxyalkenal content by spectrophotometry, or through antioxidant enzyme levels of superoxide dismutase-2 (SOD2), glutathione peroxidase-1 (Gpx1), and catalase (CAT) by western blot. The presence of mitochondrial DNA (mtDNA) deletions was assessed by long PCR and electrophoresis. Nonsignificant trends to CI decrease in both iRBD (45.69 ± 18.15; 23% decrease) and PD patients (37.57 ± 12.41; 37% decrease) were found compared to controls (59.51 ± 12.52, p : NS). Lipid peroxidation was maintained among groups (iRBD: 27.46 ± 3.04, PD: 37.2 ± 3.92, and controls: 31.71 ± 3.94; p : NS). Antioxidant enzymes SOD2 (iRBD: 2.30 ± 0.92, PD: 1.48 ± 0.39, and controls: 1.09 ± 0.318) and Gpx1 (iRBD 0.29 ± 0.12, PD: 0.56 ± 0.33, and controls: 0.38 ± 0.16) did not show significant differences between groups. CAT was only detected in 2 controls and 1 iRBD subject. One iRBD patient presented a single mtDNA deletion.

The role of postoperative Tc-99m pertechnetate scintigraphy in estimation of remnant mass and prediction of successful ablation in patients with differentiated thyroid cancer.

PubMed

Ozdemir, Didem; Cuhaci, Fatma N; Ozdemir, Elif; Aydin, Cevdet; Ersoy, Reyhan; Turkolmez, Seyda; Cakir, Bekir

2016-06-01

Surgery and radioactive iodine (RAI) ablation constitute the mainstay of the treatment of differentiated thyroid carcinoma (DTC). In this study, we aimed to evaluate the diagnostic value of postoperative early Tc-99m pertechnetate scanning to detect remnant thyroid tissue and predict ablation success. DTC patients evaluated with postoperative Tc-99m pertechnetate scintigraphy and treated with RAI between January 2007 and December 2014 were recruited. The results of Tc-99m pertechnetate scanning were compared with therapeutic I-131 whole-body scanning (TxWBS) and diagnostic I-131 whole-body scanning (DxWBS) performed 6-9 months after RAI. There were 154 (21.5%) male and 563 (78.5%) female patients, with a mean age of 49.11±12.35 years. Postoperative Tc-99m pertechnetate scanning was positive in 499 patients (69.6%) and negative in 218 (30.4%) patients. There were 673 (93.9%) patients with a positive TxWBS scan and 44 (6.1%) patients with negative TxWBS scan. Considering TxWBS as the standard test, sensitivity, specificity, positive predictive value, and negative predictive value of Tc-99m pertechnetate scanning were 72.2, 70.5, 97.4, and 14.2%, respectively. DxWBS was positive in 57 (9.0%) and negative in 564 (91%) patients. Ablation dose was higher and preablation thyroglobulin was lower in patients with negative DxWBS (P=0.001 and 0.04, respectively). Overall, 171 (92.9%) of 184 patients with negative Tc-99m pertechnetate had negative DxWBS. Postoperative Tc-99m pertechnetate scintigraphy has a high positive predictive value to detect remnant tissue in patients with DTC. Although negative Tc-99m pertechnetate scanning does not indicate removal of all thyroid tissue, it is related to successful ablation in more than 90% of patients.

Ambient Dose Equivalent measured at the Instituto Nacional de Cancerología Department of Nuclear Medicine

NASA Astrophysics Data System (ADS)

Ávila, O.; Torres-Ulloa, C. L.; Medina, L. A.; Trujillo-Zamudio, F. E.; de Buen, I. Gamboa; Buenfil, A. E.; Brandan, M. E.

2010-12-01

Ambient dose equivalent values were determined in several sites at the Instituto Nacional de Cancerología, Departmento de Medicina Nuclear, using TLD-100 and TLD-900 thermoluminescent dosemeters. Additionally, ambient dose equivalent was measured at a corridor outside the hospitalization room for patients treated with 137Cs brachytherapy. Dosemeter calibration was performed at the Instituto Nacional de Investigaciones Nucleares, Laboratorio de Metrología, to known 137Cs gamma radiation air kerma. Radionuclides considered for this study are 131I, 18F, 67Ga, 99mTc, 111In, 201Tl and 137Cs, with main gamma energies between 93 and 662 keV. Dosemeters were placed during a five month period in the nuclear medicine rooms (containing gamma-cameras), injection corridor, patient waiting areas, PET/CT study room, hot lab, waste storage room and corridors next to the hospitalization rooms for patients treated with 131I and 137Cs. High dose values were found at the waste storage room, outside corridor of 137Cs brachytherapy patients and PET/CT area. Ambient dose equivalent rate obtained for the 137Cs brachytherapy corridor is equal to (18.51±0.02)×10-3 mSv/h. Sites with minimum doses are the gamma camera rooms, having ambient dose equivalent rates equal to (0.05±0.03)×10-3 mSv/h. Recommendations have been given to the Department authorities so that further actions are taken to reduce doses at high dose sites in order to comply with the ALARA principle (as low as reasonably achievable).

Cyclotron laboratory of the Institute for Nuclear Research and Nuclear Energy

NASA Astrophysics Data System (ADS)

Tonev, D.; Goutev, N.; Georgiev, L. S.

2016-06-01

An accelerator laboratory is presently under construction in Sofia at the Institute for Nuclear Research and Nuclear Energy, Bulgarian Academy of Sciences. The laboratory will use a TR24 type of cyclotron, which provides a possibility to accelerate a proton beam with an energy of 15 to 24 MeV and current of up to 0.4 mA. An accelerator with such parameters allows to produce a large variety of radioisotopes for development of radiopharmaceuticals. The most common radioisotopes that could be produced with such a cyclotron are PET isotopes like: 11C, 13N, 15O, 18F, 124I, 64Cu, 68Ge/68Ga, and SPECT isotopes like: 123I, 111In, 67Ga, 57Co, 99m Tc. Our aim is to use the cyclotron facility for research in the fields of radiopharmacy, radiochemistry, radiobiology, nuclear physics, solid state physics, applied research, new materials and for education in all these fields including nuclear energy. The building of the laboratory will be constructed nearby the Institute for Nuclear Research and Nuclear Energy and the cyclotron together with all the equipment needed will be installed there.

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

Gagne, Nolan L.; Leonard, Kara L.; Rivard, Mark J.

Purpose: Clinical optimization of Collaborative Ocular Melanoma Study (COMS) eye plaque brachytherapy is currently limited to tumor coverage, consensus prescription dosage, and dose calculations to ocular structures. The biologically effective dose (BED) of temporary brachytherapy treatments is a function of both chosen radionuclide R and implant duration T. This study endeavored to evaluate BED delivered to the tumor volume and surrounding ocular structures as a function of plaque position P, prescription dose, R, and T. Methods: Plaque-heterogeneity-corrected dose distributions were generated with MCNP5 for the range of currently available COMS plaques loaded with sources using three available low-energy radionuclides. Thesemore » physical dose distributions were imported into the PINNACLE{sup 3} treatment planning system using the TG-43 hybrid technique and used to generate dose volume histograms for a T = 7 day implant within a reference eye geometry including the ciliary body, cornea, eyelid, foveola, lacrimal gland, lens, optic disc, optic nerve, retina, and tumor at eight standard treatment positions. The equation of Dale and Jones was employed to create biologically effective dose volume histograms (BEDVHs), allowing for BED volumetric analysis of all ROIs. Isobiologically effective prescription doses were calculated for T = 5 days down to 0.01 days, with BEDVHs subsequently generated for all ROIs using correspondingly reduced prescription doses. Objective functions were created to evaluate the BEDVHs as a function of R and T. These objective functions are mathematically accessible and sufficiently general to be applied to temporary or permanent brachytherapy implants for a variety of disease sites. Results: Reducing T from 7 to 0.01 days for a 10 mm plaque produced an average BED benefit of 26%, 20%, and 17% for {sup 103}Pd, {sup 125}I, and {sup 131}Cs, respectively, for all P; 16 and 22 mm plaque results were more position-dependent. {sup 103}Pd produced a 16%-35% BED benefit over {sup 125}I, whereas {sup 131}Cs produced a 3%-7% BED detriment, independent of P, T, and plaque size. Additionally, corresponding organ at risk physical doses were lowest using {sup 103}Pd in all circumstances. Conclusions: The results suggest that shorter implant durations may correlate with more favorable outcomes compared to 7 day implants when treating small or medium intraocular lesions. The data also indicate that implant duration may be safely reduced if the prescription physical dose is likewise diminished and that {sup 103}Pd offers a substantial radiobiological benefit over {sup 125}I and {sup 131}Cs irrespective of plaque position, implant duration, and tumor size.« less

Clickable, hydrophilic ligand for fac-[M(I)(CO)3](+) (M = Re/(99m)Tc) applied in an S-functionalized α-MSH peptide.

PubMed

Kasten, Benjamin B; Ma, Xiaowei; Liu, Hongguang; Hayes, Thomas R; Barnes, Charles L; Qi, Shibo; Cheng, Kai; Bottorff, Shalina C; Slocumb, Winston S; Wang, Jing; Cheng, Zhen; Benny, Paul D

2014-03-19

The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction was used to incorporate alkyne-functionalized dipicolylamine (DPA) ligands (1 and 3) for fac-[M(I)(CO)3](+) (M = Re/(99m)Tc) complexation into an α-melanocyte stimulating hormone (α-MSH) peptide analogue. A novel DPA ligand with carboxylate substitutions on the pyridyl rings (3) was designed to increase the hydrophilicity and to decrease in vivo hepatobiliary retention of fac-[(99m)Tc(I)(CO)3](+) complexes used in single photon emission computed tomography (SPECT) imaging studies with targeting biomolecules. The fac-[Re(I)(CO)3(3)] complex (4) was used for chemical characterization and X-ray crystal analysis prior to radiolabeling studies between 3 and fac-[(99m)Tc(I)(OH2)3(CO)3](+). The corresponding (99m)Tc complex (4a) was obtained in high radiochemical yields, was stable in vitro for 24 h during amino acid challenge and serum stability assays, and showed increased hydrophilicity by log P analysis compared to an analogous complex with nonfunctionalized pyridine rings (2a). An α-MSH peptide functionalized with an azide was labeled with fac-[M(I)(CO)3](+) using both click, then chelate (CuAAC reaction with 1 or 3 followed by metal complexation) and chelate, then click (metal complexation of 1 and 3 followed by CuAAC with the peptide) strategies to assess the effects of CuAAC conditions on fac-[M(I)(CO)3](+) complexation within a peptide framework. The peptides from the click, then chelate strategy had different HPLC tR's and in vitro stabilities compared to those from the chelate, then click strategy, suggesting nonspecific coordination of fac-[M(I)(CO)3](+) using this synthetic route. The fac-[M(I)(CO)3](+)-complexed peptides from the chelate, then click strategy showed >90% stability during in vitro challenge conditions for 6 h, demonstrated high affinity and specificity for the melanocortin 1 receptor (MC1R) in IC50 analyses, and led to moderately high uptake in B16F10 melanoma cells. Log P analysis of the (99m)Tc-labeled peptides confirmed the enhanced hydrophilicity of the peptide bearing the novel, carboxylate-functionalized DPA chelate (10a') compared to the peptide with the unmodified DPA chelate (9a'). In vivo biodistribution analysis of 9a' and 10a' showed moderate tumor uptake in a B16F10 melanoma xenograft mouse model with enhanced renal uptake and surprising intestinal uptake for 10a' compared to predominantly hepatic accumulation for 9a'. These results, coupled with the versatility of CuAAC, suggests this novel, hydrophilic chelate can be incorporated into numerous biomolecules containing azides for generating targeted fac-[M(I)(CO)3](+) complexes in future studies.

Synthesis, characterization of Ag(I), Pd(II) and Pt(II) complexes of a triazine-3-thione and their interactions with bovine serum albumin

NASA Astrophysics Data System (ADS)

Zhang, Xiuying; Li, Shuyan; Yang, Lin; Fan, Changqing

2007-11-01

Ag(I), Pd(II) and Pt(II) complexes of 5-methoxy-5,6-diphenyl-4,5-dihydro-2H-[1,2,4]triazine-3-thione (LH 2OCH 3) have been synthesized and characterized by elemental analysis, molar conductance, 1H NMR, IR spectra, UV spectra and thermal analysis (TG-DTA). The components of the three complexes are [Ag(C 15H 10N 3S)] 6, Pd(C 15H 10N 3S) 2 and Pt(C 15H 10N 3S) 2·C 3H 6O·2H 2O, respectively. All the complexes are nonelectrolyte and have high thermodynamic stability. The ligand may act as bidentate NS donor for Pd(II) and Pt(II) complexes, while it seems to be bidentate NS bridging via sulphur atom for Ag(I) complex. A planar quadrangular structure is proposed for Pd(II) and Pt(II) complexes and Ag(I) complex may be a hexanuclear cluster. Their interactions with bovine serum albumin (BSA) are investigated using steady state fluorescence technology. It is observed that all of them can quench the intrinsic fluorescence of BSA through static quenching procedure. The binding constants ( KA) at different temperatures, thermodynamic parameters enthalpy changes (Δ H) and entropy changes (Δ S) between BSA and the compounds are calculated. Based on the values of Δ H and Δ S, it is judged that the main acting force of PtL 2·C 3H 6O·2H 2O with BSA may be electrostatic interaction, and for the LH 2OCH 3, Ag 6L 6 and PdL 2, hydrophobic and electrostatic interactions may be involved in their binding processes.

Absolute activity quantitation from projections using an analytical approach: comparison with iterative methods in Tc-99m and I-123 brain SPECT

NASA Astrophysics Data System (ADS)

Fakhri, G. El; Kijewski, M. F.; Moore, S. C.

2001-06-01

Estimates of SPECT activity within certain deep brain structures could be useful for clinical tasks such as early prediction of Alzheimer's disease with Tc-99m or Parkinson's disease with I-123; however, such estimates are biased by poor spatial resolution and inaccurate scatter and attenuation corrections. We compared an analytical approach (AA) of more accurate quantitation to a slower iterative approach (IA). Monte Carlo simulated projections of 12 normal and 12 pathologic Tc-99m perfusion studies, as well as 12, normal and 12 pathologic I-123 neurotransmission studies, were generated using a digital brain phantom and corrected for scatter by a multispectral fitting procedure. The AA included attenuation correction by a modified Metz-Fan algorithm and activity estimation by a technique that incorporated Metz filtering to compensate for variable collimator response (VCR), IA-modeled attenuation, and VCR in the projector/backprojector of an ordered subsets-expectation maximization (OSEM) algorithm. Bias and standard deviation over the 12 normal and 12 pathologic patients were calculated with respect to the reference values in the corpus callosum, caudate nucleus, and putamen. The IA and AA yielded similar quantitation results in both Tc-99m and I-123 studies in all brain structures considered in both normal and pathologic patients. The bias with respect to the reference activity distributions was less than 7% for Tc-99m studies, but greater than 30% for I-123 studies, due to partial volume effect in the striata. Our results were validated using I-123 physical acquisitions of an anthropomorphic brain phantom. The IA yielded quantitation accuracy comparable to that obtained with IA, while requiring much less processing time. However, in most conditions, IA yielded lower noise for the same bias than did AA.

TU-F-CAMPUS-T-05: Dose Escalation to Biological Tumor Volumes of Prostate Cancer Patients Using Gold Nanoparticles

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

Jermoumi, M; Ngwa, W; Department of Radiation Oncology, Dana Farber Cancer Insitute, Brigham and Women’s Hospital, Harvard Medical, Boston, MA

2015-06-15

Purpose: Studies have shown that radiation boosting could help reduce prostate cancer (PCa) recurrence. Biological tumor volumes (BTV) are a high priority for such radiation boosting. The purpose of this study is to investigate the potential of radiation boosting of real patient BTVs using gold nanoparticles (GNP) released from gold-loaded brachytherapy spacers (GBS) during brachytherapy. Methods: The BTVs of 12 patients having prostate adenocarcinoma identified with positron emission tomography (PET) and CT scanner using C-11 labeled tracer [11C]acetate were investigated. The initial GNP concentration and time to achieve a dose enhancement effect (DEF) of 2 was simulated using the freelymore » downloadable software RAID APP. The investigations were carried out for low dose rate (LDR) brachytherapy sources (BTS) described in AAPM Task Group report 43: Cs-131, I-125, and Pd-103. In first case, we used 7 mg/g and 18 mg/g of GNP initial concentrations to estimate the time needed for released GNP to achieve a DEF of 2 for the different BTS, and compare with clinically relevant treatment times. In second case, we calculated the initial concentration of GNPs needed to achieve a DEF of 2 during the time the BTS would typically deliver 50%, 70% and 90% of the total dose. Results: For an initial concentration of 18 mg/g, when using Cs-131, and Pd-103, a DEF of 2 could only be achieved for BTV of 3.3 cm3 and 1 cm3 respectively. Meanwhile a DEF of 2 could be achieved for all 12 BTVs when using I-125. To achieve a DEF of 2 for all patients using Cs-131 and Pd-103, much higher initial concentrations would have to be used than have been typically employed in pre-clinical studies. Conclusion: The I-125 is the most viable BTS that can be employed with GBS to guide dose painting treatment planning for localized PCa.« less

Study of activation cross-sections of deuteron induced reactions on rhodium up to 40 MeV

NASA Astrophysics Data System (ADS)

Ditrói, F.; Tárkányi, F.; Takács, S.; Hermanne, A.; Yamazaki, H.; Baba, M.; Mohammadi, A.; Ignatyuk, A. V.

2011-09-01

In the frame of a systematic study of the activation cross-sections of deuteron induced nuclear reactions, excitation functions of the 103Rh(d,x) 100,101,103Pd, 100g,101m,101g,102m,102gRh and 103gRu reactions were determined up to 40 MeV. Cross-sections were measured with the activation method using a stacked foil irradiation technique. Excitation functions of the contributing reactions were calculated using the ALICE-IPPE, EMPIRE-II and TALYS codes. From the measured cross-section data integral production yields were calculated and compared with experimental integral yield data reported in the literature. From the measured cross-sections and previous data, activation curves were deduced to support thin layer activation (TLA) on rhodium and Rh containing alloys.

Differential effects of severe vs mild GBA mutations on Parkinson disease.

PubMed

Gan-Or, Ziv; Amshalom, Idan; Kilarski, Laura L; Bar-Shira, Anat; Gana-Weisz, Mali; Mirelman, Anat; Marder, Karen; Bressman, Susan; Giladi, Nir; Orr-Urtreger, Avi

2015-03-03

To better define the genotype-phenotype correlations between the type of GBA (glucosidase, beta, acid) mutation, severe or mild, and the risk and age at onset (AAO), and potential mechanism of Parkinson disease (PD). We analyzed 1,000 patients of Ashkenazi-Jewish descent with PD for 7 founder GBA mutations, and conducted a meta-analysis of risk and AAO according to GBA genotype (severe or mild mutation). The meta-analysis included 11,453 patients with PD and 14,565 controls from worldwide populations. The statistical analysis was done with and without continuity correction (constant or empirical), considering biases that could potentially affect the results. Among Ashkenazi-Jewish patients with PD, the odds ratios for PD were 2.2 and 10.3 for mild and severe GBA mutation carriers, respectively. The observed frequency of severe GBA mutation carriers among patients with PD was more than 4-fold than expected (4.4% vs 0.9%, respectively, p < 0.0001, Fisher exact test). In the different models of the meta-analysis, the odds ratios for PD ranged between 2.84 and 4.94 for mild GBA mutation carriers and 9.92 and 21.29 for severe GBA mutation carriers (p < 1 × 10(-6) for all analyses). Pooled analysis demonstrated AAO of 53.1 (±11.2) and 58.1 (±10.6) years for severe and mild GBA mutation carriers, respectively (p = 4.3 × 10(-5)). These data demonstrate that mild and severe heterozygous GBA mutations differentially affect the risk and the AAO of PD. Our results have important implications for genetic counseling and clinical follow-up. © 2015 American Academy of Neurology.

Prostate implant nomograms for the North American scientific {sup 103}Pd seed

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

Zheng, Jay J.; Stevens, Ritchie N

Palladium-103-({sup 103}Pd) seed has been increasingly used in prostate implantation as either definitive or boost therapy because of its shorter half-life and higher initial dose rate. Because a growing number of radiation oncologists prefer real-time implantation in the operating room, it will be helpful if the total activity of the seeds can be determined based on the gland size before the patient is taken to the operating room. Based on our clinic data, nomograms have therefore been developed for one of the widely used {sup 103}Pd seeds, the MED3633 seed, which is produced by North American Scientific, Inc. (NASI). Themore » total activities for implant volume ranging from 15 cc to 55 cc are provided for both seed 'monotherapy' and seed boost.« less

[Association of vitamin D receptor gene polymorphisms with mild cognitive impairment among elderly ethnic Uygurs].

PubMed

Zhou, Xiaohui; Zhu, Meisheng; Ma, Li; Miao, Haijun

2015-12-01

To assess the association of vitamin D receptor gene (VDR) Apa I, Bsm I genotypes and allele frequencies and mild cognitive impairment (MCI) among elderly ethnic Uygurs from Xinjiang, China. The polymorphisms of the VDR genotypes (Apa I and Bsm I) were analyzed by the SNaPshot method in 124 MCI patients and 124 controls. Factors which can increase the risk for MCI have included the A allele of the Apa I polymorphism [OR=1.62, 95%CI(1.13-2.31)] and the AA genotype [OR=3.49, 95% CI(1.57-7.74)], the T allele of the Bsm I polymorphism [OR=1.94, 95%CI(1.24-3.05)], higher triglyceride and systolic blood pressure levels. Polymorphisms of the VDR gene including the A allele and AA genotype of Apa I, and the T allele of Bsm I are probably associated with MCI among elderly ethnic Uygurs, and so are higher levels of triglyceride and systolic blood pressure.

KSC-08pd1170

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Ron Garan practices driving the M113 armored personnel carrier as part of emergency training. At center is the Battalion Chief George Hoggard, providing instruction. Behind Garan is Pilot Ken Ham. They and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1175

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Akihiko Hoshide drives the M113 armored personnel carrier as part of emergency training. Battalion Chief George Hoggard provides supervision. Behind them are Mission Specialist Ron Garan and Pilot Ken Ham. Hoshide and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1181

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Mike Fossum drives the M113 armored personnel carrier as part of emergency training. Behind him at left is Mission Specialist Greg Chamitoff. At center is Battalion Chief George Hoggard providing supervision. Fossum and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1539

NASA Image and Video Library

2008-05-31

CAPE CANAVERAL, Fla. -- At the Banana River viewing site, guests applaud the picture-perfect launch of space shuttle Discovery as it leaps from the clouds of smoke below on its STS-124 mission to the International Space Station. Launch was on time at 5:02 p.m. EDT. Discovery is making its 35th flight. The STS-124 mission is the 26th in the assembly of the space station. It is the second of three flights launching components to complete the Japan Aerospace Exploration Agency's Kibo laboratory. The shuttle crew will install Kibo's large Japanese Pressurized Module and its remote manipulator system, or RMS. The 14-day flight includes three spacewalks. Photo credit: NASA/Sam Fat

A Multimodal Imaging Protocol, (123)I/(99)Tc-Sestamibi, SPECT, and SPECT/CT, in Primary Hyperparathyroidism Adds Limited Benefit for Preoperative Localization.

PubMed

Lee, Grace S; McKenzie, Travis J; Mullan, Brian P; Farley, David R; Thompson, Geoffrey B; Richards, Melanie L

2016-03-01

Focused parathyroidectomy in primary hyperparathyroidism (1°HPT) is possible with accurate preoperative localization and intraoperative PTH monitoring (IOPTH). The added benefit of multimodal imaging techniques for operative success is unknown. Patients with 1°HPT, who underwent parathyroidectomy in 2012-2014 at a single institution, were retrospectively reviewed. Only the patients who underwent the standardized multimodal imaging workup consisting of (123)I/(99)Tc-sestamibi subtraction scintigraphy, SPECT, and SPECT/CT were assessed. Of 360 patients who were identified, a curative operation was performed in 96%, using pre-operative imaging and IOPTH. Imaging analysis showed that (123)I/(99)Tc-sestamibi had a sensitivity of 86% (95% CI 82-90%), positive predictive value (PPV) 93%, and accuracy 81%, based on correct lateralization. SPECT had a sensitivity of 77% (95% CI 72-82%), PPV 92% and accuracy 72%. SPECT/CT had a sensitivity of 75% (95% CI 70-80%), PPV of 94%, and accuracy 71%. There were 3 of 45 (7%) patients with negative sestamibi imaging that had an accurate SPECT and SPECT/CT. Of 312 patients (87%) with positive uptake on sestamibi (93% true positive, 7% false positive), concordant findings were present in 86% SPECT and 84% SPECT/CT. In cases where imaging modalities were discordant, but at least one method was true-positive, (123)I/(99)Tc-sestamibi was significantly better than both SPECT and SPECT/CT (p < 0.001). The inclusion of SPECT and SPECT/CT in 1°HPT imaging protocol increases patient cost up to 2.4-fold. (123)I/(99)Tc-sestamibi subtraction imaging is highly sensitive for preoperative localization in 1°HPT. SPECT and SPECT/CT are commonly concordant with (123)I/(99)Tc-sestamibi and rarely increase the sensitivity. Routine inclusion of multimodality imaging technique adds minimal clinical benefit but increases cost to patient in high-volume setting.

Effects of concurrent drug therapy on technetium /sup 99m/Tc gluceptate biodistribution

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

Hinkle, G.H.; Basmadjian, G.P.; Peek, C.

Drug interactions with /sup 99m/Tc gluceptate resulting in altered biodistribution were studied using chart review and animal tests. Charts of nine patients who had abnormal gallbladder uptake of technetium /sup 99m/Tc gluceptate during a two-year period were reviewed to obtain data such as concurrent drug therapy, primary diagnosis, and laboratory values. Adult New Zealand white rabbits were then used for testing the biodistribution of technetium /sup 99m/Tc gluceptate when administered concurrently with possibly interacting drugs identified in the chart review--penicillamine, penicillin G potassium, penicillin V potassium, acetaminophen, and trimethoprim-sulfamethoxazole. Chart review revealed no conclusive patterns of altered biodistribution associated withmore » other factors. The data did suggest the possibility that the five drugs listed above might cause increased hepatobiliary clearance of the radiopharmaceutical. Animal tests showed that i.v. penicillamine caused substantial distribution of radioactivity into the gallbladder and small bowel. Minimally increased gallbladder radioactivity occurred when oral acetaminophen and trimethoprim-sulfamethoxazole were administered concurrently. Oral and i.v. penicillins did not increase gallbladder activity. Penicillamine may cause substantial alteration of the biodistribution of technetium /sup 99m/Tc gluceptate.« less

A comparative study of PD-L1 immunohistochemical assays with four reliable antibodies in thymic carcinoma.

PubMed

Sakane, Tadashi; Murase, Takayuki; Okuda, Katsuhiro; Takino, Hisashi; Masaki, Ayako; Oda, Risa; Watanabe, Takuya; Kawano, Osamu; Haneda, Hiroshi; Moriyama, Satoru; Saito, Yushi; Yamada, Takeshi; Nakanishi, Ryoichi; Inagaki, Hiroshi

2018-01-23

Currently, four immunohistochemical assays are registered with the US Food and Drug Administration to detect the expression of PD-L1. We investigated the PD-L1 expression in thymic carcinomas using these four diagnostic assays. The cases of 53 patients were reviewed and their specimens were subjected to four PD-L1 assays with different antibodies (SP142, SP263, 22C3, and 28-8). The PD-L1 expression in tumor cells (TCs) and immune cells (ICs) was evaluated. In TCs, the four assays showed similar scores in each case. Histopathologically, high TC scores were observed in squamous cell carcinomas (SqCCs). Meanwhile, there were no significant relationships among the IC scores in the four assays. In SqCCs, the high expression of PD-L1 (defined as ≥50% TC score) in TCs tended to be associated with early stage cancer. The patients with high expression levels of PD-L1 tended to show longer overall survival in the 22C3 assays (p=0.0200). In thymic carcinomas, the staining pattern showed high concordance among the four assays when TCs - rather than ICs - were stained. High PD-L1 positivity in TCs, especially in SqCCs, indicated that PD-1/PD-L1 targeted therapy may be a promising therapeutic approach.

Investigation of magnetic order in SmTr2Zn20 (Tr = Fe, Co, Ru) and SmTr2Cd20 (Tr = Ni, Pd)

NASA Astrophysics Data System (ADS)

Yazici, Duygu; White, B. D.; Ho, P.-C.; Kanchanavatee, N.; Huang, K.; Dilley, N. R.; Maple, M. B.

2015-03-01

Single crystals of the cage compounds Sm Tr 2Zn20 (Tr = Fe, Co, Ru) and Sm Tr 2Cd20 (Tr = Ni, Pd) have been investigated by means of electrical resistivity, magnetization, and specific heat measurements. The compounds SmFe2Zn20, SmRu2Zn20,andSmNi2Cd20 exhibit ferromagnetic order with Curie temperatures of TC = 47.4 K, 7.6 K, and 7.5 K, respectively, whereas SmPd2Cd20 is an antiferromagnet with a Néel temperature of TN = 3.4 K. No evidence for magnetic order is observed in SmCo2Zn20 down to 110 mK. The Sommerfeld coefficients γ are found to be 57 mJ/mol-K2 for SmFe2Zn20, 79.5 mJ/mol-K2 for SmCo2Zn20, 258 mJ/mol-K2 for SmRu2Zn20, 165 mJ/mol-K2 for SmNi2Cd20, and 208 mJ/mol-K2 for SmPd2Cd20. Enhanced values of Sommerfeld coefficients γ and a quadratic temperature dependence of the electrical resistivity at low temperature for SmRu2Zn20andSmPd2Cd20 suggest an enhancement of the quasiparticle masses due to hybridization between localized 4 f and conduction electron states. Research at UCSD was supported by the U.S. DOE under Grant No. DE-FG02-04-ER46105 and the U.S. NSF under Award Grant No. DMR 1206553. Research at California State University, Fresno was supported by the U.S. NSF under Grant No. DMR 1104544.

High resolution CsI(Tl)/Si-PIN detector development for breast imaging

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

Patt, B.E.; Iwanczyk, J.S.; Tull, C.R.

High resolution multi-element (8x8) imaging arrays with collimators, size matched to discrete CsI(Tl) scintillator arrays and Si-PIN photodetector arrays (PDA`s) were developed as prototypes for larger arrays for breast imaging. Photodetector pixels were each 1.5 {times} 1.5 mm{sup 2} with 0.25 mm gaps. A 16-element quadrant of the detector was evaluated with a segmented CsI(Tl) scintillator array coupled to the silicon array. The scintillator thickness of 6 mm corresponds to >85% total gamma efficiency at 140 keV. Pixel energy resolution of <8% FWHM was obtained for Tc-99m. Electronic noise was 41 e{sup {minus}} RMS corresponding to a 3% FWHM contributionmore » to the 140 keV photopeak. Detection efficiency uniformity measured with a Tc-99m flood source was 4.3% for an {approximately}10% energy photopeak window. Spatial resolution was 1.53 mm FWHM and pitch was 1.75 mm as measured from the Co-57 (122 keV) line spread function. Signal to background was 34 and contrast was 0.94. The energy resolution and spatial characteristics of the new imaging detector exceed those of other scintillator based imaging detectors. A camera based on this technology will allow: (1) Improved Compton scatter rejection; (2) Detector positioning in close proximity to the breast to increase signal to noise; (3) Improved spatial resolution; and (4) Improved efficiency compared to high resolution collimated gamma cameras for the anticipated compressed breast geometries.« less

Isothiocyanate-Functionalized Bifunctional Chelates and fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) Complexes for Targeting uPAR in Prostate Cancer.

PubMed

Kasten, Benjamin B; Ma, Xiaowei; Cheng, Kai; Bu, Lihong; Slocumb, Winston S; Hayes, Thomas R; Trabue, Steven; Cheng, Zhen; Benny, Paul D

2016-01-20

Developing new strategies to rapidly incorporate the fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) core into biological targeting vectors in radiopharmaceuticals continues to expand as molecules become more complex and as efforts to minimize nonspecific binding increase. This work examines a novel isothiocyanate-functionalized bifunctional chelate based on 2,2'-dipicolylamine (DPA) specifically designed for complexing the fac-[M(I)(CO)3](+) core. Two strategies (postlabeling and prelabeling) were explored using the isothiocyanate-functionalized DPA to determine the effectiveness of assembly on the overall yield and purity of the complex with amine containing biomolecules. A model amino acid (lysine) examined (1) amine conjugation of isothiocyanate-functionalized DPA followed by complexation with fac-[M(I)(CO)3](+) (postlabeling) and (2) complexation of fac-[M(I)(CO)3](+) with isothiocyanate-functionalized DPA followed by amine conjugation (prelabeling). Conducted with stable Re and radioactive (99m)Tc analogs, both strategies formed the product in good to excellent yields under macroscopic and radiotracer concentrations. A synthetic peptide (AE105) which targets an emerging biomarker in CaP prognosis, urokinase-type plasminogen activator receptor (uPAR), was also explored using the isothiocyanate-functionalized DPA strategy. In vitro PC-3 (uPAR+) cell uptake assays with the (99m)Tc-labeled peptide (8a) showed 4.2 ± 0.5% uptake at 4 h. In a murine model bearing PC-3 tumor xenografts, in vivo biodistribution of 8a led to favorable tumor uptake (3.7 ± 0.7% ID/g) at 4 h p.i. with relatively low accumulation (<2% ID/g) in normal organs not associated with normal peptide excretion. These results illustrate the promise of the isothiocyanate-functionalized approach for labeling amine containing biological targeting vectors with fac-[M(I)(CO)3](+).

United States Army Combat Units of the War in the Republic of Vietnam: 1966-73. A Preliminary List

DTIC Science & Technology

1979-04-01

COMt , USASLPCCP # CHt CR8 -12 124 THANS UK 8 TRANS GP F1U .±18 125 ATC 210 CUT AVN EN BNH 23d 12b S.I UN - 25 INF CIV CCI. 22b 126 TRANS CGCL 4 TRANS... AGUST 63 UNIT APO UIC ADCON OPCON ARRIVAL COMo0060 EN DET MNT EC 96384 WBEK B4S B05 11 APR 66 5 0060 OD CO AMMO DS-GS .96491. .W61C, ",BOY BOY 19 NOV 66 5...TML COMT OP q6291 WFRT CJI CJT 01 OCT 66 5 0!ý-12 TC OtET TML S%/C JI 9)631ý? WFRIJ CKY CKY 01 NCT 66 051:? TC CO LT TRK 5T 9649? WFP7 FR6 FR6 PN

Genomic, Proteomic and Morphological Characterization of Two Novel Broad Host Lytic Bacteriophages ΦPD10.3 and ΦPD23.1 Infecting Pectinolytic Pectobacterium spp. and Dickeya spp.

PubMed Central

Czajkowski, Robert; Ozymko, Zofia; de Jager, Victor; Siwinska, Joanna; Smolarska, Anna; Ossowicki, Adam; Narajczyk, Magdalena; Lojkowska, Ewa

2015-01-01

Pectinolytic Pectobacterium spp. and Dickeya spp. are necrotrophic bacterial pathogens of many important crops, including potato, worldwide. This study reports on the isolation and characterization of broad host lytic bacteriophages able to infect the dominant Pectobacterium spp. and Dickeya spp. affecting potato in Europe viz. Pectobacterium carotovorum subsp. carotovorum (Pcc), P. wasabiae (Pwa) and Dickeya solani (Dso) with the objective to assess their potential as biological disease control agents. Two lytic bacteriophages infecting stains of Pcc, Pwa and Dso were isolated from potato samples collected from two potato fields in central Poland. The ΦPD10.3 and ΦPD23.1 phages have morphology similar to other members of the Myoviridae family and the Caudovirales order, with a head diameter of 85 and 86 nm and length of tails of 117 and 121 nm, respectively. They were characterized for optimal multiplicity of infection, the rate of adsorption to the Pcc, Pwa and Dso cells, the latent period and the burst size. The phages were genotypically characterized with RAPD-PCR and RFLP techniques. The structural proteomes of both phages were obtained by fractionation of phage proteins by SDS-PAGE. Phage protein identification was performed by liquid chromatography-mass spectrometry (LC-MS) analysis. Pulsed-field gel electrophoresis (PFGE), genome sequencing and comparative genome analysis were used to gain knowledge of the length, organization and function of the ΦPD10.3 and ΦPD23.1 genomes. The potential use of ΦPD10.3 and ΦPD23.1 phages for the biocontrol of Pectobacterium spp. and Dickeya spp. infections in potato is discussed. PMID:25803051

A general and high-yield galvanic displacement approach to Au-M (M = Au, Pd, and Pt) core-shell nanostructures with porous shells and enhanced electrocatalytic performances.

PubMed

Kuai, Long; Geng, Baoyou; Wang, Shaozhen; Sang, Yan

2012-07-23

In this work, we utilize the galvanic displacement synthesis and make it a general and efficient method for the preparation of Au-M (M = Au, Pd, and Pt) core-shell nanostructures with porous shells, which consist of multilayer nanoparticles. The method is generally applicable to the preparation of Au-Au, Au-Pd, and Au-Pt core-shell nanostructures with typical porous shells. Moreover, the Au-Au isomeric core-shell nanostructure is reported for the first time. The lower oxidation states of Au(I), Pd(II), and Pt(II) are supposed to contribute to the formation of porous core-shell nanostructures instead of yolk-shell nanostructures. The electrocatalytic ethanol oxidation and oxygen reduction reaction (ORR) performance of porous Au-Pd core-shell nanostructures are assessed as a typical example for the investigation of the advantages of the obtained core-shell nanostructures. As expected, the Au-Pd core-shell nanostructure indeed exhibits a significantly reduced overpotential (the peak potential is shifted in the positive direction by 44 mV and 32 mV), a much improved CO tolerance (I(f)/I(b) is 3.6 and 1.63 times higher), and an enhanced catalytic stability in comparison with Pd nanoparticles and Pt/C catalysts. Thus, porous Au-M (M = Au, Pd, and Pt) core-shell nanostructures may provide many opportunities in the fields of organic catalysis, direct alcohol fuel cells, surface-enhanced Raman scattering, and so forth. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design of Co/Pd multilayer system with antiferromagnetic-to-ferromagnetic phase transition

NASA Astrophysics Data System (ADS)

Thiele, Jan-Ulrich

2009-03-01

Among the known magnetic material systems there are only very few examples of materials that undergo a temperature dependent antiferromagnetic-to-ferromagnetic phase transition, and of these only the chemically ordered alloy FeRh exhibits this transition near room temperature [1, 2]. Here we present a perpendicular anisotropy multilayer structure that mimics FeRh. The basic idea is to use two stacks of Co/Pd multilayers with large perpendicular magnetic anisotropy and high Curie temperature, TC, separated by a layer providing antiferromagnetic coupling, and a CoNi/Pd multilayer with perpendicular anisotropy with a lower TC, interlayer, in the range of the desired AF-FM transition temperature, TAF-FM. At room temperature this system behaves as two antiferromagnetically coupled layers with a low perpendicular remanent magnetic moment. As the temperature is raised to approach TC, interlayer the magnetization of the interlayer is gradually reduced to zero, and consequently its coupling strength is reduced. Eventually, the effective coupling between the two high-KU, high-TC layers becomes dominated by their dipolar fields, resulting in a parallel alignment of their moments and a net remanent magnetic moment equal to the sum of the moments of the two high-TC layers [2]. [4pt] [1] J. S. Kouvel and C. C. Hartelius, J. Appl. Phys. 33 (1962) p1343 [0pt] [2] J.-U. Thiele, E. E. Fullerton, S. Maat, Appl. Phys. Lett. 82 (2003) p2859 [0pt] [3] J.-U. Thiele. T. Hauet. O. Hellwig, Appl. Phys. Lett. 92 (2008) 242502.

Induction of biliary cholangiocarcinoma cell apoptosis by 103Pd cholangial radioactive stent gamma-rays.

PubMed

He, Gui-jin; Sun, Dan-dan; Ji, Da-wei; Sui, Dong-ming; Yu, Fa-qiang; Gao, Qin-yi; Dai, Xian-wei; Gao, Hong; Jiang, Tao; Dai, Chao-liu

2008-06-05

In recent years, interventional tumor therapy, involving implantation of intra-cholangial metal stents through percutaneous trans-hepatic punctures, has provided a new method for treating cholangiocarcinoma. (103)Pd cholangial radioactive stents can concentrate high radioactive dosages into the malignant tumors and kill tumor cells effectively, in order to prevent re-stenosis of the lumen caused by a relapsed tumor. The aim of the present study was to investigate the efficacy of gamma-rays released by the (103)Pd biliary duct radioactive stent in treating cholangiocarcinoma via induction of biliary cholangiocarcinoma cell apoptosis. A group of biliary duct cancer cells was collectively treated with a dose of gamma-rays. Cells were then examined by the 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl terazolium-bromide (MTT) technique for determining the inhibition rate of the biliary duct cancer cells, as well as with other methods including electron microscopy, DNA agarose gel electrophoresis, and flow cytometry were applied for the evaluation of their morphological and biochemical characteristics. The growth curve and the growth inhibition rate of the cells were determined, and the changes in the ultrastructure of the cholangiocarcinoma cells and the DNA electrophoresis bands were examined under a UV-lamp. The gamma-ray released by (103)Pd inhibited cholangiocarcinoma cell growth, as demonstrated when the growth rate of the cells was stunned by a gamma-ray with a dosage larger than 197.321 MBq. Typical features of cholangiocarcinoma cell apoptosis were observed in the 197.321 MBq dosage group, while cell necrosis was observed when irradiated by a dosage above 245.865 MBq. DNA agarose gel electrophoresis results were different between the 197.321 MBq irradiation dosage group, the 245.865 MBq irradiation dosage group, and the control group. (103)Pd radioactive stents which provide a radioactive dosage of 197.321 MBq are effective in the treatment of cholangiocarcinoma; (103)Pd radioactive stents should be useful for the clinical treatment of cholangiocarcinoma.

Evaluation of a Novel Tc-99m Labelled Vitamin B12 Derivative for Targeting Escherichia coli and Staphylococcus aureus In Vitro and in an Experimental Foreign-Body Infection Model.

PubMed

Baldoni, Daniela; Waibel, Robert; Bläuenstein, Peter; Galli, Filippo; Iodice, Violetta; Signore, Alberto; Schibli, Roger; Trampuz, Andrej

2015-12-01

Vitamin B12 (cyanocobalamin, Cbl) is accumulated by rapidly replicating prokaryotic and eukaryotic cells. We investigated the potential of a Tc-99m labelled Cbl derivative ([(99m)Tc]PAMA(4)-Cbl) for targeting infections caused by Escherichia coli and Staphylococcus aureus. In vitro binding assays were followed by biodistribution studies in a mouse model of foreign body infection. E. coli (ATCC 25922) and S. aureus (ATCC 43335) were used as test strains. [(57)Co]Cbl, [(67)Ga]citrate and [(99m)Tc]DTPA served as reference compounds. The in vitro competitive binding of [(57)Co]Cbl or [(99m)Tc]PAMA(4)-Cbl, and unlabeled Cbl, to viable or killed bacteria, was evaluated at 37 and 4 °C. A cage mouse model of infection was used for biodistribution of intravenous [(57)Co]Cbl and [(99m)Tc]PAMA(4)-Cbl in cage and dissected tissues of infected and non-infected mice. Maximum binding (mean ± SD) of [(57)Co]Cbl to viable E. coli was 81.7 ± 2.6 % and to S. aureus 34.0 ± 6.7 %, at 37 °C; no binding occurred to heat-killed bacteria. Binding to both test strains was displaced by 100- to 1000-fold excess of unlabeled Cbl. The in vitro binding of [(99m)Tc]PAMA(4)-Cbl was 100-fold and 3-fold lower than the one of [(57)Co]Cbl for E. coli and S. aureus, respectively. In vivo, [(99m)Tc]PAMA(4)-Cbl showed peak percentage of injected dose (% ID) values between 1.33 and 2.3, at 30 min post-injection (p.i.). Significantly higher retention occurred in cage fluids infected with S. aureus at 4 h and with E. coli at 8 h p.i. than in non-infected animals. Accumulation into infected cages was also higher than the one of [(99m)Tc]DTPA, which showed similar biodistribution in infected and sterile mice. [(57)Co]Cbl gradually accumulated in cages with peaks % ID between 3.58 and 4.83 % achieved from 24 to 48 h. Discrimination for infection occurred only in E. coli-infected mice, at 72 h p.i. [(67)Ga]citrate, which showed a gradual accumulation into cage fluids during 12 h, was discriminative for infection from 48 to 72 h p.i. (P < 0.05). Cbl displayed rapid and specific in vitro binding to test strains. [(99m)Tc]PAMA(4)-Cbl was rapidly cleared from most tissues and discriminated between sterile and infected cages, being a promising candidate for imaging infections in humans.

Computations and Experiments of Shallow Depth Explosion Plumes

DTIC Science & Technology

1996-08-01

cast) 1.60 1.29 Pentolite 1.67 1.31 COMP C-4 1.6 1.34 PBXN -103 1.87 1.23 HBX-1 1.72 1.23 NSWCDD/TR-94 156 data presented in Reference 19 for TNT, the...BASED ON PERIOD MEASUREMENTS I As in Table 3-5, the estimations for Jo appear to be larger for smaller values of C (with the excep- tion of the PBXN ...the bubbles were not photographed for the HBX-1 or PBXN -103 shotsI listed in Table 3-6. The explosive bubble parameters used in the next chapter are

Diagnosis of Pediatric Hyperthyroidism: Technetium 99 Uptake Versus Thyroid Stimulating Immunoglobulins

PubMed Central

Misra, Madhusmita; Levitsky, Lynne L.

2015-01-01

Background: Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with 123I or 99Tc (99mTc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with 99mTc uptake for diagnosis of pediatric hyperthyroidism. Methods: We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and 99mTc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. 99mTc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Results: Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI–. Elevated TSI correlated with Tc+ (p=0.01) with a degree of agreement (kappa) of 0.69. Conclusion: 99mTc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of 99mTc (two and a half times as much as TSI), it is reasonable to reserve 99mTc uptake assessment for hyperthyroidism of unclear etiology and negative TSI. PMID:25257665

Diagnosis of pediatric hyperthyroidism: technetium 99 uptake versus thyroid stimulating immunoglobulins.

PubMed

Baskaran, Charumathi; Misra, Madhusmita; Levitsky, Lynne L

2015-01-01

Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with (123)I or (99)Tc ((99m)Tc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with (99m)Tc uptake for diagnosis of pediatric hyperthyroidism. We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and (99m)Tc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. (99m)Tc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI-. Elevated TSI correlated with Tc+ (p=0.01) with a degree of agreement (kappa) of 0.69. (99m)Tc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of (99m)Tc (two and a half times as much as TSI), it is reasonable to reserve (99m)Tc uptake assessment for hyperthyroidism of unclear etiology and negative TSI.

The Purity of Radioiodide-I131 Assessed by in Vivo and in Vitro Methods

PubMed Central

Fawcett, D. M.; Olde, G. L.; McLeod, L. E.

1962-01-01

Between 41 and 94% of the radioactivity of 24 preparations of I131 supplied without cysteine preservative was non-iodide on chromatographic analysis. Extraneous radio-activity was essentially absent from I131 supplied with cysteine. It was converted to iodide-I131 by 10-3 M cysteine or iodide but not by incubation at pH 2. The average thyroid uptake of I131 containing extraneous radioactivity was significantly lower than the uptake of I131 free from non-iodide impurity in 16 human subjects measured under controlled conditions and in a random group of 669 patients. Incubation of samples of I131 containing non-iodide radioactivity with tyrosine and cupric chloride resulted in the non-enzymatic formation of monoiodotyrosine-I131 either in the presence or absence of thyroid homogenate. Enzymatic formation of monoiodotyrosine-I131 by thyroid homogenates could be demonstrated only when I131 free from extraneous activity was used. ImagesFig. 1Fig. 2 PMID:13891874

Monte Carlo calculated doses to treatment volumes and organs at risk for permanent implant lung brachytherapy

NASA Astrophysics Data System (ADS)

Sutherland, J. G. H.; Furutani, K. M.; Thomson, R. M.

2013-10-01

Iodine-125 (125I) and Caesium-131 (131Cs) brachytherapy have been used with sublobar resection to treat stage I non-small cell lung cancer and other radionuclides, 169Yb and 103Pd, are considered for these treatments. This work investigates the dosimetry of permanent implant lung brachytherapy for a range of source energies and various implant sites in the lung. Monte Carlo calculated doses are calculated in a patient CT-derived computational phantom using the EGsnrc user-code BrachyDose. Calculations are performed for 103Pd, 125I, 131Cs seeds and 50 and 100 keV point sources for 17 implant positions. Doses to treatment volumes, ipsilateral lung, aorta, and heart are determined and compared to those determined using the TG-43 approach. Considerable variation with source energy and differences between model-based and TG-43 doses are found for both treatment volumes and organs. Doses to the heart and aorta generally increase with increasing source energy. TG-43 underestimates the dose to the heart and aorta for all implants except those nearest to these organs where the dose is overestimated. Results suggest that model-based dose calculations are crucial for selecting prescription doses, comparing clinical endpoints, and studying radiobiological effects for permanent implant lung brachytherapy.

Phase Structure and Site Preference Behavior of Ternary Alloying Additions to PdTi and PtTi Shape-Memory Alloys

NASA Technical Reports Server (NTRS)

Bozzolo, Guillermo; Mosca, Hugo O.; Noebe, Ronald D.

2006-01-01

The phasc structure and concentration dependence of the lattice parameter and energy of formation of ternary Pd-'I-X and Pt-Ti-X alloys for a large number of ternary alloying additions X (X = Na, Mg, Al, Si, Sc. V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Nb, Mo, Tc, Ru, Rh, Ag, Cd, Hf, Ta, W, Re, Os, Ir) are investigated with an atomistic modeling approach. In addition, a detailed description of the site preference behavior of such additions showing that the elements can be grouped according to their absolute preference for a specific site, regardless of concentration, or preference for available sites in the deficient sublattice is provided.

Brain perfusion alterations in depressed patients with Parkinson's disease.

PubMed

Kim, Young-Do; Jeong, Hyeonseok S; Song, In-Uk; Chung, Yong-An; Namgung, Eun; Kim, Yong-Duk

2016-12-01

Although Parkinson's disease (PD) is frequently accompanied by depression, brain perfusion deficits in PD with depression remain unclear. This study aimed to assess alterations in regional cerebral blood flow (rCBF) in depressed PD patients using 99m Tc hexamethyl-propylene-amine-oxime single-photon emission computed tomography (SPECT). Among 78 patients with PD, 35 patients were classified into the depressed PD group, while the rest (43 patients) was assigned to the nondepressed PD group based on the scores of the Geriatric Depressive Scale (GDS). All participants underwent brain SPECT imaging. The voxel-wise whole-brain analysis and region-of-interest (ROI) analysis of the limbic areas were conducted to compare rCBF between the depressed and nondepressed PD groups. The depressed PD patients demonstrated higher GDS scores than nondepressed patients, whereas between-group differences in the PD severity and cognitive function were not significant. Perfusion in the left cuneus was increased, while that in the right superior temporal gyrus and right medial orbitofrontal cortex was reduced in the depressed PD patients as compared with nondepressed PD patients. In addition, the ROI analysis demonstrated rCBF decreases in the amygdala, anterior cingulate cortex, hippocampus, and parahippocampal gyrus in the depressed PD group. A positive correlation was found between the GDS scores and rCBF in the left cuneus cluster in the depressed PD patients. This study identified the regional pattern of brain perfusion that distinguished depressed from nondepressed PD patients. Hyperperfusion in the occipital areas and hypoperfusion in the fronto-temporo-limbic regions may be potential imaging biomarkers for depression in PD.

Effect of nitrate on uptake of pertechnetate by tomato plants

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

Krijger, G.C.; Kolloeffel, C.; Wolterbeek, H.T.

Nitrate has been shown to affect the acquisition of the nuclear waste product technetium (Tc) by plants. The mechanism responsible for this phenomenon is unknown. The uptake of [{sup 99m}Tc]TcO{sub 4}{sup {minus}},[{sup 35}S] SO{sub 4}{sup 2{minus}} and H{sub 2}[{sup 32P}]PO{sub 4}{sup {minus}} was studied in tomato plants (Lycopersicon esculentum Mill., cv. Tiny Tim) with different growth rates due to culture at 0.5, 4.0, or 30 mM NO{sub 3}{sup {minus}}. In experiments lasting 24 h, net TcO{sub 4}{sup {minus}} uptake decreased at higher NO{sub 3}{sup {minus}} supplies. The inhibitory effect of NO{sub 3}{sup {minus}} on TcO{sub 4}{sup {minus}} uptake also wasmore » shown in TcO{sub 4}{sup {minus}} influx experiments (K{sub i} = 3.3 mM), although about 30% of the TcO{sub 4}{sup {minus}} influx is suggested to be insensitive to NO{sub 3}{sup {minus}}. In contrast, H{sub 2}PO{sub 4}{sup {minus}} (30 mM) did not inhibit TcO{sub 4}{sup {minus}} influx, whereas SO{sub 4}{sup 2{minus}} (30 mM) tended to increase TcO{sub 4}{sup {minus}} influx, probably due to the ionic strength of the uptake solution. Significant effects of the NO{sub 3}{sup {minus}} supply on Tc efflux were not found. Overall, this leads to the conclusion that TcO{sub 4}{sup {minus}} and NO{sub 3}{sup {minus}} share at least one transporter.« less

Holey nickel-cobalt layered double hydroxide thin sheets with ultrahigh areal capacitance

NASA Astrophysics Data System (ADS)

Zhi, Lei; Zhang, Wenliang; Dang, Liqin; Sun, Jie; Shi, Feng; Xu, Hua; Liu, Zonghuai; Lei, Zhibin

2018-05-01

Strong coupling of electroactive components on conductive carbonaceous matrix to fabricate flexible hybrid electrodes represents a promising approach towards high performance supercapacitors. This work reports the fabrication of holey nickel cobalt layered double hydroxide (NiCo-LDH) nanosheets that are vertically grown on the cotton cloth-derived activated textile carbon (aTC). The abundant nanoholes on the thin-sheet NiCo-LDH not only enhance the electrode efficiency for efficient Faradaic redox reactions but also facilitate access of electrolyte to the electrode surface, thus giving rise to 70% capacitance arising from their outer surface. As a result, the aTC-NiCo hybrid electrode is capable of simultaneously achieving extremely high areal capacitance (6.37 F cm-2), mass capacitance (525 F g-1) and volumetric capacitance (249 F cm-3) at a practical level of mass loading (6.72 mg cm-2). Moreover, a solid-state asymmetric capacitor built with aTC-NiCo as positive electrode and active carbon-coated on aTC as negative electrode can deliver a volumetric energy density of 7.4 mWh cm-3 at a power density of 103 mW cm-3, while preserving a superior power performance, satisfying cycling stability and good mechanical flexibility.

Chemogenetic stimulation of striatal projection neurons modulates responses to Parkinson’s disease therapy

PubMed Central

Alcacer, Cristina; Andreoli, Laura; Sebastianutto, Irene; Jakobsson, Johan; Fieblinger, Tim; Cenci, Maria Angela

2017-01-01

Parkinson’s disease (PD) patients experience loss of normal motor function (hypokinesia), but can develop uncontrollable movements known as dyskinesia upon treatment with L-DOPA. Poverty or excess of movement in PD has been attributed to overactivity of striatal projection neurons forming either the indirect (iSPNs) or the direct (dSPNs) pathway, respectively. Here, we investigated the two pathways’ contribution to different motor features using SPN type–specific chemogenetic stimulation in rodent models of PD (PD mice) and L-DOPA–induced dyskinesia (LID mice). Using the activatory Gq-coupled human M3 muscarinic receptor (hM3Dq), we found that chemogenetic stimulation of dSPNs mimicked, while stimulation of iSPNs abolished the therapeutic action of L-DOPA in PD mice. In LID mice, hM3Dq stimulation of dSPNs exacerbated dyskinetic responses to L-DOPA, while stimulation of iSPNs inhibited these responses. In the absence of L-DOPA, only chemogenetic stimulation of dSPNs mediated through the Gs-coupled modified rat muscarinic M3 receptor (rM3Ds) induced appreciable dyskinesia in PD mice. Combining D2 receptor agonist treatment with rM3Ds-dSPN stimulation reproduced all symptoms of LID. These results demonstrate that dSPNs and iSPNs oppositely modulate both therapeutic and dyskinetic responses to dopamine replacement therapy in PD. We also show that chemogenetic stimulation of different signaling pathways in dSPNs leads to markedly different motor outcomes. Our findings have important implications for the design of effective antiparkinsonian and antidyskinetic drug therapies. PMID:28112685

Critical Temperature of Randomly Diluted Two-Dimensional Heisenberg Ferromagnet, K2CuxZn(1-x)F4

NASA Astrophysics Data System (ADS)

Okuda, Yuichi; Tohi, Yasuto; Yamada, Isao; Haseda, Taiichiro

1980-09-01

The susceptibility of randomly diluted two-dimensional Heisenberg-like ferromagnet K2CuxZn(1-x)F4 was measured down to 50 mK, using the 3He-4He dilution refrigerator and a SQUID magnetometer. The ferromagnetic critical temperature Tc(x) was obtained for x{=}0.98, 0.94, 0.85, 0.82, 0.68, 0.60, 0.54, 0.50 and 0.42. The value of [1/Tc(1)][(d/dx)Tc(x)]x=1 was approximately 3.0. The critical temperature versus x curve exhibits a noticeable tail near the critical concentration, which may stem from the second nearest-neighbor interaction. The critical concentration xc, below which concentration there is no long range order down to T{=}0 K, was estimated to be 0.45˜0.50. The susceptibility of sample with x{=}0.42 behaves as if it obeys the Curie law down to 50 mK.

Addressing the third gamma problem in PET

NASA Astrophysics Data System (ADS)

Schueller, M. J.; Mulnix, T. L.; Christian, B. T.; Jensen, M.; Holm, S.; Oakes, T. R.; Roberts, A. D.; Dick, D. W.; Martin, C. C.; Nickles, R. J.

2003-02-01

PET brings the promise of quantitative imaging of the in-vivo distribution of any positron emitting nuclide, a list with hundreds of candidates. All but a few of these, the "pure positron" emitters, have isotropic coincident gamma rays that give rise to misrepresented events in the sinogram and in the resulting reconstructed image. Of particular interest are /sup 10/C, /sup 14/O, /sup 38/K, /sup 52m/Mn, /sup 60/Cu, /sup 61/Cu, /sup 94m/Tc, and /sup 124/I, each having high-energy gammas that are Compton-scattered down into the 511 keV window. The problems arising from the "third gamma," and its accommodation by standard scatter correction algorithms, were studied empirically, employing three scanner models (CTI 933/04, CTI HR+ and GE Advance), imaging three phantoms (line source, NEMA scatter and contrast/detail), with /sup 18/F or /sup 38/K and /sup 72/As mimicking /sup 14/O and /sup 10/C, respectively, in 2-D and 3-D modes. Five findings emerge directly from the image analysis. The third gamma: 1) does, obviously, tax the single event rate of the PET scanners, particularly in the absence of septa, from activity outside of the axial field of view; 2) does, therefore, tax the random rate, which is second order in singles, although the gamma is a prompt coincidence partner; 3) does enter the sinogram as an additional flat background, like randoms, but unlike scatter; 4) is not seriously misrepresented by the scatter algorithm which fits the correction to the wings of the sinogram; and 5) does introduce additional statistical noise from the subsequent subtraction, but does not seriously compromise the detectability of lesions as seen in the contrast/detail phantom. As a safeguard against the loss of accuracy in image quantitation, fiducial sources of known activity are included in the field of view alongside of the subject. With this precaution, a much wider selection of imaging agents can enjoy the advantages of positron emission tomography.

Quaternary borocarbides: New class of intermetallic superconductors

NASA Technical Reports Server (NTRS)

Nagarajan, R.; Gupta, L. C.; Dhar, S. K.; Mazumdar, Chandan; Hossain, Zakir; Godart, C.; Levy-Clement, C.; Padalia, B. D.; Vijayaraghavan, R.

1995-01-01

Our recent discovery of superconductivity (SC) in the four-element multiphase Y-Ni-B-C system at an elevated temperature (TC approximately 12 K) has opened up great possibilities of identifying new superconducting materials and generating new physics. Superconductivity with Tc (greater than 20 K) higher than that known so far in bulk intermetallics has been observed in multiphase Y-Pd-B-C and Th-Pd-B-C systems and a family of single phase materials RENi2B2C (RE= Y, rare earth) have been found. Our investigations show YNi2B2C to be a strong coupling hard type-II SC. HC2(T) exhibits an unconventional temperature dependence. Specific heat and magnetization studies reveal coexistence of SC and magnetism in RNi2B2C (R = Ho, Er, Tm) with magnetic ordering temperatures (Tc approximately 8 K, 10.5 K, 11 K and Tm approximately 5 K, approximately 7K, approximately 4 K respectively) that are remarkably higher than those in known magnetic superconductors . Mu-SR studies suggest the possibility of Ni atoms carrying a moment in TmNi2B2C. Resistivity results suggests a double re-entrant transition (SC-normal-SC) in HoNi2B2C. RENi2B2C (RE = Ce, Nd, Gd) do not show SC down to 4.2 K. The Nd- and Gd-compounds order magnetically at approximately 4.5 K and approximately 19.5 K, respectively. Two SC transitions are observed in Y-Pd-B-C (Tc approximately 22 K, approximately 10 K) and in Th-Pd-B-C (Tc approximately 20 K, approximately 14 K) systems, which indicate that there are at least two structures which support SC in these borocarbides. In our multiphase ThNi2B2C we observe SC at approximately 6 K. No SC was seen in multiphase UNi2B2C, UPd2B2C, UOs2Ge2C and UPd5B3C(0.35) down to 4.2 K. Tc in YNi2B2C is depressed by substitutions (Gd, Th and U at Y-sites and Fe, Co at Ni-sites).

Quantitative studies of bone using (18)F-fluoride and (99m)Tc-methylene diphosphonate: evaluation of renal and whole-blood kinetics.

PubMed

Park-Holohan, S J; Blake, G M; Fogelman, I

2001-09-01

We report a study of the renal and whole-blood kinetics of (18)F-fluoride and (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) and their effect on the evaluation of the skeletal kinetics of the two bone tracers. Data were obtained during an investigation of postmenopausal women taking hormone replacement therapy who were compared with untreated, age-matched controls. After intravenous injection of 18F-fluoride (1 MBq), (99m)Tc-MDP (1 MBq), (51)Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) (3 MBq) and (125)I-human serum albumin ((125)I-HSA) (0.25 MBq), multiple blood samples and urine collections were taken between 0 and 4 h after injection. (51)Cr-EDTA data were used to evaluate the glomerular filtration rate (GFR) and the completeness of each timed urine collection. (125)I-HSA data were used to evaluate the plasma volume and the red cell uptake of the other three tracers. At 4 h, the cumulative urine excretions (and standard deviations, SDs) were: (99m)Tc-MDP, 58.2% (4.8%); (18)F-fluoride, 36.1% (5.7%); (51)Cr-EDTA, 81.5% (4.5%). Plots of the renal clearance of (18)F-fluoride against urine volume showed that urine flow rates greater than 5 ml.min-1 were necessary to ensure a constant renal clearance of (18)F and hence stable conditions for the evaluation of bone tracer kinetics. In contrast, a low urine flow rate had no effect on the renal kinetics of (99m)Tc-MDP. For MDP, the evaluation of skeletal kinetics requires data on protein binding so that calculations can be performed for free MDP. In the present study, protein binding of MDP was evaluated from the ratio of total (99m)Tc-MDP renal clearance to GFR based on the principle that free (99m)Tc-MDP is a GFR tracer. Between 0 and 4 h after injection, the fractional protein binding of MDP increased linearly with time, changing from 21+/-5% immediately after injection to 58+/-5% at 4 h. Although red cell uptake of (99m)Tc-MDP was negligible, for (18)F-fluoride around 30% of circulating tracer was transported in red cells. In view of the data showing the rapid transport of (18)F-fluoride across the red cell membrane, bone kinetic data for (18)F are more accurately reported as whole-blood clearance rather than plasma clearance.

Application of a Physiologically Based Pharmacokinetic Model to Predict OATP1B1-Related Variability in Pharmacodynamics of Rosuvastatin

PubMed Central

Rose, R H; Neuhoff, S; Abduljalil, K; Chetty, M; Rostami-Hodjegan, A; Jamei, M

2014-01-01

Typically, pharmacokinetic–pharmacodynamic (PK/PD) models use plasma concentration as the input that drives the PD model. However, interindividual variability in uptake transporter activity can lead to variable drug concentrations in plasma without discernible impact on the effect site organ concentration. A physiologically based PK/PD model for rosuvastatin was developed that linked the predicted liver concentration to the PD response model. The model was then applied to predict the effect of genotype-dependent uptake by the organic anion-transporting polypeptide 1B1 (OATP1B1) transporter on the pharmacological response. The area under the plasma concentration–time curve (AUC0–∞) was increased by 63 and 111% for the c.521TC and c.521CC genotypes vs. the c.521TT genotype, while the PD response remained relatively unchanged (3.1 and 5.8% reduction). Using local concentration at the effect site to drive the PD response enabled us to explain the observed disconnect between the effect of the OATP1B1 c521T>C polymorphism on rosuvastatin plasma concentration and the cholesterol synthesis response. PMID:25006781

Towards Solving the Conundrum of Fast-Spread Ocean Crust Formation: Insights from Textural Analysis of Gabbroic Rocks from Pito Deep and Hess Deep, East Pacific Rise

NASA Astrophysics Data System (ADS)

Brown, T. C.; Cheadle, M. J.; John, B. E.; Coogan, L. A.; Gee, J. S.; Karson, J. A.; Meyer, R.; Ceuleneer, G.; Swapp, S.

2014-12-01

Few examples of in situ fast-spread lower ocean crust exist for sampling. Here we present detailed textural analyses of two sample sets that formed at the East Pacific Rise, collected from tectonic windows at Pito (PD) and Hess (HD) deeps. PD samples (collected by ROV) span the upper ~900 m of lower crust. HD samples (collected by seafloor drilling during IODP Exp. 345) come from >1500 m below the sheeted dike gabbro transition (mbsd). PD gabbroic rock textures are consistent with a gabbro glacier flow model generating the uppermost plutonic crust. Shallow samples (41-72 mbsd) likely formed at the distal edge of the magma lens, analogous to similar rocks from Oman. These gabbros are relatively evolved (cpx Mg#75-77, An53-61 and 1-4% Fe-Ti oxides), and have elongate plagioclase grains (aspect ratios up to 1:2:10) exhibiting a strong shape preferred orientation (SPO) with <40% of grains showing dislocation creep textures. Deeper samples (177-876 mbsd) likely began crystallizing in the magma lens then subsided and 'flowed' through the underlying mush zone. These gabbros are more primitive below 386 mbsd (Fo83-88, cpx Mg# 85-89 and An70-82), and plagioclase grains have more equilibrated morphologies (aspect ratios < 1:2:6) that define ~vertical SPOs which increase in strength with depth. Plagioclase exhibits magmatic crystal-lattice preferred orientations (CPOs) which are also vertical. Significantly, the proportion of grains showing dislocation creep textures increases with depth, and plagioclase grain size distributions show a smaller range of sizes at depth; observations that perhaps reflect the effect of increasing strain with depth. IODP Hole U1415I at HD recovered gabbros and troctolitic gabbros from the mid lower crust that show distinctive cm-dm scale modal layering. Strong plagioclase SPOs parallel layering and magmatic CPOs vary dramatically in strength over just 4.5 m of core. Plagioclase grains are relatively equant (aspect ratios < 1:2:4), wrap around large cpx oikocrysts, and exhibit fewer dislocation creep textures than the PD gabbros. These observations perhaps suggest primary crystal accumulation rather than bulk strain/flow. The similar mineralogy and textures of these samples to those from the Rum layered intrusion suggest HD U1415I gabbros may have formed by mid-crust sill injection.

KSC-08pd1183

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- After completing M113 driving practice, the STS-124 crew stands in front of the armored personnel carrier for a photo. From left are Commander Mark Kelly, Mission Specialists Mike Fossum, Karen Nyberg and Ron Garan, Pilot Ken Ham, and Mission Specialists Akihiko Hoshide and Greg Chamitoff. They are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1168

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 crew members get instructions inside an M113 armored personnel carrier about emergency procedures. Clockwise from left are Mission Specialists Greg Chamitoff and Akihiko Hoshide, Commander Mark Kelly, Mission Specialist Ron Garan, instructor Battalion Chief George Hoggard, Pilot Ken Ham and Mission Specialists Karen Nyberg and Mike Fossum. They are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1177

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- With Launch Pad 39B in the background, STS-124 Pilot Ken Ham drives the M113 armored personnel carrier as part of emergency training. Behind him at right is Mission Specialist Karen Nyberg. At center is Battalion Chief George Hoggard providing supervision. Ham and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

Achieving BLISS: Challenges for Building Fast, Ultra-Sensitive Transition-Edge Sensors

NASA Technical Reports Server (NTRS)

Beyer, Andrew D.; Runyan, M. C.; Kenyon, M.; Echternach, P. M .; Chui, T.; Bumble, B.; Bradford, C. M.; Holmes, W. A.; Bock, J. J.

2012-01-01

Topics: 1.Motivation and Intro to TESs. 2. BLISS Specifications-tolerance to dark power. 3.Measuring stray (dark) power-Tc (alpha) and G measurements. a) Overview two methods: JTD vs. TES. b) TES arrays: measurement and complications for Pd, Tc, and alpha. 4. Results: Pd compare, NEP, tau, 1/f issues. LIRGs and ULIRGs: Excellent example of distinct optical/UV and IR luminosity. Interaction long known, but huge luminosity is not predicted based on optical studies. (greater than 90% of the energy is emitted at in the far-IR). Large luminosity has both starburst and accretion components.

eIF1 Loop 2 interactions with Met-tRNAi control the accuracy of start codon selection by the scanning preinitiation complex.

PubMed

Thakur, Anil; Hinnebusch, Alan G

2018-05-01

The eukaryotic 43S preinitiation complex (PIC), bearing initiator methionyl transfer RNA (Met-tRNA i ) in a ternary complex (TC) with eukaryotic initiation factor 2 (eIF2)-GTP, scans the mRNA leader for an AUG codon in favorable context. AUG recognition evokes rearrangement from an open PIC conformation with TC in a "P OUT " state to a closed conformation with TC more tightly bound in a "P IN " state. eIF1 binds to the 40S subunit and exerts a dual role of enhancing TC binding to the open PIC conformation while antagonizing the P IN state, necessitating eIF1 dissociation for start codon selection. Structures of reconstituted PICs reveal juxtaposition of eIF1 Loop 2 with the Met-tRNA i D loop in the P IN state and predict a distortion of Loop 2 from its conformation in the open complex to avoid a clash with Met-tRNA i We show that Ala substitutions in Loop 2 increase initiation at both near-cognate UUG codons and AUG codons in poor context. Consistently, the D71A-M74A double substitution stabilizes TC binding to 48S PICs reconstituted with mRNA harboring a UUG start codon, without affecting eIF1 affinity for 40S subunits. Relatively stronger effects were conferred by arginine substitutions; and no Loop 2 substitutions perturbed the rate of TC loading on scanning 40S subunits in vivo. Thus, Loop 2-D loop interactions specifically impede Met-tRNA i accommodation in the P IN state without influencing the P OUT mode of TC binding; and Arg substitutions convert the Loop 2-tRNA i clash to an electrostatic attraction that stabilizes P IN and enhances selection of poor start codons in vivo.

Hyperthermic fatigue precedes a rapid reduction in serum sodium in an ironman triathlete: a case report.

PubMed

Laursen, Paul B; Watson, Greig; Abbiss, Chris R; Wall, Bradley A; Nosaka, Kazunori

2009-12-01

To monitor the hydration, core temperature, and speed (pace) of a triathlete performing an Ironman triathlon. A 35-year-old experienced male triathlete participated in the Western Australian Ironman triathlon on December 1, 2006. The participant was monitored for blood Na(+) concentration before the race (PRE), at the transitions (T1 and T2), halfway through the run (R21), and after the race (POST; 2hPOST). Core body temperature (T(c); pill telemetry) was recorded continuously, and running speed (s3 stride sensor) was measured during the run. The participant completed the race in 11 h 38 min, in hot conditions (26.6 +/- 5.8 degrees C; 42 +/- 19% rel. humidity). His T(c) increased from 37.0 to 38.6 degrees C during the 57-min swim, and averaged 38.4 degrees C during the 335-min bike (33.5 km x h(-1)). After running at 12.4 km x h(-1) for 50 min in the heat (33.1 degrees C), T(c) increased to 39.4 degrees C, before slowing to 10.0 km x h(-1) for 20 min. T(c) decreased to 38.9 degrees C until he experienced severe leg cramps, after which speed diminished to 6 km x h(-1) and T(c) fell to 38.0 degrees C. The athlete's blood Na(+) was constant from PRE to T2 (139-140 mEq x L(-1), but fell to 131 mEq x L(-1) at R21, 133 mEq x L(-1) at POST, and 128 mEq x L(-1) at 2hPOST. The athlete consumed 9.25 L of fluid from PRE to T2, 6.25 L from T2 to POST, and lost 2% of his body mass, indicating sweat losses greater than 15.5 L. This athlete slowed during the run phase following attainment of a critically high T(c) and experienced an unusually rapid reduction in blood Na(+) that preceded cramping, despite presenting with signs of dehydration.

Rapid diagnosis of occult abscesses using sup 99m Tc-labeled monoclonal antibodies

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

Coons, T.A.; Rhodes, B.A.; Thakur, M.L.

1991-01-01

Acute infections, such as appendicitis and occult infections in AIDS patients, can be diagnosed within two hours by gamma scintigraphy after i.v. administration of {sup 99m}Tc labeled antibodies reactive with human granulocytes. The antibody, murine IgM anti-SSEA-1, is partially reduced using Sn(II) to expose and protect reactive sulfide groups. The antibody is then purified, stannous tartrate and stabilizers are added, and the mixture is lyophilized. To label, sodium pertechnetate is added. After a 15 minute incubation the tracer drug is injected. The rate of accumulation and degree of concentration at the site of infection is presumptively determinative of the severitymore » of the infection. Acceptance criteria and tests for the {sup 99m}Tc labeled antibody product have been established and validated. Greater than 93% of the {sup 99m}Tc is firmly bound to the protein as determined by quantitative HPLC. Radiochemical impurities, colloidal {sup 99m}Tc and free pertechnetate are together less than 4% as determined by thin layer chromatography. The immunoreactive fraction, measured by binding to solid phase antigen, and affinity measured be ELISA, are unchanged by the {sup 99m}Tc-direct labeling process. Two hour blood clearance in rats is within 90% of the value of the {sup 125}I labeled analog. The immunoreactive fraction decreases less than 10% when incubated in human plasma for 24 hours. This method has been compared to other direct labeling methods, and found to give higher radiochemical yields. 5 figs.« less

Electrical behaviour of heterobimetallic [MM'(EtCS2)4] (MM'=NiPd, NiPt, PdPt) and MM'X-chain polymers [PtM(EtCS2)4I] (M=Ni, Pd).

PubMed

Givaja, Gonzalo; Castillo, Oscar; Mateo, Eva; Gallego, Almudena; Gómez-García, Carlos J; Calzolari, Arrigo; di Felice, Rosa; Zamora, Félix

2012-11-26

Herein, we report the isolation of new heterobimetallic complexes [Ni(0.6)Pd(1.4)(EtCS(2))(4)] (1), [NiPt(EtCS(2))(4)] (2) and [Pd(0.4)Pt(1.6)(EtCS(2))(4)] (3), which were constructed by using transmetallation procedures. Subsequent oxidation with iodine furnished the MM'X monodimensional chains [Ni(0.6)Pt(1.4)(EtCS(2))(4)I] (4) and [Ni(0.1)Pd(0.3)Pt(1.6)(EtCS(2))(4)I] (5). The physical properties of these systems were investigated and the chain structures 4 and 5 were found to be reminiscent of the parent [Pt(2)(EtCS(2))(4)I] species. However, they were more sensitively dependent on the localised nature of the charge on the Ni ion, which caused spontaneous breaking of the conduction bands. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nanostructured Ti-Zr-Pd-Si-(Nb) bulk metallic composites: Novel biocompatible materials with superior mechanical strength and elastic recovery.

PubMed

Hynowska, A; Blanquer, A; Pellicer, E; Fornell, J; Suriñach, S; Baró, M D; Gebert, A; Calin, M; Eckert, J; Nogués, C; Ibáñez, E; Barrios, L; Sort, J

2015-11-01

The microstructure, mechanical behaviour, and biocompatibility (cell culture, morphology, and cell adhesion) of nanostructured Ti45 Zr15 Pd35- x Si5 Nbx with x = 0, 5 (at. %) alloys, synthesized by arc melting and subsequent Cu mould suction casting, in the form of rods with 3 mm in diameter, are investigated. Both Ti-Zr-Pd-Si-(Nb) materials show a multi-phase (composite-like) microstructure. The main phase is cubic β-Ti phase (Im3m) but hexagonal α-Ti (P63/mmc), cubic TiPd (Pm3m), cubic PdZr (Fm3m), and hexagonal (Ti, Zr)5 Si3 (P63/mmc) phases are also present. Nanoindentation experiments show that the Ti45 Zr15 Pd30 Si5 Nb5 sample exhibits lower Young's modulus than Ti45 Zr15 Pd35 Si5 . Conversely, Ti45 Zr15 Pd35 Si5 is mechanically harder. Actually, both alloys exhibit larger values of hardness when compared with commercial Ti-40Nb, (HTi-Zr-Pd-Si ≈ 14 GPa, HTi-Zr-Pd-Si-Nb ≈ 10 GPa and HTi-40Nb ≈ 2.7 GPa). Concerning the biological behaviour, preliminary results of cell viability performed on several Ti-Zr-Pd-Si-(Nb) discs indicate that the number of live cells is superior to 94% in both cases. The studied Ti-Zr-Pd-Si-(Nb) bulk metallic system is thus interesting for biomedical applications because of the outstanding mechanical properties (relatively low Young's modulus combined with large hardness), together with the excellent biocompatibility. © 2014 Wiley Periodicals, Inc.

Impact of a Panel of 88 Single Nucleotide Polymorphisms on the Risk of Breast Cancer in High-Risk Women: Results From Two Randomized Tamoxifen Prevention Trials.

PubMed

Cuzick, Jack; Brentnall, Adam R; Segal, Corrinne; Byers, Helen; Reuter, Caroline; Detre, Simone; Lopez-Knowles, Elena; Sestak, Ivana; Howell, Anthony; Powles, Trevor J; Newman, William G; Dowsett, Mitchell

2017-03-01

Purpose At least 94 common single nucleotide polymorphisms (SNPs) are associated with breast cancer. The extent to which an SNP panel can refine risk in women who receive preventive therapy has not been directly assessed previously. Materials and Methods A risk score on the basis of 88 SNPs (SNP88) was investigated in a nested case-control study of women enrolled in the International Breast Intervention Study (IBIS-I) or the Royal Marsden study. A total of 359 women who developed cancer were matched to 636 controls by age, trial, follow-up time, and treatment arm. Genotyping was done using the OncoArray. Conditional logistic regression and matched concordance indices (mC) were used to measure the performance of SNP88 alone and with other breast cancer risk factors assessed using the Tyrer-Cuzick (TC) model. Results SNP88 was predictive of breast cancer risk overall (interquartile range odds ratio [IQ-OR], 1.37; 95% CI, 1.14 to 1.66; mC, 0.55), but mainly for estrogen receptor-positive disease (IQ-OR, 1.44; 95% CI, 1.16 to 1.79; P for heterogeneity = .10) versus estrogen receptor-negative disease. However, the observed risk of SNP88 was only 46% (95% CI, 19% to 74%) of expected. No significant interaction was observed with treatment arm (placebo IQ-OR, 1.46; 95% CI, 1.13 to 1.87; tamoxifen IQ-OR, 1.25; 95% CI, 0.96 to 1.64; P for heterogeneity = .5). The predictive power was similar to the TC model (IQ-OR, 1.45; 95% CI, 1.21 to 1.73; mC, 0.55), but SNP88 was independent of TC (Spearman rank-order correlation, 0.012; P = .7), and when combined multiplicatively, a substantial improvement was seen (IQ-OR, 1.64; 95% CI, 1.36 to 1.97; mC, 0.60). Conclusion A polygenic risk score may be used to refine risk from the TC or similar models in women who are at an elevated risk of breast cancer and considering preventive therapy. Recalibration may be necessary for accurate risk assessment.

Decreased cardiac vagal control in drug-naive patients with panic disorder: a case-control study in Taiwan.

PubMed

Chang, Hsin-An; Chang, Chuan-Chia; Tzeng, Nian-Sheng; Kuo, Terry B J; Lu, Ru-Band; Huang, San-Yuan

2013-06-01

Cardiac autonomic dysregulation has been proposed in panic disorder (PD), but the results are mixed. Analyses with larger sample sizes and better methodology are needed. Forty-eight drug-naïve individuals with PD and 202 healthy volunteers were recruited for a case-control analysis. We used the Hamilton Anxiety Rating Scale and the Beck Anxiety Inventory to assess anxiety severity. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV) parameters. Frequency-domain indices of HRV were obtained. The obtained results were evaluated in association with personality traits assessed by the Tridimensional Personality Questionnaire. Patients exhibited reduced mean RR interval (816.94 ± 135.92 versus 873.47 ± 143.36 ms, P = 0.014) and HRV levels (Var 6.37 ± 1.32 versus 7.38 ± 0.95, LF 4.90 ± 1.63 versus5.82 ± 1.11 and HF 4.57 ± 1.53 versus 5.62 ± 1.24 [ln(ms2)], all P < 0.001) as compared to controls, which mainly suggested a reduction in cardiac vagal control in PD. The anxiety severity was negatively correlated with HRV levels (r = -0.29 for Var, r = -0.22 for LF and r = -0.28 for HF, all P < 0.001). The harm avoidance score (which has been suggested to be associated with serotonergic activity) was associated with decreased HRV levels (r = -0.22 for Var, P < 0.01, r = -0.14 for LF, P < 0.05 and r = -0.17 for HF, P < 0.01). This study demonstrates that PD is associated with cardiac autonomic dysregulation, highlighting the importance of assessing HRV in PD patients. Copyright © 2013 Wiley Publishing Asia Pty Ltd.

Thermodynamic description of Tc(iv) solubility and carbonate complexation in alkaline NaHCO3-Na2CO3-NaCl systems.

PubMed

Baumann, A; Yalçıntaş, E; Gaona, X; Polly, R; Dardenne, K; Prüßmann, T; Rothe, J; Altmaier, M; Geckeis, H

2018-03-28

The solubility of 99 Tc(iv) was investigated in dilute to concentrated carbonate solutions (0.01 M ≤ C tot ≤ 1.0 M, with C tot = [HCO 3 - ] + [CO 3 2- ]) under systematic variation of ionic strength (I = 0.3-5.0 M NaHCO 3 -Na 2 CO 3 -NaCl-NaOH) and pH m (-log[H + ] = 8.5-14.5). Strongly reducing conditions (pe + pH m ≈ 2) were set with Sn(ii). Carbonate enhances the solubility of Tc(iv) in alkaline conditions by up to 3.5 log 10 -units compared to carbonate-free systems. Solvent extraction and XANES confirmed that Tc was kept as +IV during the timeframe of the experiments (≤ 650 days). Solid phase characterization performed by XAFS, XRD, SEM-EDS, chemical analysis and TG-DTA confirmed that TcO 2 ·0.6H 2 O(am) controls the solubility of Tc(iv) under the conditions investigated. Slope analysis of the solubility data in combination with solid/aqueous phase characterization and DFT calculations indicate the predominance of the species Tc(OH) 3 CO 3 - at pH m ≤ 11 and C tot ≥ 0.01 M, for which thermodynamic and activity models are derived. Solubility data obtained above pH m ≈ 11 indicates the formation of previously unreported Tc(iv)-carbonate species, possibly Tc(OH) 4 CO 3 2- , although the likely formation of additional complexes prevents deriving a thermodynamic model valid for this pH m -region. This work provides the most comprehensive thermodynamic dataset available for the system Tc 4+ -Na + -Cl - -OH - -HCO 3 - -CO 3 2- -H 2 O(l) valid under a range of conditions relevant for nuclear waste disposal.

Evaluation of normality and reproducibility parameters of scintigraphy with (99m)Tc-MAA in the diagnosis of intrapulmonary vascular dilatations.

PubMed

de Queirós, Andréa Simone Siqueira; Brandão, Simone Cristina Soares; Macedo, Liana Gonçalves; Ourem, Maira Souto; Mota, Vitor Gomes; Leite, Luiz Arthur Calheiros; Lopes, Edmundo Pessoa Almeida; Domingues, Ana Lúcia Coutinho

2015-01-01

The formation of intrapulmonary vascular dilations (IPVD) is the key event for the onset of hepatopulmonary syndrome, vascular changes secondary to portal hypertension that leads to hypoxemia. The diagnosis of IPVD can be made by contrasted transthoracic echocardiography or scintigraphy with technetium-macroaggregated albumin-((99m)Tc-MAA)-that is a sensitive and specific diagnostic method and quantifies the IPVD magnitude. However, its procedure and diagnostic indices are not yet standardized and well defined in health services. The aims of this study were to define normality values and evaluate the inter- and intra-observer reproducibility degree of diagnostic indexes of IPVD through (99m)Tc-MAA scintigraphy. Cross-sectional study was conducted at the Clinical Hospital, Federal University of Pernambuco (HC-UFPE) between July and December 2012. Fifteen patients with hepatosplenic schistosomiasis and nine patients without liver or heart disease (control group) were assessed. After clinical assessment, ultrasound and echocardiography, patients underwent (99m)Tc-MAA scintigraphy, and a relative brain uptake value exceeding 6 % or systemic uptake value exceeding 11 % was considered diagnostic of IPVD. Each assessment was performed by two independent observers. To analyze the results of the normal group, the nonparametric Bootsptrap method simulation model combined with the Monte Carlo method was used and to analyze inter- and intra-observer reproducibility indexes, the kappa and intra-class correlation coefficient were used. In normal subjects, the average brain uptake of (99m)Tc-MAA was 7.9 ± 0.01 % and systemic uptake was 12.4 ± 0.03 %, with low dispersal rates for both measures. The intra-observer agreement was 100 %, with kappa index of 1.0 (p < 0.0001), suggesting a perfect agreement. The inter-observer agreement was also 100 % (kappa = 1.0, p < 0.0001) for brain uptake; however, systemic uptake showed kappa = 0.25 (p = 0.07), which features tolerable concordance. The intra-class correlation was excellent for both uptake indexes. The normality values were slightly higher than those reported in studies from other countries. The demographic characteristics of the Brazilian population, the small number of patients or different methodologies can be the causes of such differences. (99m)Tc-MAA scintigraphy showed excellent reproducibility.

Study of the structure of yrast bands of neutron-rich 114-124Pd isotopes

NASA Astrophysics Data System (ADS)

Chaudhary, Ritu; Devi, Rani; Khosa, S. K.

2018-02-01

The projected shell model calculations have been carried out in the neutron-rich 114-124Pd isotopic mass chain. The results have been obtained for the deformation systematics of E(2+1) and E(4+1)/E({2}+1) values, BCS subshell occupation numbers, yrast spectra, backbending phenomena, B( E2) transition probabilities and g-factors in these nuclei. The observed systematics of E(2+1) values and R_{42} ratios in the 114-124Pd isotopic mass chain indicate that there is a decrease of collectivity as the neutron number increases from 68 to 78. The occurrence of backbending in these nuclei as well as the changes in the calculated B( E2) transition probabilities and g -factors predict that there are changes in the structure of yrast bands in these nuclei. These changes occur at the spin where there is crossing of g-band by 2-qp bands. The predicted backbendings and predicted values of B( E2)s and g-factors in some of the isotopes need to be confirmed experimentally.

Comparative positron-emission tomography (PET) imaging and phototherapeutic potential of 124I- labeled methyl- 3-(1'-iodobenzyloxyethyl)pyropheophorbide-a vs the corresponding glucose and galactose conjugates.

PubMed

Pandey, Suresh K; Sajjad, Munawwar; Chen, Yihui; Zheng, Xiang; Yao, Rutao; Missert, Joseph R; Batt, Carrie; Nabi, Hani A; Oseroff, Allan R; Pandey, Ravindra K

2009-01-22

In our present study, 3-(1(')-m-iodobenzyloxyethyl)pyropheophorbide-a methyl ester 1, 3-(1'-m-iodobenzyloxyethyl)-17(2)-{(2-deoxy)glucose}pyropheophorbide-a 2, and 3-(1'-m-iodobenzyloxyethyl)-17(2)-{(1-deoxy)galactose}pyropheophorbide-a 3 were synthesized and converted into the corresponding (124)I-labeled analogues by reacting the intermediate trimethyltin analogues with Na(124)I. Photosensitizers 1-3 were evaluated for the PDT efficacy in C3H mice bearing RIF tumors at variable doses and showed a significant long-term tumor cure. Among the compounds investigated, the non-carbohydrate analogue 1 was most effective. These results were in contrast to the in vitro data, where compared to the parent analogue the corresponding galactose and glucose derivatives showed enhanced cell kill. Among the corresponding (124)I-labeled analogues, excellent tumor images were obtained from compound 1 in both tumor models (RIF and Colon-26) and the best tumor contrast was observed at 72 h after injection. Conjugating a glucose moiety to photosensitizer 1 initially diminished its tumor uptake, whereas with time the corresponding galactose analogue showed improved tumor contrast.

Comparative Positron-Emission Tomography (PET) Imaging and Phototherapeutic Potential of 124I- Labeled Methyl- 3-(1′-iodobenzyloxyethyl) pyropheophorbide-a vs. the Corresponding Glucose- and Galactose-Conjugates

PubMed Central

Pandey, Suresh K.; Sajjad, Munawwar; Chen, Yihui; Zheng, Xiang; Yao, Rutao; Missert, Joseph R.; Batt, Carrie; Nabi, Hani A.; Oseroff, Allan R.; Pandey, Ravindra K.

2009-01-01

In our present study, 3-(1′-m-iodobenzyloxyethyl) pyropheophorbide-a methyl ester 1, 3-(1′-m-iodobenzyloxyethyl)-172-{(2-deoxy)glucose} pyropheophorbide-a 2, and 3-(1′-m-iodo benzyloxyethyl)-172-{(1-deoxy)galactose} pyropheophorbide-a 3 were synthesized and converted into the corresponding 124I- labeled analogs by reacting the intermediate trimethyltin analogs with Na124I. Photosensitizers 1–3 were evaluated for the PDT efficacy in C3H mice bearing RIF tumors at variable doses and showed a significant long-term tumor cure. Among the compounds investigated, the non-carbohydrate analog 1 was most effective. These results were in contrast to the in vitro data, where compared to the parent analog the corresponding galactose-and glucose derivatives showed enhanced cell kill. Among the corresponding 124I-labeled in analogs, excellent tumor images were obtained from compound 1 both tumor models (RIF and Colon-26) and the best tumor contrast was observed at 72 h post injection. Conjugating a glucose moiety to photosensitizer 1 diminished its tumor uptake, whereas with time the corresponding galactose analog showed improved tumor contrast. PMID:19090663

Tropical Cyclone Report, 1992

DTIC Science & Technology

1992-01-01

19S Davilia 6 0 0 6 TC 20S Harriet 137 0 0 137 TC 21P Esau iII 0 0 i1 TC 22S Farida 36 0 0 36 TC 23S Ian 79 0 0 79 TC 24S Gerda 15 0 0 15 TC 25P Fran...13 115(60) 927 24S Gerda 27 Feb - 28 Feb 3 35(18) 997 25P Fran* 06 Mar - 17 Mar 23 140(72) 898 26P Gene 15 Mar - 19 Mar 9 65(33) 976 27P Hettie 25 Mar...CYCLONE 24S ( GERDA ) WRN BEST TRACK POSITION ERRORS WIND ERRORS M NO. LT NM WID 2A Al U 72 Z Al Ui 92022718 1 15.9S 61.7E 35 8 67 160 0 20 35 92022806 2

Intranasal Insulin: A Novel Treatment for Gulf War Multisymptom Illness

DTIC Science & Technology

2013-10-01

pyridostigmine bromide . Fort Detrick, MD: US Army Medical Research and Material Command. Li B, Mahan CM, Kang HK, Eisen SA, Engel CC. (2011, July 27...Sullivan K, Krengel M, Proctor SP, Devine S, Heeren T, White RF. (2003). Cognitive functioning in treatment-seeking Gulf War veterans: pyridostigmine ... bromide use and PTSD. Journal of Psychopathology and Behavioral Assessment. 25(2):95-103. Tillman GD, Green TA, Ferree TC, Calley CS, Maguire MJ

Tripodal polyphosphine ligands as inductors of chelate ring-opening processes in mononuclear palladium(II) and platinum(II) compounds. The X-ray crystal structure of two derivatives containing dangling phosphorus.

PubMed

Fernández-Anca, Damián; García-Seijo, M Inés; García-Fernández, M Esther

2010-03-07

The reaction of NP(3) (tris[2-(diphenylphosphino)ethyl]amine and PP(3) (tris[2-(diphenylphosphino)ethyl]phosphine) with the five-coordinate complexes [PdCl(NP(3))]Cl (1) and [MX(PP(3))]X [M = Pd: X = Cl(2), Br(3), I(4); M = Pt: X = Cl(5), Br(6), I(7)], respectively, followed by (31)P{(1)H}NMR when X = Cl, led to the formation of unprecedented four-coordinate halides in a 1 : 2 metal to ligand ratio, [M(AP(3))(2)]X(2) [A = N, M = Pd: X = Cl(8); A = P, M = Pd: X = Cl(9), Br(10), I(11); A = P, M = Pt: X = Cl(12), Br(13), I (14)], containing reactive dangling phosphorus. Given the non characterised precursors [M(ONO(2))(PP(3))](NO(3))], the interaction between the heteronuclear species [MAg(NO(3))(3)(PP(3))] [M = Pd(15), Pt(16)] and PP(3) was explored. It was found that the addition of 1 equivalent of phosphine afforded [MAg(NO(3))(PP(3))(2)](NO(3))(2) [M = Pd(15*), Pt(16*)] containing Ag(I) bound to two dangling phosphorus while the reaction with 2 equivalents led to the complexes [M(PP(3))(2)](NO(3))(2) [M = Pd (17), Pt (18)] in coexistence with [Ag(2)(mu-PP(3))(2)](NO(3))(2). The fate of Ag(I) on the reaction of the mixed metal compounds with excess PP(3) consisted of preventing dissociation, observed in solution for halides, and acting as an assistant for crystallization. Colourless single crystals of 18 and 10, studied by X-ray diffraction, were afforded by reaction of 16 with 4 equivalents of PP(3) and from solutions of 10 in chloroform coexisting with red crystals of 3, respectively. The structures revealed the presence of dications [M(PP(3))(2)](2+) that show two five-membered chelate rings to M(II) in a square-planar arrangement and four uncoordinated phosphine arms with the counter anions being symmetrically placed at 4.431 (Br(-)) and 13.823 (NO(3)(-)) A from M(II) above and below its coordination, MP(4), plane. Complexes 9 and 12 were shown to undergo an interesting reactivity in solution versus group 11 monocations. The reactions consisted of conversions of the two five-membered chelate rings to M into three (structure I) or two (structure II) fused five-membered chelate rings, formation of species where Pt(II) retained its square-planar environment with the two dangling phosphine arms of each PP(3) bound to Cu(I) or Ag(I) (structure III) and complexes bearing distorted square-planar (P(2)MCl(2)) and presumably tetrahedral (AuP(4)+ P(2)AuCl(2)) arrangements (structure IV). The processes with Ag(I) salts also gave mixtures of I+III (chloride and nitrate) or II+III (nitrate).

Mannosylated dextran derivatives labeled with fac-[M(CO)₃]+ (M = (99m)Tc, Re) for specific targeting of sentinel lymph node.

PubMed

Morais, Maurício; Subramanian, Suresh; Pandey, Usha; Samuel, Grace; Venkatesh, Meera; Martins, Manuel; Pereira, Sérgio; Correia, João D G; Santos, Isabel

2011-04-04

Despite being widely used in the clinical setting for sentinel lymph node detection (SLND), (99m)Tc-based colloids (e.g., (99m)Tc-human serum albumin colloids) present a set of properties that are far from ideal. Aiming to design novel compounds with improved biological properties, we describe herein the first class of fully characterized (99m)Tc(CO)₃-mannosylated dextran derivatives with adequate features for SLND. Dextran derivatives, containing the same number of pendant mannose units (13) and a variable number (n) of tridentate chelators (9, n = 1; 10, n = 4, 11, n= 12), have been synthesized and fully characterized. Radiolabeled polymers of the type fac-[(99m)Tc(CO)₃(k³-L)] (12, L = 9, 13, L = 10, 14, L = 11) have been obtained quantitatively in high radiochemical purity (≥ 98%) upon reaction of the dextran derivatives with fac-[(99m)Tc(CO)₃(H₂O)₃]+. The highly stable compounds 13 and 14 were identified by comparing their HPLC chromatograms with the ones obtained for the corresponding rhenium surrogates fac-[Re(CO)₃(k³-10)] (13a) and fac-[Re(CO)₃(k³-11)] (14a), which have been characterized both at the chemical (NMR and IR spectroscopy, and HPLC) and physical level (DLS, AFM and LDV). Compounds 13a and 14a present a positive zeta potential (+ 7.1 mV, pH 7.4) and a hydrodynamic diameter in the range 8.4-8.7 nm. Scintigraphic imaging and biodistribution studies in Wistar rats have shown good accumulation in the sentinel node at 60 min postinjection (6.71 ± 2.35%, 13; and 7.53 ± 0.69%, 14), with significant retention up to 180 min. A clear delineation of the sentinel lymph node without significant washout to other regions was observed in the scintigraphic images. The popliteal extraction of 94.47 ± 2.45% for 14 at 1 h postinjection, as compared to 61.81 ± 2.4% for 13, indicated that 14 is a very promising compound to be further explored as SLN imaging agent.

The effect of boric acid on acethylcholine, bethanechol and potasssium-evoked responses on ileum of rat.

PubMed

Ince, S; Turkmen, R; Yavuz, H

2011-01-01

1 The aim of this study was to clarify the effect of boric acid on contractions of rat isolated ileum. 2 Contractile responses expressed as Emax and pD2 for acetylcholine (10(-3)-10(-8) m, Ach), bethanechol (10(-3)-10(-8) m) and potassium (10-80 × 10(-3) m, KCl) were determined in the absence and presence of boric acid (10(-3); 5 × 10(-4); 10(-4) m). 3 The contractile response to Ach in the presence of verapamil (10(-6) or 10(-8) m) or in calcium-free Tyrode's solution was also determined in the absence and presence of boric acid. 4 Boric acid did not affect the contractile response to Ach, bethanechol or KCl. Single or cumulative treatment of boric acid did not affect ileum muscle contraction evoked by KCl. The atropine-resistant component of Ach-induced contraction and 4-diphenyl-acetoxy-N-methyl-piperidine methiodide-resistant component of bethanechol-induced contraction were not inhibited by boric acid (10(-3) m). The contractile response to Ach was reduced in calcium-free Tyrode's solution, and the contractile response was not affected by (10(-8) m). The addition of boric acid (10(-3) m) in combination with verapamil (10(-8) m) did not significantly affect the contractile response to Ach. 5 In conclusion, boric acid does not affect contractions induced by Ach, bethanechol or potassium in rat isolated ileum. © 2011 Blackwell Publishing Ltd.

Early detection of probable idiopathic Parkinson's disease: I. development of a diagnostic test battery.

PubMed

Montgomery, Erwin B; Koller, William C; LaMantia, Theodora J K; Newman, Mary C; Swanson-Hyland, Elizabeth; Kaszniak, Alfred W; Lyons, Kelly

2000-05-01

We developed a test battery as an inexpensive and objective aid for the early diagnosis of idiopathic Parkinson's disease (iPD) and its differential diagnoses. The test battery incorporates tests of motor function, olfaction, and mood. In the motor task, a wrist flexion-and-extension task to different targets, movement velocities were recorded. Olfaction was tested with the University of Pennsylvania Smell Identification Test. Mood was assessed with the Beck Depression Inventory. An initial regression model was developed from the results of 19 normal control subjects and 18 patients with early, mild, probable iPD. Prospective application to an independent validation set of 122 normal control subjects and 103 patients resulted in an 88% specificity rate and 69% sensitivity rate, with an area under the Receiver Operator Characteristic curve of 0.87. Copyright © 2000 Movement Disorder Society.

Testosterone Deficiency and Bone Metabolism Damage in Testicular Cancer Survivors

PubMed Central

Ondrusova, Martina; Spanikova, Beata; Sevcikova, Katarina; Ondrus, Dalibor

2016-01-01

The aim of the study was to investigate the influence of therapeutic modalities and sexual hormone levels on changes in bone mineral density (BMD) in testicular cancer (TC) survivors. In a cross-sectional descriptive, long-term follow-up study, a total of 1,249 long-term TC survivors were evaluated according to treatment modality: orchiectomy (OE) only, OE + chemotherapy (CT), or OE + radiotherapy (RT). Luteinizing hormone (LH), total testosterone (TST), marker of bone resorption (β-carboxyl-terminal cross-linking telopeptide of type I collagen—CTx), and BMD were evaluated. Standard statistical techniques were used to test the differences between groups of patients. TST decrease was observed in 46/313 TC survivors after OE alone, in 103/665 after OE + CT, and in 66/271 after OE + RT. LH increase was observed in 23/313 TC survivors after OE alone, in 154/665 after OE + CT, and in 43/271 after OE + RT. CTx increase was observed in 116/313 TC survivors after OE alone, in 324/665 after OE + CT, and in 82/271 after OE + RT. Osteopenia/osteoporosis occurred in 136/313 TC survivors after OE alone, in 298/665 after OE + CT, and in 139/271 after OE + RT. TC survivors after RT have statistically significant decreased TST levels, increased LH and nonsignificant worse BMD (osteopenia/osteoporosis) in comparison with TC survivors after OE alone or CT. TST decrease and LH increase were statistically significant, more frequently observed in patients with osteopenia/osteoporosis. Examination of TST is an important part of follow-up in TC survivors with bilateral as well as unilateral disease. The important part of standard examination algorithm should be also the osteological examination of TC survivors mainly in patients with androgen deficiency. PMID:27489147

The effect of sodium pertechnetate human carbonic anhydrase I and II

NASA Astrophysics Data System (ADS)

Sahin, Ali; Senturk, Murat

2017-04-01

The inhibitory effects of Na99mTcO4 (Sodium pertechnetate) on human erythrocyte carbonic anhydrase I and II activity were investigated. For this purpose, hCA I was initially purified 114,29-fold at a yield of 69,19 % and hCA II was initially purified 710,82-fold at a yield of 71,72 % using sepharose 4B-tyrosine-sulfanilamide affinity gel chromatography. The in vitro effect of this compound on hCA I and II isoenzyme were studied. It was detected in in vitro studies that the hCA I and II enzymes are inhibited due to Na99mTcO4.

Development of a PD-L1 Complementary Diagnostic Immunohistochemistry Assay (SP142) for Atezolizumab.

PubMed

Vennapusa, Bharathi; Baker, Brian; Kowanetz, Marcin; Boone, Jennifer; Menzl, Ina; Bruey, Jean-Marie; Fine, Gregg; Mariathasan, Sanjeev; McCaffery, Ian; Mocci, Simonetta; Rost, Sandra; Smith, Dustin; Dennis, Eslie; Tang, Szu-Yu; Damadzadeh, Bita; Walker, Espen; Hegde, Priti S; Williams, J Andrew; Koeppen, Hartmut; Boyd, Zachary

2018-01-16

Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non-small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues. The reader precision, repeatability and intermediate precision, interlaboratory reproducibility, and the effectiveness of pathologist training on the assessment of PD-L1 staining on both TC and IC were evaluated. We detail the analytical validation of the VENTANA PD-L1 (SP142) Assay for PD-L1 expression in NSCLC and UC tissues and show that the assay reliably evaluated staining on both TC and IC across multiple expression levels/clinical cut-offs. The reader precision showed high overall agreement when compared with consensus scores. In addition, pathologists met the predefined training criteria (≥85.0% overall percent agreement) for the assessment of PD-L1 expression in NSCLC and UC tissues with an average overall percent agreement ≥95.0%. The assay evaluates PD-L1 staining on both cell types and is robust and precise. In addition, it can help to identify those patients who may benefit the most from treatment with atezolizumab, although treatment benefit has been demonstrated in an all-comer NSCLC and UC patient population.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

Electrochemical biosensor based on glucose oxidase encapsulated within enzymatically synthesized poly(1,10-phenanthroline-5,6-dione).

PubMed

Ciftci, Hakan; Oztekin, Yasemin; Tamer, Ugur; Ramanaviciene, Almira; Ramanavicius, Arunas

2014-11-01

This study is focused on the investigation of electrocatalytic effect of glucose oxidase (GOx) immobilized on the graphite rod (GR) electrode. The enzyme modified electrode was prepared by encapsulation of immobilized GOx within enzymatically formed poly(1,10-phenanthroline-5,6-dione) (pPD) film. The electrochemical responses of such enzymatic electrode (pPD/GOx/GR) vs. different glucose concentrations were examined chronoamperometrically in acetate-phosphate buffer solution (A-PBS), pH 6.0, under aerobic or anaerobic conditions. Amperometric signals of the pPD/GOx/GR electrode exhibited well-defined hyperbolic dependence upon glucose concentration. Amperometric signals at 100mM of glucose were 41.17 and 32.27 μA under aerobic and anaerobic conditions, respectively. Amperometric signals of the pPD/GOx/GR electrode decreased by 6% within seven days. The pPD/GOx/GR electrode showed excellent selectivity in the presence of dopamine and uric acid. Furthermore it had a good reproducibility and repeatability with standard deviation of 9.4% and 8.0%, respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

Report of a nationwide survey on actual administered radioactivities of radiopharmaceuticals for diagnostic reference levels in Japan.

PubMed

Watanabe, Hiroshi; Ishii, Kazunari; Hosono, Makoto; Imabayashi, Etsuko; Abe, Koichiro; Inubushi, Masayuki; Ohno, Kazuko; Magata, Yasuhiro; Ono, Kinya; Kikuchi, Kei; Wagatsuma, Kei; Takase, Tadashi; Saito, Kyoko; Takahashi, Yasuyuki

2016-07-01

The optimization of medical exposure is one of the major issues regarding radiation protection in the world, and The International Committee of Radiological Protection and the International Atomic Energy Agency recommend establishing diagnostic reference levels (DRLs) as tools for dose optimization. Therefore, the development of DRLs based on the latest survey has been required for nuclear medicine-related societies and organizations. This prompted us to conduct a nationwide survey on the actual administered radioactivity to adults for the purpose of developing DRLs in nuclear medicine. A nationwide survey was conducted from November 25, 2014 to January 16, 2015. The questionnaire was sent to all of the 1249 nuclear medicine facilities in Japan, and the responses were collected on a website using an answered form. Responses were obtained from 516 facilities, for a response rate of 41 %. 75th percentile of (99m)Tc-MDP and (99m)Tc-HMDP: bone scintigraphy, (99m)Tc-HM-PAO, (99m)Tc-ECD and (123)I-IMP: cerebral blood flow scintigraphy, (99m)Tc-Tetrofosmin, (99m)Tc-MIBI and (201)Tl-Cl; myocardial perfusion scintigraphy and (18)F-FDG: oncology PET (in-house-produced or delivery) in representative diagnostic nuclear medicine scans were 932, 937, 763, 775, 200, 831, 818, 180, 235 and 252, respectively. More than 90 % of the facilities were within the range of 50 % from the median of these survey results in representative diagnostic nuclear medicine facilities in Japan. Responses of the administered radioactivities recommended by the package insert, texts and guidelines such as 740 MBq ((99m)Tc-MDP and (99m)Tc-HMDP: bone scintigraphy), 740 MBq ((99m)Tc-ECD and (99m)Tc-HM-PAO: cerebral blood flow scintigraphy) and 740 MBq ((99m)Tc-Tetrofosmin and (99m)Tc-MIBI: myocardial perfusion scintigraphy), etc. were numerous. The administered activity of many radiopharmaceuticals of bone scintigraphy ((99m)Tc-MDP and (99m)Tc-HMDP), cerebral blood flow scintigraphy ((99m)Tc-HM-PAO) and myocardial perfusion scintigraphy ((99m)Tc-Tetrofosmin and (99m)Tc-MIBI), etc. were within the range of the EU DRLs and almost none of the administered radioactivity in Japan exceeded the upper limit of SNMMI standard administered radioactivity. This survey indicated that the administered radioactivity in diagnostic nuclear medicine in Japan had been in the convergence zone and nuclear medicine facilities in Japan show a strong tendency to adhere to the texts and guidelines. Furthermore, the administered radioactivities in Japan were within the range of variation of the EU and the SNMMI administered radioactivities.

Ft. Benning, Georgia. Revised Uniform Summary of Surface Weather Observations. Parts A-F.

DTIC Science & Technology

1987-09-01

92.4 GE 27001 1 . 2 93.4 94.6 4 4. 94 . .1 95.1 95.1 45. 1 95.1 95.1 95.1 95.1 95.1 95.1 GE 1801 91.6 94.2 96.1 95.4 j.4 ,.7 95.7 95.7 95.7 95.7 95.7...300 310 3651 0 ISO .191 .192 .204 .147 .110 .088 .073 .078 .103 .119 .151 .182 .153 1,01 oJsI 310 282 3P18 31 310 300 310 110 300 310 300 310 3650 ME~l

A mutant screening method by critical annealing temperature-PCR for site-directed mutagenesis.

PubMed

Liu, Ying; Wu, Ting; Song, Jian; Chen, Xuelian; Zhang, Yu; Wan, Yu

2013-03-11

Distinguishing desired mutants from parental templates and undesired mutants is a problem not well solved in Quikchange™ mutagenesis. Although Dpn I digestion can eliminate methylated parental (WT) DNA, the efficiency is not satisfying due to the existence of hemi-methylated DNA in the PCR products, which is resistant to Dpn I. The present study designed a novel critical annealing temperature (T(c))-PCR to replace Dpn I digestion for more perfect mutant distinguishing, in which part-overlapping primers containing mutation(s) were used to reduce initial concentration of template DNA in mutagenic PCR. A T(c)-PCR with the same mutagenic primers was performed without Dpn I digestion. The T(c) for each pair of the primers was identified by gradient PCR. The relationship between PCR-identified T(c) and T(m) of the primers was analyzed and modeled with correlation and regression. Gradient PCR identified a T(c) for each of 14 tested mutagenic primers, which could discriminate mismatched parental molecules and undesired mutants from desired mutants. The PCR-identified T(c) was correlated to the primer's T(m) (r = 0.804, P<0.0001). Thus, in practical applications, the T(c) can be easily calculated with a regression equation, T(c)= 48.81 + 0.253*T(m). The new protocol introduced a novel T(c)-PCR method for mutant screening which can more efficiently and accurately select against parental molecules and undesired mutations in mutagenic sequence segments.

A photon spectrometric dose-rate constant determination for the Advantage Pd-103 brachytherapy source

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

Chen, Zhe Jay; Bongiorni, Paul; Nath, Ravinder

Purpose: Although several dosimetric characterizations using Monte Carlo simulation and thermoluminescent dosimetry (TLD) have been reported for the new Advantage Pd-103 source (IsoAid, LLC, Port Richey, FL), no AAPM consensus value has been established for the dosimetric parameters of the source. The aim of this work was to perform an additional dose-rate constant ({Lambda}) determination using a recently established photon spectrometry technique (PST) that is independent of the published TLD and Monte Carlo techniques. Methods: Three Model IAPD-103A Advantage Pd-103 sources were used in this study. The relative photon energy spectrum emitted by each source along the transverse axis wasmore » measured using a high-resolution germanium spectrometer designed for low-energy photons. For each source, the dose-rate constant was determined from its emitted energy spectrum. The PST-determined dose-rate constant ({sub PST}{Lambda}) was then compared to those determined by TLD ({sub TLD}{Lambda}) and Monte Carlo ({sub MC}{Lambda}) techniques. A likely consensus {Lambda} value was estimated as the arithmetic mean of the average {Lambda} values determined by each of three different techniques. Results: The average {sub PST}{Lambda} value for the three Advantage sources was found to be (0.676{+-}0.026) cGyh{sup -1} U{sup -1}. Intersource variation in {sub PST}{Lambda} was less than 0.01%. The {sub PST}{Lambda} was within 2% of the reported {sub MC}{Lambda} values determined by PTRAN, EGSnrc, and MCNP5 codes. It was 3.4% lower than the reported {sub TLD}{Lambda}. A likely consensus {Lambda} value was estimated to be (0.688{+-}0.026) cGyh{sup -1} U{sup -1}, similar to the AAPM consensus values recommended currently for the Theragenics (Buford, GA) Model 200 (0.686{+-}0.033) cGyh{sup -1} U{sup -1}, the NASI (Chatsworth, CA) Model MED3633 (0.688{+-}0.033) cGyh{sup -1} U{sup -1}, and the Best Medical (Springfield, VA) Model 2335 (0.685{+-}0.033) cGyh{sup -1} U{sup -1} {sup 103}Pd sources. Conclusions: An independent {Lambda} determination has been performed for the Advantage Pd-103 source. The {sub PST}{Lambda} obtained in this work provides additional information needed for establishing a more accurate consensus {Lambda} value for the Advantage Pd-103 source.« less

Nuclear Data Sheets for A = 92

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

Baglin, Coral M.

2012-10-15

Nuclear structure and decay data pertaining to all nuclides with mass number A = 92 (As, Se, Br, Kr, Rb, Sr, Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd) have been compiled and evaluated, and incorporated into the ENSDF data file. All literature available by 15 September 2012 has been considered. This evaluation supersedes the previous publication for this mass chain (Coral M. Baglin, Nuclear Data Sheets 91, 423 (2000) (November 2000 cutoff date)), and subsequent unpublished reevaluations by C.M. Baglin for {sup 92}Kr (January 2004 literature cut-off) and {sup 92}Sr (August 2003 literature cut-off).

Comparative NMR studies of diffusional water permeability of red blood cells from different species: XVIII platypus (Ornithorhynchus anatinus) and saltwater crocodile (Crocodylus porosus).

PubMed

Benga, Gheorghe; Chapman, Bogdan E; Cox, Guy C; Kuchel, Philip W

2010-07-01

As part of a programme of comparative measurements of Pd (diffusional water permeability) the RBCs (red blood cells) from an aquatic monotreme, platypus (Ornithorhynchus anatinus), and an aquatic reptile, saltwater crocodile (Crocodylus porosus) were studied. The mean diameter of platypus RBCs was estimated by light microscopy and found to be approximately 6.3 microm. Pd was measured by using an Mn2+-doping 1H NMR (nuclear magnetic resonance) technique. The Pd (cm/s) values were relatively low: approximately 2.1 x 10(-3) at 25 degrees C, 2.5 x 10(-3) at 30 degrees C, 3.4 x 10(-3) at 37 degrees C and 4.5 at 42 degrees C for the platypus RBCs and approximately 2.8 x 10(-3) at 25 degrees C, 3.2 x 10(-3) at 30 degrees C, 4.5 x 10(-3) at 37 degrees C and 5.7 x 10(-3) at 42 degrees C for the crocodile RBCs. In parallel with the low water permeability, the Ea,d (activation energy of water diffusion) was relatively high, approximately 35 kJ/mol. These results suggest that "conventional" WCPs (water channel proteins), or AQPs (aquaporins), are probably absent from the plasma membranes of RBCs from both the platypus and the saltwater crocodile.

Comparison of 99mTc-HYNIC-TOC and HYNIC-TATE octreotide scintigraphy with FDG PET and 99mTc-MIBI in local recurrent or distant metastatic thyroid cancers.

PubMed

Sager, Sait; Kabasakal, Levent; Halac, Metin; Maecke, Helmut; Uslu, Lebriz; Önsel, Çetin; Kanmaz, Bedii

2013-05-01

There have been various studies for early diagnosis of local recurrent or distant metastatic thyroid cancers. The aim of this study is to evaluate the clinical utility of 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE, octreotide derivatives, to detect recurrences or distant metastases in 131I-negative thyroglobulin positive thyroid cancer patients and to compare the lesions with FDG PET and 99mTc-MIBI studies in the same patient group. Twenty differentiated thyroid cancer patients, 7 male and 13 female, mean age 54.6 ± 15.3 (range 13-78 years), were included in this study. Eighteen patients had papillary thyroid cancer and 2 had follicular thyroid cancer. Fifteen patients received HYNIC-TOC and 5 patients received HYNIC-TATE as a radiopharmaceutical. All patients underwent whole-body scan 1 and 4 hours after injection of octreotide derivatives and SPECT imagings were performed from the suspicious sites. The lesions that were seen in 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE studies were compared with 99mTc-MIBI and FDG-PET studies. Among 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE scintigraphies, 15 patient studies were evaluated as true positive (75%) and 5 were false negative (25%). The total number of lesions in octreotide scintigraphy was 48 in 20 patients. Of 20 patients, 19 had FDG-PET study, 15 of them were evaluated as true positive (78.9%), and 4 them were evaluated as false negative (21.1%). Total number of lesions in FDG PET was 74. 99mTc-MIBI study was positive in 11 patients (55%) and negative in 9 patients (45%). Total number of lesions in 99mTc-MIBI was 25. Technetium-labeled somatostatin receptor scintigraphy analogues HYNIC-TOC and HYNIC-TATE are useful imaging alternatives in somatostatin receptor expressing thyroid cancer patients. Radiolabeling is easy and they are readily available for routine use.

[Preparation, quality control and thyroid molecule imaging of solid-target based radionuclide ioine-124].

PubMed

Zhu, H; Wang, F; Guo, X Y; Li, L Q; Duan, D B; Liu, Z B; Yang, Z

2018-04-18

To provide useful information for the further production and application of this novel radio-nuclide for potential clinical application. 124 Te (p,n) 124 I nuclide reaction was used for the 124 I production. Firstly, the target material, 124 TeO 2 (200 mg) and Al2O3 (30 mg) mixture, were compressed into the round platinum based solid target by tablet device. HM-20 medical cyclotron was applied to irradiate the solid target slice for 6-10 h with helium and water cooling. Then, the radiated solid target was placed for 12 h (overnight) to decay the radioactive impurity; finally, 124 I was be purified by dry distillation using 1 mL/min nitrogen for about 6 hours and radiochemical separation methods. Micro-PET imaging studies were performed to investigate the metabolism properties and thyroid imaging ability of 124 I.After 740 kBq 124 I was injected intravenously into the tail vein of the normal mice, the animals were imaged with micro-PET and infused with CT. The micro-PET/CT infusion imaging revealed actual state 124 I's metabolism in the mice. It was been successfully applied for 200 mg 124 TeO 2 plating by the tablet device on the surface of platinum. It showed smooth, dense surface and without obviously pits and cracks. The enriched 124 Te target was irradiated for 6 to 10 hours at about 12.0 MeV with 20 μA current on HM-20 cyclotron. Then 370-1 110 MBq 124 I could be produced on the solid target after irradiation and 370-740 MBq high specific activity could be collected afterdry distillation separation and radio-chemical purification. 124 I product was finally dissolved in 0.01 mol/L NaOH for the future distribution. The gamma spectrum of the produced 124 I-solution showed that radionuclide purity was over 80.0%. The micro-PET imaging of 124 I in the normal mice exhibited the thyroid and stomach accumulations and kidney metabolism, the bladder could also be clearly visible, which was in accordance with what was previously reported. To the best of our knowledge, it was the first production of 124 I report in China. In this study, the preparation of 124 TeO 2 solid target was successfully carried out by using the tablet device. After irradiation of the 124 TeO 2 solid target and radio-chemical purification, we successfully produced 370-740 MBq high specific activity 124 I by a cyclotron for biomedical application, and micro-PET imaging of 124 I in normal mice exhibited the thyroid accumulations. Also, slight uptake in stomach were also monitored with almost nonuptake in other organs in the micro-PET imaging. The production of 124 I is expected to provide a new solid target radionuclide for the scientific research and potential clinical application of our country.

KSC-08pd1743

NASA Image and Video Library

2008-06-14

CAPE CANAVERAL, Fla. – Following the successful landing of space shuttle Discovery at NASA's Kennedy Space Center to end the 14-day, STS-124 mission, the crew sits for a press conference. Mission Specialist Ron Garan describes his favorite view from orbit. The mission delivered the Japan Aerospace Exploration Agency's large Japanese Pressurized Module and its remote manipulator system to the International Space Station. The landing was on time at 11:15 a.m. EDT. Photo credit: NASA/Kim Shiflett

Quantitative analysis of [99mTc]C2A-GST distribution in the area at risk after myocardial ischemia and reperfusion using a compartmental model.

PubMed

Audi, Said; Poellmann, Michael; Zhu, Xiaoguang; Li, Zhixin; Zhao, Ming

2007-11-01

It was recently demonstrated that the radiolabeled C2A domain of synaptotagmin I accumulates avidly in the area at risk after ischemia and reperfusion. The objective was to quantitatively characterize the dynamic uptake of radiolabeled C2A in normal and ischemically injured myocardia using a compartmental model. To induce acute myocardial infarction, the left descending coronary artery was ligated for 18 min, followed by reperfusion. [99mTc]C2A-GST or its inactivated form, [99mTc]C2A-GST-NHS, was injected intravenously at 2 h after reperfusion. A group of four rats was sacrificed at 10, 30, 60 and 180 after injection. Uptake of [99mTc]C2A-GST and [99mTc]C2A-GST-NHS in the area at risk and in the normal myocardium were determined by gamma counting. A compartmental model was developed to quantitatively interpret myocardial uptake kinetic data. The model consists of two physical spaces (vascular space and tissue space), with plasma activity as input. The model allows for [99mTc]C2A-GST and [99mTc]C2A-GST-NHS diffusion between vascular and tissue spaces, as well as for [99mTc]C2A-GST sequestration in vascular and tissue spaces via specific binding. [99mTc]C2A-GST uptake in the area at risk was significantly higher than that for [99mTc]C2A-GST-NHS at all time points. The compartmental model separated [99mTc]C2A-GST uptake in the area at risk due to passive retention from that due to specific binding. The maximum amount of [99mTc]C2A-GST that could be sequestered in the area at risk due to specific binding was estimated at a total of 0.048 nmol/g tissue. The rate of [99mTc]C2A-GST sequestration within the tissue space of the area at risk was 0.012 ml/min. Modeling results also revealed that the diffusion rate of radiotracer between vascular and tissue spaces is the limiting factor of [99mTc]C2A-GST sequestration within the tissue space of the area at risk. [99mTc]C2A-GST is sequestered in the ischemically injured myocardium in a well-defined dynamic profile. Model parameters will be valuable indicators for gauging and guiding the development of future-generation molecular probes.

Performance characteristics of dedicated molecular breast imaging systems at low doses

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

Long, Zaiyang; Conners, Amy L.; Hunt, Katie N.

Purpose: The purpose of this study was to compare the system performance characteristics and lesion detection capability of two molecular breast imaging (MBI) systems: a multicrystal sodium iodide (NaI)-based single-head system and a cadmium zinc telluride (CZT)-based dual-head system at low administered doses (150–300 MBq) of Tc-99m sestamibi. Methods: System performance characteristics including count sensitivity, uniformity, energy resolution, and spatial resolution were measured using standard NEMA methods, or a modified version thereof in cases where the standard NEMA protocol could not be applied. A contrast-detail phantom with 48 lesions at varying depths from the collimator surface was used to assessmore » lesion contrast-to-noise-ratio (CNR) using background count densities comparable to those observed in patient studies performed with administered doses of 150 MBq Tc-99m sestamibi. Lesions with CNR >3 were deemed to be detectable. Thirty patients undergoing MBI examinations with administered doses of 150–300 MBq were scanned for an additional view on the pixelated NaI system. CNR was calculated for lesions observed on patient images. Background count densities of patient images were measured and compared between the two systems. Results: Over the central field of view, integral and differential uniformity were 6.1% and 4.2%, respectively, for the pixelated NaI system, and 3.8% and 2.7%, respectively, for the CZT system. Count sensitivity was 10.8 kcts/min/MBq for the NaI system and 32.9 kcts/min/MBq for the CZT system. Energy resolution was 13.5% on the pixelated NaI system and 4.5% on the CZT system. Spatial resolution (full-width at half-maximum) for the pixelated NaI detector was 4.2 mm at a distance of 1.2 cm from the collimator and 5.2 mm at 3.1 cm. Spatial resolution of a single CZT detector was 2.9 mm at a distance of 1.2 cm from the collimator and 4.7 mm at 3.1 cm. Effective spatial resolution obtained with dual-head CZT was below 4.7 mm throughout a simulated breast thickness of 6 cm. From contrast-detail phantom images of lesions at distances of 1.5–4.5 cm from the collimator face, the CZT system detected 124 of 144 (86%) of lesions compared to 97 of 144 (67%) with the NaI system. In patient studies, from comparison of the same view with both systems, a total of 7 breast lesions were identified on CZT system in seven patients, and 4 of 7 (57%) were detected on NaI system. Patient image background count densities on the CZT system were on average 3.4 times higher than those on the NaI system. Conclusions: The CZT system demonstrated better uniformity, count sensitivity, spatial resolution, energy resolution, and lesion detection in phantom and patient studies compared to the NaI system. At administered doses of 150–300 MBq Tc-99m sestamibi, patient results obtained with CZT systems may not be directly translatable to NaI systems.« less

Organization and variation analysis of 5S rDNA in different ploidy-level hybrids of red crucian carp × topmouth culter.

PubMed

He, Weiguo; Qin, Qinbo; Liu, Shaojun; Li, Tangluo; Wang, Jing; Xiao, Jun; Xie, Lihua; Zhang, Chun; Liu, Yun

2012-01-01

Through distant crossing, diploid, triploid and tetraploid hybrids of red crucian carp (Carassius auratus red var., RCC♀, Cyprininae, 2n = 100) × topmouth culter (Erythroculter ilishaeformis Bleeker, TC♂, Cultrinae, 2n = 48) were successfully produced. Diploid hybrids possessed 74 chromosomes with one set from RCC and one set from TC; triploid hybrids harbored 124 chromosomes with two sets from RCC and one set from TC; tetraploid hybrids had 148 chromosomes with two sets from RCC and two sets from TC. The 5S rDNA of the three different ploidy-level hybrids and their parents were sequenced and analyzed. There were three monomeric 5S rDNA classes (designated class I: 203 bp; class II: 340 bp; and class III: 477 bp) in RCC and two monomeric 5S rDNA classes (designated class IV: 188 bp, and class V: 286 bp) in TC. In the hybrid offspring, diploid hybrids inherited three 5S rDNA classes from their female parent (RCC) and only class IV from their male parent (TC). Triploid hybrids inherited class II and class III from their female parent (RCC) and class IV from their male parent (TC). Tetraploid hybrids gained class II and class III from their female parent (RCC), and generated a new 5S rDNA sequence (designated class I-N). The specific paternal 5S rDNA sequence of class V was not found in the hybrid offspring. Sequence analysis of 5S rDNA revealed the influence of hybridization and polyploidization on the organization and variation of 5S rDNA in fish. This is the first report on the coexistence in vertebrates of viable diploid, triploid and tetraploid hybrids produced by crossing parents with different chromosome numbers, and these new hybrids are novel specimens for studying the genomic variation in the first generation of interspecific hybrids, which has significance for evolution and fish genetics.

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

Aryal, P; Molloy, JA; Rivard, MJ

Purpose: To investigate the effect of plaque design and radionuclides on eye plaque dosimetry. Methods: The Monte Carlo N-particle Code version 6 (MCNP6) was used for radiation transport simulations. The 14 mm and 16 mm diameter COMS plaques and the model EP917 plaque were simulated using brachytherapy seeds containing I-125, Pd-103, and Cs-131 radionuclides. The origin was placed at the scleral inner surface. The central axis (CAX) doses of both COMS plaques at −1 mm, 0 mm, 1 mm, 2 mm, 5 mm, 10 mm, 15 mm, 20 mm, and 22.6 mm were compared to the model EP917 plaque. Dosemore » volume histograms (DVHs) were also created for both COMS plaques for the tumor and outer sclera then compared to results for the model EP917 plaque. Results: For all radionuclides, the EP917 plaque delivered higher dose (max 343%) compared to the COMS plaques, except for the 14 mm COMS plaque with Cs-131 at 1 mm and 2 mm depths from outer sclera surface. This could be due to source design. For all radionuclides, the 14 mm COMS plaque delivered higher doses compared to the 16 mm COMS plaque for the depths up to 5 mm. Dose differences were not significant beyond depths of 10 mm due to ocular lateral scatter for the different plaque designs. Tumor DVHs for the 16 mm COMS plaque with Cs-131 provided better dose homogeneity and conformity compared to other COMS plaques with I-125 and Pd-103. Using Pd-103, DVHs for the 16 mm COMS plaque delivered less dose to outer sclera compared to other plaques. Conclusion: This study identified improved tumor homogeneity upon considering radionuclides and plaque designs, and found that scleral dose with the model EP917 plaque was higher than for the 16 mm COMS plaque for all the radionuclides studied.« less

Comparison of in situ versus in vitro methods of fiber digestion at 120 and 288 hours to quantify the indigestible neutral detergent fiber fraction of corn silage samples.

PubMed

Bender, R W; Cook, D E; Combs, D K

2016-07-01

Ruminal digestion of neutral detergent fiber (NDF) is affected in part by the proportion of NDF that is indigestible (iNDF), and the rate at which the potentially digestible NDF (pdNDF) is digested. Indigestible NDF in forages is commonly determined as the NDF residue remaining after long-term in situ or in vitro incubations. Rate of pdNDF digestion can be determined by measuring the degradation of NDF in ruminal in vitro or in situ incubations at multiple time points, and fitting the change in residual pdNDF by time with log-transformed linear first order or nonlinear mathematical treatments. The estimate of indigestible fiber is important because it sets the pool size of potentially digestible fiber, which in turn affects the estimate of the proportion of potentially digestible fiber remaining in the time series analysis. Our objective was to compare estimates of iNDF based on in vitro (IV) and in situ (IS) measurements at 2 fermentation end points (120 and 288h). Further objectives were to compare the subsequent rate, lag, and estimated total-tract NDF digestibility (TTNDFD) when iNDF from each method was used with a 7 time point in vitro incubation of NDF to model fiber digestion. Thirteen corn silage samples were dried and ground through a 1-mm screen in a Wiley mill. A 2×2 factorial trial was conducted to determine the effect of time of incubation and method of iNDF analysis on iNDF concentration; the 2 factors were method of iNDF analysis (IS vs. IV) and incubation time (120 vs. 288h). Four sample replicates were used, and approximately 0.5g/sample was weighed into each Ankom F 0285 bag (Ankom Technology, Macedon, NY; pore size=25 µm) for all techniques. The IV-120 had a higher estimate of iNDF (37.8% of NDF) than IS-120 (32.1% of NDF), IV-288 (31.2% of NDF), or IS-288 technique (25.7% of NDF). Each of the estimates of iNDF was then used to calculate the rate of degradation of pdNDF from a 7 time point in vitro incubation. When the IV-120 NDF residue was used, the subsequent rates of pdNDF digestion were fastest (2.8% h(-1)) but the estimate of lag was longest (10.3h), compared with when iNDF was based on the IS-120 or IV-288 NDF residues (rates of 2.3%h(-1) and 2.4%h(-1); lag times of 9.7 and 9.8 h, respectively). Rate of pdNDF degradation was slowest (2.1% h(-1)) when IS-288 NDF residue was used as the estimate of iNDF. The estimate of lag based on IS-288 (9.4h) was similar to lag estimates calculated when IS-120 or IV-288 were used as the estimate of iNDF. The TTNDFD estimates did not differ between treatments (35.5%), however, because differences in estimated pools of iNDF resulted in subsequent changes in rates and lag times of fiber digestion that tended to cancel out. Estimates of fiber digestion kinetic parameters and TTNDFD were similar when fit to either the linear or nonlinear fiber degradation models. All techniques also yielded estimates of iNDF that were higher than predicted iNDF based on the commonly used ratio of 2.4 × lignin. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The effect of topical benzamil and amiloride on nasal potential difference in cystic fibrosis.

PubMed

Rodgers, H C; Knox, A J

1999-09-01

The electrochemical defect in the bronchial epithelium in cystic fibrosis (CF) consists of defective chloride secretion and excessive sodium reabsorption. The sodium channel blocker, amiloride, has been shown to reversibly correct the sodium reabsorption in CF subjects, but long term studies of amiloride have been disappointing due to its short duration of action. Benzamil, a benzyl substituted amiloride analogue, has a longer duration of action than amiloride in cultured human nasal epithelium. The results of the first randomized, placebo controlled, double blind, crossover study are reported here comparing the effects of benzamil and amiloride on nasal potential difference (nasal PD) in CF. Ten adults with CF attended on three occasions. At each visit baseline nasal PD was recorded, the drug (amiloride 1 x 10(-3) M, benzamil 1.7 x 10(-3) M, or 0.9% sodium chloride) was administered topically via a nasal spray, and nasal PD was measured at 15, 30 min, 1, 2, 4 and 8 h. Results were expressed as maximum change in nasal PD from baseline (PDmax), time for PDmax to return to 50% of baseline (t0.5), and the area under the curve (AUC). PDmax values for benzamil (20.6+/-0.9 mV) and amiloride (20.3+/-1.6 mV), were similar. The duration of effect was much longer for benzamil as measured as either AUC or t0.5 AUC values were 11.8+/-1.6 mV for benzamil, 2.8+/-0.4 mV for amiloride and 0.6+/-0.4 mV for placebo. The AUC value for benzamil was significantly greater than amiloride (95% confidence interval (CI) for the difference 5.3-12.7 mV, p<0.0001). t0.5 values were 4.3+/-0.7 h for benzamil and 0.6+/-0.1 h for amiloride (95% CI for the difference 2.0-5.3 h, p<0.001). It is concluded that benzamil has a similar maximal effect to amiloride but a more prolonged duration of action on nasal potential difference in cystic fibrosis. Benzamil may be a useful sodium channel blocker for the long-term treatment of the biochemical defect in the lungs of patients with cystic fibrosis.

Incremental cost-effectiveness of pharmacotherapy and two brief cognitive-behavioral therapies compared with usual care for panic disorder and noncardiac chest pain.

PubMed

Poirier-Bisson, Joannie; Marchand, André; Pelland, Marie-Eve; Lessard, Marie-Josée; Dupuis, Gilles; Fleet, Richard; Roberge, Pasquale

2013-09-01

The aim of this study was to assess the incremental cost-effectiveness ratios (ICERs) of two brief cognitive-behavioral therapy (CBT)-based interventions and a pharmacological treatment, compared with usual care, initiated in the emergency department (ED) for individuals with panic disorder (PD) with a chief complaint of noncardiac chest pain. A total of 69 patients were followed up to 6 months. The primary outcome variables were direct and indirect costs of treatment and PD severity. Panic management (PM) had an ICER of $124.05, per the Anxiety Disorders Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, severity score change (95% confidence interval [CI], $54.63-$314.57), compared with pharmacotherapy (paroxetine), with an ICER of $213.90 (95% CI, $133.51-$394.94), and brief CBT, with an ICER of $309.31 (95% CI, $151.27-$548.28). The pharmacological and CBT interventions were associated with a greater clinical improvement compared with usual care at posttest. PM presented a superior ICER, suggesting that it may be a promising treatment option to implement in EDs.

Evaluation of water-mimicking solid phantom materials for use in HDR and LDR brachytherapy dosimetry

NASA Astrophysics Data System (ADS)

Schoenfeld, Andreas A.; Thieben, Maike; Harder, Dietrich; Poppe, Björn; Chofor, Ndimofor

2017-12-01

In modern HDR or LDR brachytherapy with photon emitters, fast checks of the dose profiles generated in water or a water-equivalent phantom have to be available in the interest of patient safety. However, the commercially available brachytherapy photon sources cover a wide range of photon emission spectra, and the range of the in-phantom photon spectrum is further widened by Compton scattering, so that the achievement of water-mimicking properties of such phantoms involves high requirements on their atomic composition. In order to classify the degree of water equivalence of the numerous commercially available solid water-mimicking phantom materials and the energy ranges of their applicability, the radial profiles of the absorbed dose to water, D w, have been calculated using Monte Carlo simulations in these materials and in water phantoms of the same dimensions. This study includes the HDR therapy sources Nucletron Flexisource Co-60 HDR (60Co), Eckert und Ziegler BEBIG GmbH CSM-11 (137Cs), Implant Sciences Corporation HDR Yb-169 Source 4140 (169Yb) as well as the LDR therapy sources IsoRay Inc. Proxcelan CS-1 (131Cs), IsoAid Advantage I-125 IAI-125A (125I), and IsoAid Advantage Pd-103 IAPd-103A (103Pd). Thereby our previous comparison between phantom materials and water surrounding a Varian GammaMed Plus HDR therapy 192Ir source (Schoenfeld et al 2015) has been complemented. Simulations were performed in cylindrical phantoms consisting of either water or the materials RW1, RW3, Solid Water, HE Solid Water, Virtual Water, Plastic Water DT, Plastic Water LR, Original Plastic Water (2015), Plastic Water (1995), Blue Water, polyethylene, polystyrene and PMMA. While for 192Ir, 137Cs and 60Co most phantom materials can be regarded as water equivalent, for 169Yb the materials Plastic Water LR, Plastic Water DT and RW1 appear as water equivalent. For the low-energy sources 106Pd, 131Cs and 125I, only Plastic Water LR can be classified as water equivalent.

Evaluation of water-mimicking solid phantom materials for use in HDR and LDR brachytherapy dosimetry.

PubMed

Schoenfeld, Andreas A; Thieben, Maike; Harder, Dietrich; Poppe, Björn; Chofor, Ndimofor

2017-11-21

In modern HDR or LDR brachytherapy with photon emitters, fast checks of the dose profiles generated in water or a water-equivalent phantom have to be available in the interest of patient safety. However, the commercially available brachytherapy photon sources cover a wide range of photon emission spectra, and the range of the in-phantom photon spectrum is further widened by Compton scattering, so that the achievement of water-mimicking properties of such phantoms involves high requirements on their atomic composition. In order to classify the degree of water equivalence of the numerous commercially available solid water-mimicking phantom materials and the energy ranges of their applicability, the radial profiles of the absorbed dose to water, D w , have been calculated using Monte Carlo simulations in these materials and in water phantoms of the same dimensions. This study includes the HDR therapy sources Nucletron Flexisource Co-60 HDR ( 60 Co), Eckert und Ziegler BEBIG GmbH CSM-11 ( 137 Cs), Implant Sciences Corporation HDR Yb-169 Source 4140 ( 169 Yb) as well as the LDR therapy sources IsoRay Inc. Proxcelan CS-1 ( 131 Cs), IsoAid Advantage I-125 IAI-125A ( 125 I), and IsoAid Advantage Pd-103 IAPd-103A ( 103 Pd). Thereby our previous comparison between phantom materials and water surrounding a Varian GammaMed Plus HDR therapy 192 Ir source (Schoenfeld et al 2015) has been complemented. Simulations were performed in cylindrical phantoms consisting of either water or the materials RW1, RW3, Solid Water, HE Solid Water, Virtual Water, Plastic Water DT, Plastic Water LR, Original Plastic Water (2015), Plastic Water (1995), Blue Water, polyethylene, polystyrene and PMMA. While for 192 Ir, 137 Cs and 60 Co most phantom materials can be regarded as water equivalent, for 169 Yb the materials Plastic Water LR, Plastic Water DT and RW1 appear as water equivalent. For the low-energy sources 106 Pd, 131 Cs and 125 I, only Plastic Water LR can be classified as water equivalent.

SU-E-T-123: Anomalous Altitude Effect in Permanent Implant Brachytherapy Seeds

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

Watt, E; Spencer, DP; Meyer, T

Purpose: Permanent seed implant brachytherapy procedures require the measurement of the air kerma strength of seeds prior to implant. This is typically accomplished using a well-type ionization chamber. Previous measurements (Griffin et al., 2005; Bohm et al., 2005) of several low-energy seeds using the air-communicating HDR 1000 Plus chamber have demonstrated that the standard temperature-pressure correction factor, P{sub TP}, may overcompensate for air density changes induced by altitude variations by up to 18%. The purpose of this work is to present empirical correction factors for two clinically-used seeds (IsoAid ADVANTAGE™ {sup 103}Pd and Nucletron selectSeed {sup 125}I) for which empiricalmore » altitude correction factors do not yet exist in the literature when measured with the HDR 1000 Plus chamber. Methods: An in-house constructed pressure vessel containing the HDR 1000 Plus well chamber and a digital barometer/thermometer was pumped or evacuated, as appropriate, to a variety of pressures from 725 to 1075 mbar. Current measurements, corrected with P{sub TP}, were acquired for each seed at these pressures and normalized to the reading at ‘standard’ pressure (1013.25 mbar). Results: Measurements in this study have shown that utilization of P{sub TP} can overcompensate in the corrected current reading by up to 20% and 17% for the IsoAid Pd-103 and the Nucletron I-125 seed respectively. Compared to literature correction factors for other seed models, the correction factors in this study diverge by up to 2.6% and 3.0% for iodine (with silver) and palladium respectively, indicating the need for seed-specific factors. Conclusion: The use of seed specific altitude correction factors can reduce uncertainty in the determination of air kerma strength. The empirical correction factors determined in this work can be applied in clinical quality assurance measurements of air kerma strength for two previously unpublished seed designs (IsoAid ADVANTAGE™ {sup 103}Pd and Nucletron selectSeed {sup 125}I) with the HDR 1000 Plus well chamber.« less

Relationship between quantitative and descriptive methods of studying blood flow through intrapulmonary arteriovenous anastomoses during exercise.

PubMed

Duke, Joseph W; Elliott, Jonathan E; Laurie, Steven S; Voelkel, Thomas; Gladstone, Igor M; Fish, Mathews B; Lovering, Andrew T

2017-09-01

Several methods exist to study intrapulmonary arteriovenous anastomoses (IPAVA) in humans. Transthoracic saline contrast echocardiography (TTSCE), i.e., bubble scores, is minimally-invasive, but cannot be used to quantify the magnitude of blood flow through IPAVA (Q IPAVA ). Radiolabeled macroaggregates of albumin ( 99m Tc-MAA) have been used to quantify Q IPAVA in humans, but this requires injection of radioactive particles. Previous work has shown agreement between 99m Tc-MAA and TTSCE, but this has not been tested simultaneously in the same group of subjects. Thus, the purpose of this study was to determine if there was a relationship between Q IPAVA quantified with 99m Tc-MAA and bubble scores obtained with TTSCE. To test this, we used 99m Tc-MAA and TTSCE to quantify and detect Q IPAVA at rest and during exercise in humans. Q IPAVA significantly increased from rest to exercise using 99m Tc-MAA and TTSCE and there was a moderately-strong, but significant relationship between methods. Our data suggest that high bubble scores generally correspond with large Q IPAVA quantified with 99m Tc-MAA during exercise. Copyright © 2017 Elsevier B.V. All rights reserved.

The fusion of advanced fuels to produce medical isotopes using inertial electrostatic confinement

NASA Astrophysics Data System (ADS)

Cipiti, Benjamin B.

Experiments are described that used an Inertial Electrostatic Confinement (IEC) fusion device to create radioisotopes for medical diagnostics. The IEC concept utilizes spherically concentric electrodes to accelerate fusion ions to high energies, allowing the use of the D-D and advanced D-3He fusion reactions. The D-3He reaction produces a high-energy 14.7 MeV proton, and this proton is energetic enough to be used to create radioisotopes. This dissertation focuses first on where specifically the fusion reactions are occurring in the IEC device. It was found that at 2 mtorr operating pressures, 70% of the D-D reactions occur throughout the entire volume of the vacuum chamber. About 22% of the reactions occur in a small core in the center of the device, and the other 8% are due to embedded D-D reactions in the cathode of the device. On the other hand, for D-3He, 95% of the reactions are due to embedded reactions, and the other 5% come from a small core in the center of the device. Beam-target D-3He fusion was used to create medical isotopes in two different systems. The designs focused on creating short-lived species capable of use in Positron Emission Tomography. The first isotope created was 94mTc, a positron emitter with a 52-minute half-life. Approximately 1.5 nCi of 94mTc were created using the 94Mo(p,n) 94mTc reaction. The second isotope created was 13N, a positron emitter with a ten-minute half-life. Approximately 1.0 nCi of 13N was created using the 16O(p,alpha)13N reaction. The final part of the research investigated the effects of deuterium and helium implantation in the tungsten-rhenium cathode of the IEC device. The effect of the implantation on the surface morphology of pure tungsten was also determined using scanning electron microscopy. Deuterium did not appear to affect the surface of tungsten after high temperature (>800 C) implantation. Helium created a porous surface structure at the same temperatures starting at about 4 x 1016 ions/cm2. The pores increased in size and decreased in density with increasing temperature and fluence.

The use of {sup 99m}Tc-Al{sub 2}O{sub 3} for detection of sentinel lymph nodes in breast cancer

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

Sinilkin, I., E-mail: sinilkinig@oncology.tomsk.ru; Chernov, V.; Medvedeva, A.

2016-08-02

Purpose: to study the feasibility of using the new radiopharmaceutical based on the technetium-99m-labeled gamma-alumina for identification of sentinel lymph nodes (SLNs) in breast cancer patients. The study included two groups of breast cancer patients who underwent single photon emission computed tomography (SPECT) and intraoperaive gamma probe identification of sentinel lymph nodes (SLNs). To identify SLNs, the day before surgery Group I patients (n = 34) were injected with radioactive {sup 99m}Tc-Al{sub 2}O{sub 3}, and Group II patients (n = 30) received {sup 99m}Tc-labeled phytate colloid. A total of 37 SLNs were detected in Group I patients. The number ofmore » identified SLNs per patient ranged from 1 to 2 (the average number of identified SLNs was 1.08). Axillary lymph nodes were the most common site of SLN localization. 18 hours after {sup 99m}Tc-Al{sub 2}O{sub 3} injection, the percentage of its accumulation in the SLN was 7–11% (of the counts in the injection site) by SPECT and 17–31% by gamma probe detection. In Group II SLNs were detected in 27 patients. 18 hours after injection of the phytate colloid the percentage of its accumulation in the SLN was 1.5–2% out of the counts in the injection site by SPECT and 4–7% by gamma probe. The new radiopharmaceutical based on the {sup 99m}Tc-Al{sub 2}O{sub 3} demonstrates high accumulation in SLNs without redistribution through the entire lymphatic basin. The sensitivity and specificity of {sup 99m}Tc-Al{sub 2}O{sub 3} were 100% for both SPECT and intraoperative gamma probe identification.« less

Department of the Navy Justification of Estimates FY 1992/FY 1993 Budget Estimates Submitted to Congress February 1991, Operation and Maintenance, Navy. Book 3

DTIC Science & Technology

1991-02-01

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Evaluation of (99m)Tc-HYNIC-TMTP1 as a tumor-homing imaging agent targeting metastasis with SPECT.

PubMed

Li, Fei; Cheng, Teng; Dong, Qingjian; Wei, Rui; Zhang, Zhenzhong; Luo, Danfeng; Ma, Xiangyi; Wang, Shixuan; Gao, Qinglei; Ma, Ding; Zhu, Xiaohua; Xi, Ling

2015-03-01

TMTP1 (NVVRQ) is a novel tumor-homing peptide, which specifically targets tumor metastases, even at the early stage of occult metastasis foci. Fusing TMTP1 to therapeutic peptides or proteins can increase its anti-cancer efficacy both in vivo and in vitro. Here, we labeled TMTP1 with (99m)Tc to evaluate its targeting properties in an ovarian cancer xenograft tumor mouse model and a gastric cancer xenograft mouse model. The invasion ability of SKOV3 and highly metastatic SKOV3.ip cell lines were performed by the Transwell Invasion Assays, and then Rhodamine-TMTP1 was used to detect its affinity to these two cells. Using the co-ligand ethylenediamine-N, N'-diacetic acid (EDDA) and the bifunctional chelator 6-hydrazinonicotinic acid (HYNIC), the TMTP1 peptide was labeled with (99m)Tc. A cell-binding assay was performed by incubating cancer cells with (99m)Tc-HYNIC-TMTP1 with or without an excess dose of cold HYNIC-TMTP1. To evaluate the probe in vivo, nude mice bearing SKOV3, SKOV3.ip and MNK-45 tumor cells were established and subjected to SPECT imaging after injection with (99m)Tc-HYNIC-TMTP1. Ex vivo γ-counting of dissected tissues from the mice was used to evaluate its biodistribution. (99m)Tc-HYNIC-TMTP1 was successfully synthesized. The radiotracer also exhibited high hydrophilicity and excellent stability in vitro and in vivo. It has strong affinity to highly metastatic cancer cell lines but not to poorly metastatic cell lines. After mice were injected with (99m)Tc-HYNIC-TMTP1, non-invasive SPECT imaging detected SKOV3.ip and MNK-45 xenograft tumors but not SKOV3 xenograft tumors. This result can be inhibited by excess HYNIC-TMTP1. The uptake of (99m)Tc-HYNIC-TMTP1 in SKOV3.ip xenograft tumors was 0.182±0.017% ID/g at 2h p.i. with high renal uptake (74.32±15.05% ID/g at 2h p.i.). (99m)Tc-HYNIC-TMTP1 biodistribution and SPECT imaging demonstrated its ability to target highly metastatic tumors. Therefore, metastasis can be non-invasively investigated by SPECT imaging using (99m)Tc-HYNIC-TMTP1. Meanwhile, this radiotracer has some shortages in the low % ID/g of tumors and high accumulation in the kidney. Copyright © 2014 Elsevier Inc. All rights reserved.

MO-FG-BRA-03: A Monte-Carlo Study of Cellular Dosimetry of Radioactive Gold-Palladium Nanoparticles

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

Ma, Y; Michaud, F; Fortin, M

Purpose: Radioactive gold-palladium nanoparticles ({sup 103}Pd:Pd@Au NPs) are being developed for prostate cancer brachytherapy. Photons emitted by the radioisotope palladium (photon energy: 20.1 and 23.0 keV), interacting with gold-coating of NPs, lead to enhanced energy distribution in nucleus. Here, a simple cellular model was studied using detailed track-structure method. Methods: Geant4-DNA was used with auger electrons enabled. Biological cell was modeled as a sphere of radius r=5 µm that were immersed in a fluid containing large number of NPs at different concentrations (S=1, 2.15, 5.1, 17.2 mg-Au/g-H2O). Nucleus was modeled as a concentric sphere (r=3µm). Thickness of gold-coating on {supmore » 103}Pd core was 15nm, 20nm and 25nm, respectively. A scenario of NP diffusion was investigated, where S=5.1 mg-Au/g-H2O outside cell and S=1 mg-Au/g-H2O in cytoplasm. 10{sup 10} {sup 103}Pd decays were simulated for each combination of NP concentration and gold-coating. Results: A uniform increase in energy deposition (Edep) is observed in cell nucleus and the energy enhancement ratio (EER) is 1.16, 1.22 and 1.3 for 15nm, 20nm and 25nm of gold -coatings, respectively. Edep at the center of nucleus is increased by a factor of 1.47, 2.51 and 5.54 when the NP concentration in the cytoplasm increases from 1 mg-Au/g-H2O to 2.15, 5.10 and 17.2 mg-Au/g-H2O, respectively. When NPs diffuse into cytoplasm, the mean value of Edep in nucleus increases from 0.42 to 1.13 MeV per 10{sup 9} decays (GBq-Second) of {sup 103}Pd and the maximum value increases from 0.54 to 2.5 MeV per GBq-Second. Conclusion: These results suggest that {sup 103}Pd:Pd@Au NPs constitute a promising nanotherapeutic agent. Ongoing studies use transmission electron microscopy (TEM) images of prostate cancer.« less

Comprehensive malnutrition inflammation score as a marker of nutritional status in Chinese peritoneal dialysis patients.

PubMed

Chan, Jessie Ying Wing; Che, Kit I; Lam, Karry Mau Chu; Chow, Kai-Ming; Chung, Kwok-Yi; Li, Philip Kam-Tao; Szeto, Cheuk-Chun

2007-04-01

Malnutrition is common among peritoneal dialysis (PD) patients. However, the ideal marker of nutritional status in PD patients remained controversial. We studied 165 unselected adult PD patients. We compared the comprehensive Malnutrition-Inflammation Score (MIS) and the 7-point Subjective Global Assessment (SGA) score. The mean age was 59.2 +/- 11.5 years. Seventy patients were male. MIS significantly correlated with the SGA score (r =-0.667, P < 0.001). Of the 165 patients, 132 (80.0%) had similar classification of nutritional status by SGA and MIS (Group I); 17 (10.3%) were classified as normal by SGA but moderately malnourished by MIS (Group II), while 16 (9.7%) were classified as normal by MIS but moderately malnourished by SGA (Group III). Group II had been dialysed longer than Group I (71.7 +/- 50.3 vs 40.7 +/- 37.5 months, P = 0.011). As compared with Group I, Group III was more likely to require helper for PD exchange (37.5%vs 9.7%, P = 0.004), marginally more likely to be diabetic (62.5%vs 35.6%, P = 0.085) and had a slightly higher Charlson's comorbidity score (6.13 +/- 1.78 vs 4.98 +/- 2.1, P = 0.085), although the latter two were not statistically significant. MIS has a reasonable correlation with the conventional SGA score in PD patients. Patients with limited self-care capability, diabetes and multiple comorbidities probably had worse score (i.e. worse nutrition) revealed by SGA than by MIS, while patients who had been dialysed longer had worse score revealed by MIS than by SGA.

Possibility of high temperature superconducting phases in PdH

NASA Astrophysics Data System (ADS)

Tripodi, Paolo; Di Gioacchino, Daniele; Borelli, Rodolfo; Vinko, Jenny Darja

2003-05-01

Possible new superconducting phases with a high critical transition temperature (Tc) have been found in stable palladium-hydrogen (PdHx) samples for stoichiometric ratio x=H/Pd⩾1, in addition to the well-known low critical transition temperature (0⩽Tc⩽9) when x is in the range (0.75⩽x⩽1.00). Possible new measured superconducting phases with critical temperature in the range 51⩽Tc⩽295 K occur. This Tc varies considerably with every milli part of x when x exceeds unit. A superconducting critical current density Jc⩾6.1×104 A cm-2 has been measured at 77 K with HDC=0 T.

Synthesis and characterization of fac-Re(CO)3-aspartic-N-monoacetic acid, a structural analogue of a potential new renal tracer, fac-99mTc(CO)3(ASMA).

PubMed

Klenc, Jeffrey; Lipowska, Malgorzata; Taylor, Andrew T; Marzilli, Luigi G

2012-09-01

The reaction of an aminopolycarboxylate ligand, as partic- N - m onoacetic a cid (ASMA), with [Re(CO) 3 (H 2 O) 3 ] + was examined. The tridentate coordination of ASMA to this Re I tricarbonyl precursor yielded fac -Re(CO) 3 (ASMA) as a mixture of diastereomers. The chemistry is analogous to that of the Tc I tricarbonyl complex, which yields fac - 99m Tc(CO) 3 (ASMA) under similar conditions. The formation, structure, and isomerization of fac -Re(CO) 3 (ASMA) products were characterized by HPLC, 1 H NMR spectroscopy, and X-ray crystallography. The two major fac -Re(CO) 3 (ASMA) diastereomeric products each have a linear ONO coordination mode with two adjacent five-membered chelate rings, but they differ in the endo or exo orientation of the uncoordinated acetate group, in agreement with expectations based on previous studies. Conditions have been identified for the expedient isomerization of fac -Re(CO) 3 (ASMA) to a mixture consisting primarily of one major product. Because different isomeric species typically have different pharmacokinetic characteristics, these conditions may provide for the practical isolation of a single 99m Tc(CO) 3 (ASMA) species, thus allowing the isolation of the isomer that has optimal imaging and pharmacokinetic characteristics. This information will aid in the design of future 99m Tc radiopharmaceuticals.

Detection of atherosclerotic plaques in ApoE-deficient mice using (99m)Tc-duramycin.

PubMed

Liu, Zhonglin; Larsen, Brandon T; Lerman, Lilach O; Gray, Brian D; Barber, Christy; Hedayat, Ahmad F; Zhao, Ming; Furenlid, Lars R; Pak, Koon Y; Woolfenden, James M

2016-08-01

Apoptosis of macrophages and smooth muscle cells is linked to atherosclerotic plaque destabilization. The apoptotic cascade leads to exposure of phosphatidylethanolamine (PE) on the outer leaflet of the cell membrane, thereby making apoptosis detectable using probes targeting PE. The objective of this study was to exploit capabilities of a PE-specific imaging probe, (99m)Tc-duramycin, in localizing atherosclerotic plaque and assessing plaque evolution in apolipoprotein-E knockout (ApoE(-/-)) mice. Atherosclerosis was induced in ApoE(-/-) mice by feeding an atherogenic diet. (99m)Tc-duramycin images were acquired using a small-animal SPECT imager. Six ApoE(-/-) mice at 20weeks of age (Group I) were imaged and then sacrificed for ex vivo analyses. Six additional ApoE(-/-) mice (Group II) were imaged at 20 and 40weeks of age before sacrifice. Six ApoE wild-type (ApoE(+/+)) mice (Group III) were imaged at 40weeks as controls. Five additional ApoE(-/-) mice (40weeks of age) (Group IV) were imaged with a (99m)Tc-labeled inactive peptide, (99m)Tc-LinDUR, to assess (99m)Tc-duramycin targeting specificity. Focal (99m)Tc-duramycin uptake in the ascending aorta and aortic arch was detected at 20 and 40weeks in the ApoE(-/-) mice but not in ApoE(+/+) mice. (99m)Tc-duramycin uptake in the aortic lesions increased 2.2-fold on quantitative imaging in the ApoE(-/-) mice between 20 and 40weeks. Autoradiographic and histological data indicated significantly increased (99m)Tc-duramycin uptake in the ascending aorta and aortic arch associated with advanced plaques. Quantitative autoradiography showed that the ratio of activity in the aortic arch to descending thoracic aorta, which had no plaques or radioactive uptake, was 2.1 times higher at 40weeks than at 20weeks (6.62±0.89 vs. 3.18±0.29, P<0.01). There was barely detectable focal uptake of (99m)Tc-duramycin in the aortic arch of ApoE(+/+) mice. No detectable (99m)Tc-LinDUR uptake was observed in the aortas of ApoE(-/-) mice. PE-targeting properties of (99m)Tc-duramycin in the atherosclerotic mouse aortas were noninvasively characterized. (99m)Tc-duramycin is promising in localizing advanced atherosclerotic plaques. Copyright © 2016 Elsevier Inc. All rights reserved.

Organ distribution of technetium-99m-labeled Corynebacterium parvum in normal and tumor-bearing mice

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

Barth, R.F.; Singla, O.

1978-01-01

The distribution patterns were studied for /sup 99m/Tc-labeled Corynebacterium parvum in normal and tumor-bearing mice. C57BL/6 mice were given i.v., i.p., or s.c. injections of 250 ..mu..g of /sup 99m/Tc-labeled C. parvum and killed at 10 min, 1, 4, and 24 hr. After iv. administration, labeled organisms were distributed primarily to the liver, the lungs, and the blood (46% of injected dose), followed by the gastrointestinal tract, the spleen, and the kidneys (11%). Total recoverable radioactivity, which was defined as the percentage of injected dose that was recovered, ranged from 59% at 10 min to 15% at 24 hr. Inmore » contrast to this, /sup 99m/TcS colloid, an inert particulate material, was localized almost entirely in the liver, and the amount recoverable remained constant over 24 hr. One hr after i.p. administration of /sup 99m/Tc-labeled C. parvum, the gastrointestinal tract accounted for 27% of the injected radioactivity, followed by liver, blood, and spleen (12%). This was rapidly excreted between 4 and 24 hr, at which time only 12% of the injected dose was recovered. The skin accounted for 54.6% of the injected radioactivity 1 hr after s.c. injection, 6% 4 hr after s.c. injection, and 0.8% at 24 hr after s.c. injection.« less

Tuning the Curie temperature of FeCo compounds by tetragonal distortion

NASA Astrophysics Data System (ADS)

Jakobsson, A.; Şaşıoǧlu, E.; Mavropoulos, Ph.; Ležaić, M.; Sanyal, B.; Bihlmayer, G.; Blügel, S.

2013-09-01

Combining density-functional theory calculations with a classical Monte Carlo method, we show that for B2-type FeCo compounds, tetragonal distortion gives rise to a strong reduction of the Curie temperature TC. The TC monotonically decreases from 1575 K (for c /a=1) to 940 K (for c /a=√2 ). We find that the nearest neighbor Fe-Co exchange interaction is sufficient to explain the c/a behavior of the TC. Combination of high magnetocrystalline anisotropy energy with a moderate TC value suggests tetragonal FeCo grown on the Rh substrate with c /a=1.24 to be a promising material for heat-assisted magnetic recording applications.

In Vitro Evolution of the Human Immunodeficiency Virus Type 1 Gag-Protease Region and Maintenance of Reverse Transcriptase Resistance following Prolonged Drug Exposure†

PubMed Central

La Seta Catamancio, Simona; De Pasquale, Maria Pia; Citterio, Paola; Kurtagic, Semir; Galli, Massimo; Rusconi, Stefano

2001-01-01

We studied the human immunodeficiency virus type 1 phenotypic and genotypic profiles of a dual drug-resistant isolate (isolate 14aPost-DR) selected for zidovudine (ZDV) and lamivudine (3TC) resistance and then cultured in the presence of 3TC and a protease inhibitor: indinavir (IDV), ritonavir, or KNI-272. The IDV-treated virus was highly resistant to 3TC, ZDV, and IDV and accumulated protease mutations at positions M46I and V82F. A change from alanine to valine was observed in 4 of 10 clones in the P2 position of the p7-p1 Gag-protease cleavage site, linked to position M46I in the dominant viral quasispecies. Previous 3TC resistance did not impair the development of additional mutations in the protease and Gag-protease cleavage regions. PMID:11230439

Effect of electric arc, gas oxygen torch and induction melting techniques on the marginal accuracy of cast base-metal and noble metal-ceramic crowns.

PubMed

Gómez-Cogolludo, Pablo; Castillo-Oyagüe, Raquel; Lynch, Christopher D; Suárez-García, María-Jesús

2013-09-01

The aim of this study was to identify the most appropriate alloy composition and melting technique by evaluating the marginal accuracy of cast metal-ceramic crowns. Seventy standardised stainless-steel abutments were prepared to receive metal-ceramic crowns and were randomly divided into four alloy groups: Group 1: palladium-gold (Pd-Au), Group 2: nickel-chromium-titanium (Ni-Cr-Ti), Group 3: nickel-chromium (Ni-Cr) and Group 4: titanium (Ti). Groups 1, 2 and 3 were in turn subdivided to be melted and cast using: (a) gas oxygen torch and centrifugal casting machine (TC) or (b) induction and centrifugal casting machine (IC). Group 4 was melted and cast using electric arc and vacuum/pressure machine (EV). All of the metal-ceramic crowns were luted with glass-ionomer cement. The marginal fit was measured under an optical microscope before and after cementation using image analysis software. All data was subjected to two-way analysis of variance (ANOVA). Duncan's multiple range test was run for post-hoc comparisons. The Student's t-test was used to investigate the influence of cementation (α=0.05). Uncemented Pd-Au/TC samples achieved the best marginal adaptation, while the worst fit corresponded to the luted Ti/EV crowns. Pd-Au/TC, Ni-Cr and Ti restorations demonstrated significantly increased misfit after cementation. The Ni-Cr-Ti alloy was the most predictable in terms of differences in misfit when either torch or induction was applied before or after cementation. Cemented titanium crowns exceeded the clinically acceptable limit of 120μm. The combination of alloy composition, melting technique, casting method and luting process influences the vertical seal of cast metal-ceramic crowns. An accurate use of the gas oxygen torch may overcome the results attained with the induction system concerning the marginal adaptation of fixed dental prostheses. Copyright © 2013 Elsevier Ltd. All rights reserved.

Using Smartphones and Machine Learning to Quantify Parkinson Disease Severity: The Mobile Parkinson Disease Score.

PubMed

Zhan, Andong; Mohan, Srihari; Tarolli, Christopher; Schneider, Ruth B; Adams, Jamie L; Sharma, Saloni; Elson, Molly J; Spear, Kelsey L; Glidden, Alistair M; Little, Max A; Terzis, Andreas; Dorsey, E Ray; Saria, Suchi

2018-03-26

Current Parkinson disease (PD) measures are subjective, rater-dependent, and assessed in clinic. Smartphones can measure PD features, yet no smartphone-derived rating score exists to assess motor symptom severity in real-world settings. To develop an objective measure of PD severity and test construct validity by evaluating the ability of the measure to capture intraday symptom fluctuations, correlate with current standard PD outcome measures, and respond to dopaminergic therapy. This observational study assessed individuals with PD who remotely completed 5 tasks (voice, finger tapping, gait, balance, and reaction time) on the smartphone application. We used a novel machine-learning-based approach to generate a mobile Parkinson disease score (mPDS) that objectively weighs features derived from each smartphone activity (eg, stride length from the gait activity) and is scaled from 0 to 100 (where higher scores indicate greater severity). Individuals with and without PD additionally completed standard in-person assessments of PD with smartphone assessments during a period of 6 months. Ability of the mPDS to detect intraday symptom fluctuations, the correlation between the mPDS and standard measures, and the ability of the mPDS to respond to dopaminergic medication. The mPDS was derived from 6148 smartphone activity assessments from 129 individuals (mean [SD] age, 58.7 [8.6] years; 56 [43.4%] women). Gait features contributed most to the total mPDS (33.4%). In addition, 23 individuals with PD (mean [SD] age, 64.6 [11.5] years; 11 [48%] women) and 17 without PD (mean [SD] age 54.2 [16.5] years; 12 [71%] women) completed in-clinic assessments. The mPDS detected symptom fluctuations with a mean (SD) intraday change of 13.9 (10.3) points on a scale of 0 to 100. The measure correlated well with the Movement Disorder Society Unified Parkinson Disease's Rating Scale total (r = 0.81; P < .001) and part III only (r = 0.88; P < .001), the Timed Up and Go assessment (r = 0.72; P = .002), and the Hoehn and Yahr stage (r = 0.91; P < .001). The mPDS improved by a mean (SD) of 16.3 (5.6) points in response to dopaminergic therapy. Using a novel machine-learning approach, we created and demonstrated construct validity of an objective PD severity score derived from smartphone assessments. This score complements standard PD measures by providing frequent, objective, real-world assessments that could enhance clinical care and evaluation of novel therapeutics.

Novel mixed ligand technetium complexes as 5-HT1A receptor imaging agents.

PubMed

León, A; Rey, A; Mallo, L; Pirmettis, I; Papadopoulos, M; León, E; Pagano, M; Manta, E; Incerti, M; Raptopoulou, C; Terzis, A; Chiotellis, E

2002-02-01

The synthesis, characterization and biological evaluation of two novel 3 + 1 mixed ligand 99mTc-complexes, bearing the 1-(2-methoxyphenylpiperazine) moiety, a fragment of the true 5-HT1A antagonist WAY 100635, is reported. Complexes at tracer level 99mTcO[(CH3CH2)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N(CH2CH2)2NCH2CH2S], 99mTc-1, and 99mTcO[((CH3)2CH)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N (CH2CH2)2NCH2CH2S], 99mTc-2, were prepared using 99mTc-glucoheptonate as precursor. For structural characterization, the analogous oxorhenium complexes, Re-1 and Re-2, were prepared by ligand exchange reaction using ReOCl3(PPh3)2 as precursor, and characterized by elemental analysis and spectroscopic methods. Complex Re-1 was further characterized by crystallographic analysis. Labeling was performed with high yield (>85%) and radiochemical purity (>90%) using very low ligand concentration. The structure of 99mTc complexes was established by comparative HPLC using the well-characterized oxorhenium analogues as references. In vitro binding assays demonstrated the affinity of these complexes for 5-HT1A receptors (IC50 : 67 and 45 nM for Re-1 and Re-2 respectively). Biological studies in mice showed the ability of 99mTc-1 and 99mTc-2 complexes to cross the intact blood-brain barrier (1.4 and 0.9% dose/g, respectively at 1 min post-inj.). The distribution of these complexes in various regions in rat brain is inhomogeneous. The highest ratio between areas reach and poor in 5-HT1A receptors was calculated for complex Tc-1 at 60 min p.i. (hippocampus/cerebellum = 1.7).

Influence of skin colour on diagnostic accuracy of the jaundice meter JM 103 in newborns.

PubMed

Samiee-Zafarghandy, S; Feberova, J; Williams, K; Yasseen, A S; Perkins, S L; Lemyre, B

2014-11-01

To assess the diagnostic accuracy of the JM 103 as a screening tool for neonatal jaundice and explore differential effects based on skin colour. We prospectively compared the transcutaneous bilirubin (TcB) and serum bilirubin (TSB) measurements of newborns over a 3 month-period. Skin colour was assigned via reference colour swatches. Diagnostic measures of the TcB/TSB comparison were made and clinically relevant TcB cut-off values were determined for each skin colour group. 451 infants (51 light, 326 medium and 74 dark skin colour) were recruited. The association between TcB and TSB was high for all skin colours (rs>0.9). The Bland-Altman analysis showed an absolute mean difference between the two measures of 13.3±26.4 µmol/L with broad limits of agreement (-39.4-66.0 µmol/L), with TcB underestimating TSB in light and medium skin colours and overestimating in dark skin colour. Diagnostic measures were also consistently high across skin colours, with no clinically significant differences observed. The JM 103 is a useful screening tool to identify infants in need of serum bilirubin, regardless of skin colour. The effect of skin colour on the accuracy of this device at high levels of serum bilirubin could not be assessed fully due to small numbers in the light and dark groups. 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.

Assessing activation of hepatic stellate cells by (99m)Tc-3PRGD2 scintigraphy targeting integrin αvβ3: a feasibility study.

PubMed

Zhang, Xin; Xin, Jun; Shi, Yu; Xu, Weina; Yu, Shupeng; Yang, Zhiguang; Liu, Changping; Cao, Li; Guo, Qiyong

2015-03-01

Hepatic stellate cell (HSC) activation, which is accompanied by increased expression of integrin αvβ3, is an important factor in liver fibrogenesis. Molecular imaging targeting the integrin αvβ3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvβ3 on the activated HSCs (aHSCs) in the injured liver, and then provide important prognostic information. (99m)Tc-3PRGD2 is such a radiotracer specific for integrin αvβ3. In this study, we aimed to compare the differences in liver uptake and retention of the (99m)Tc-3PRGD2 between normal liver and injured liver to evaluate the feasibility of (99m)Tc-3PRGD2 scintigraphy for this purpose. We used planar scintigraphy to assess changes in integrin αvβ3 binding of intravenously-administered (99m)Tc-3PRGD2 in the livers of rats with thioacetamide (TAA)-induced liver fibrosis compared with the controls. We co-injected cold c(RGDyK) with (99m)Tc-3PRGD2 to assess the specific binding of the radiotracer. We performed Sirius red staining to assess liver fibrosis, immunofluorescent colocalization to identify the location of integrin αvβ3 expressed in the fibrotic liver, and we measured protein and messenger RNA expression of integrin αvβ3 and alpha smooth muscle actin (α-SMA) in the control and fibrotic livers. The fibrotic livers showed enhanced (99m)Tc-3PRGD2 uptake and retention. The radiotracer was demonstrated to bind specifically with the integrin αvβ3 mainly expressed on the aHSCs. The liver-to-heart ratio at 30 min post-injection was higher in the fibrotic livers than in the control livers (TAA, 1.98±0.08 vs. control, 1.50±0.12, p<0.01). The liver t1/2 was longer than in the controls (TAA, 27.07±10.69 min vs. control, 12.67±4.10 min, p<0.01). The difference of heart t1/2 between the two groups was not statistically significant (TAA, 3.13±0.63 min vs. control, 3.41±0.77 min, p=0.94). (99m)Tc-3PRGD2 molecular imaging can provide a non-invasive method for assessing activation of HSCs. Copyright © 2014 Elsevier Inc. All rights reserved.

ROLE OF TUNGSTEN IN THE AQUEOUS PHASE HYDRODEOXYGENATION OF ETHYLENE GLYCOL ON TUNGSTATED ZIRCONIA SUPPORTED PALLADIUM

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

Marin-Flores, Oscar G.; Karim, Ayman M.; Wang, Yong

2014-11-15

The focus of the present work was specifically on the elucidation of the role played by tungsten on the catalytic activity and selectivity of tungstated zirconia supported palladium (Pd-mWZ) for the aqueous phase hydrodeoxygenation (APHDO) of ethylene glycol (EG). Zirconia supported palladium (Pd-mZ) was used as reference. The catalysts were prepared via incipient wet impregnation and characterized using X-ray diffraction (XRD), temperature-programmed reduction (TPR), CO pulse chemisorption, CO-DRIFTS, ammonia temperature-programmed desorption (NH3-TPD) and pyridine adsorption. The presence of W results in larger Pd particles on supported Pd catalysts, i.e., 0.9 and 6.1 nm Pd particles are for Pd-mZ and Pd-mWZ,more » respectively. For comparison purposes, the activity of the catalytic materials used in this work was obtained using a well-defined set of operating conditions. The catalytic activity measurements show that the overall intrinsic activity of Pd particles on mWZ is 1.9 times higher than on mZ. APHDO process appears to be highly favored on Pd-mWZ whereas Pd-mZ exhibits a higher selectivity for reforming. This difference in terms of selectivity seems to be related to the high concentration of Brønsted acid sites and electron-deficient Pd species present on Pd-mWZ.« less

Protective effect of tangeritin in transgenic Drosophila model of Parkinson's disease.

PubMed

Fatima, Ambreen; Khanam, Saba; Rahul, Rahul; Jyoti, Smita; Naz, Falaq; Ali, Fahad; Siddique, Yasir Hasan

2017-01-01

Parkinson's disease (PD) is a neurodegenerative disorder caused due to the loss of dopaminergic neurons in substantia nigra region of midbrain. The disease is characterized by the accumulation of alpha-synuclein into depositions known as lewy bodies. Till date there is no cure for PD but the limited number of medications may provide temporary relief from the PD symptoms. Flavonoids are a group of polyphenols found in plants. The health benefits of flavonoids have been universally accepted. Tangeritin is a pentamethoxy flavone found in the peels of Mandarin oranges ( Citrus reticulata ). The present study was conducted to study the effect of tangeritin on the symptoms of PD exhibited by the PD model transgenic flies ( Drosophila melanogaster) . Tangeritin at a final concentration of 5, 10 and 20 microM was added to the diet and the flies were allowed to feed on it for 24 days. At the same time other set of PD flies were allowed to feed on a diet having 10-3 M of L-Dopa. The effect of tangeritin was studied on the activity pattern, climbing ability, dopamine content, oxidative stress markers (lipid peroxidation, reduced glutathione, glutathione-S-transferase, protein carbonyl content and monoamine oxidase activity) and on the histopathology of the brain of PD model flies. The study showed that the exposure of PD flies to different doses of tangeritin showed a marked delay in the loss of climbing ability and increase in the dopamine content. Tangeritin also showed a reduction in various oxidative stress markers. Hence it is concluded that tangeritin showed a marked reduction in the PD symptoms and thus could be of great importance for further research in treating PD.

THERMODYNAMIC PROPERTIES OF Zr AND Hf HALIDES (in Rumanian)

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

Lungu, S.N.

1962-01-01

The following standard heats of formation were found: ZrCl/sub 3/, 178.6 plus or minus 3.2; ZrCl/sub 2/, 124.3 plus or minus 3; ZrBr/sub 3/, 151 plus or minus 7; Zr Br/sbu 2/, 100 plus or minus 6; ZrI/sub 3/, 103 plus or minus 6; ZrI/sub 2/, 68 plus or minus 4; and HfCl/sub 4/, 239.4 plus or minus 5.5; HfCl/sub 3/, 186.6; HfCl/sub 2/, 130; HfBr/sub 4/, 200; HfBr/sub 3/, 157; HfBr / sub 2/, 108; HfI/sub 4/, 140; HfI/sub 3/, 113; and HfI/sub 2/, 72 kcal/mole. (R.V.J.)

SU-E-T-212: Comparison of TG-43 Dosimetric Parameters of Low and High Energy Brachytherapy Sources Obtained by MCNP Code Versions of 4C, X and 5

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

Zehtabian, M; Zaker, N; Sina, S

2015-06-15

Purpose: Different versions of MCNP code are widely used for dosimetry purposes. The purpose of this study is to compare different versions of the MCNP codes in dosimetric evaluation of different brachytherapy sources. Methods: The TG-43 parameters such as dose rate constant, radial dose function, and anisotropy function of different brachytherapy sources, i.e. Pd-103, I-125, Ir-192, and Cs-137 were calculated in water phantom. The results obtained by three versions of Monte Carlo codes (MCNP4C, MCNPX, MCNP5) were compared for low and high energy brachytherapy sources. Then the cross section library of MCNP4C code was changed to ENDF/B-VI release 8 whichmore » is used in MCNP5 and MCNPX codes. Finally, the TG-43 parameters obtained using the MCNP4C-revised code, were compared with other codes. Results: The results of these investigations indicate that for high energy sources, the differences in TG-43 parameters between the codes are less than 1% for Ir-192 and less than 0.5% for Cs-137. However for low energy sources like I-125 and Pd-103, large discrepancies are observed in the g(r) values obtained by MCNP4C and the two other codes. The differences between g(r) values calculated using MCNP4C and MCNP5 at the distance of 6cm were found to be about 17% and 28% for I-125 and Pd-103 respectively. The results obtained with MCNP4C-revised and MCNPX were similar. However, the maximum difference between the results obtained with the MCNP5 and MCNP4C-revised codes was 2% at 6cm. Conclusion: The results indicate that using MCNP4C code for dosimetry of low energy brachytherapy sources can cause large errors in the results. Therefore it is recommended not to use this code for low energy sources, unless its cross section library is changed. Since the results obtained with MCNP4C-revised and MCNPX were similar, it is concluded that the difference between MCNP4C and MCNPX is their cross section libraries.« less

Experimental Infection of Horses with an Attenuated Venezuelan Equine Encephalomyelitis Vaccine (Strain TC-83)

PubMed Central

Walton, Thomas E.; Alvarez, Otto; Buckwalter, Ross M.; Johnson, Karl M.

1972-01-01

Ten horses (Equus caballus) were vaccinated with strain TC-83 Venezuelan equine encephalomyelitis (VEE) virus vaccine. Febrile responses and leukopenia due to a reduction of lymphocytes and neutrophils were observed in all animals. Viremias were demonstrable in eight horses, with a maximum of 103.5 median tissue culture infectious dose units per ml of serum in two horses. Clinical illness with depression and anorexia were observed in five horses. Neutralizing (N), hemagglutination-inhibiting, and complement-fixing antibodies to the vaccine virus were demonstrable by 5, 6.5, and 7 days, respectively, after vaccination. Differential titrations of serum to six VEE strains revealed high titers of N antibody to vaccine virus, moderate titers to the epizootic Trinidad donkey no. 1 strain (VEE antigenic subtype I, variant A) from which TC-83 was derived, and low titers to two other epizootic strains (subtype I, variants B and C) in all horses at 1 month after vaccination; some animals responded with low levels of N antibody to the enzootic viruses (subtype I, variants D and E). Fourteen months after vaccination, six animals with detectable N antibody were challenged with MF-8 (subtype I, variant B), an epidemic-epizootic strain isolated in 1969 from a man in Honduras. All horses resisted challenge with the equine pathogenic strain of VEE. Marked increases of N antibody in most horses were demonstrable to some VEE strains when tested 1 month after challenge. PMID:4637604

Characterization of Non-pertechnetate Species Relevant to the Hanford Tank Waste

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

Chatterjee, Sayandev; Andersen, Amity; Du, Yingge

Among radioactive constituents present in the tank waste stored at the U.S. DOE Hanford Site, technetium-99 (Tc), which is generated from the fission of 235U and 239Pu in high yields, presents a unique challenge in that it has a long half-life ( = 292 keV; T1/2 = 2.11105 y) and exists predominately in soluble forms in the liquid supernatant and salt cake fractions of the waste. In the strongly alkaline environments prevalent in most of the tank waste, its dominant chemical form is pertechnetate (TcO 4 -, oxidation state +7). However, attempts to remove Tc from the Hanford tank wastemore » using ion-exchange processes specific to TcO 4 - only met with limited success, particularly when processing tank waste samples containing elevated concentrations of organic complexants. This suggests that a significant fraction of the soluble Tc can be present as low-valent Tc (oxidation state < +7) (non-pertechnetate). The chemical identities of these non-pertechnetate species are poorly understood. Previous analysis of the SY-101 and SY-103 tank waste samples provided strong evidence that non-pertechnetate can be comprised of [fac-Tc(CO) 3] + complexes containing Tc in oxidation state +1 (Lukens et al. 2004). During the last three years, our team has expanded this work and demonstrated that high-ionic-strength solutions typifying tank waste supernatants promote oxidative stability of the [fac-Tc(CO) 3] + species (Rapko et al. 2013a; 2013b; Levitskaia et al. 2014; Chatterjee et al. 2015). Obtained results also suggest possible stabilization of Tc(VI) and potentially Tc(IV) oxidation states in the high-ionic-strength alkaline matrices particularly in the presence of organic chelators, so that Tc(IV, VI) can serve as important redox intermediates facilitating the reduction of Tc(VII) to Tc(I). Designing strategies for effective Tc management, including separation and immobilization, necessitates understanding the molecular structure of the non-pertechnetate species and their identification in the actual tank waste samples, which would facilitate development of new treatment technologies effective for dissimilar Tc species. The key FY 2016 results are summarized below.« less

Is the Image Quality of I-124-PET Impaired by an Automatic Correction of Prompt Gammas?

PubMed Central

Preylowski, Veronika; Schlögl, Susanne; Schoenahl, Frédéric; Jörg, Gerhard; Samnick, Samuel; Buck, Andreas K.; Lassmann, Michael

2013-01-01

Objectives The aim of this study is to evaluate the quality of I-124 PET images with and without prompt gamma compensation (PGC) by comparing the recovery coefficients (RC), the signal to noise ratios (SNR) and the contrast to F-18 and Ga-68. Furthermore, the influence of the PGC on the quantification and image quality is evaluated. Methods For measuring the image quality the NEMA NU2-2001 PET/SPECT-Phantom was used containing 6 spheres with a diameter between 10 mm and 37 mm placed in water with different levels of background activity. Each sphere was filled with the same activity concentration measured by an independently cross-calibrated dose calibrator. The “hot” sources were acquired with a full 3D PET/CT (Biograph mCT®, Siemens Medical USA). Acquisition times were 2 min for F-18 and Ga-68, and 10 min for I-124. For reconstruction an OSEM algorithm was applied. For I-124 the images were reconstructed with and without PGC. For the calculation of the RCs the activity concentrations in each sphere were determined; in addition, the influence of the background correction was studied. Results The RCs of Ga-68 are the smallest (79%). I-124 reaches similar RCs (87% with PGC, 84% without PGC) as F-18 (84%). showing that the quantification of I-124 images is similar to F-18 and slightly better than Ga-68. With background activity the contrast of the I-124 PGC images is similar to Ga-68 and F-18 scans. There was lower background activity in the I-124 images without PGC, which probably originates from an overcorrection of the scatter contribution. Consequently, the contrast without PGC was much higher than with PGC. As a consequence PGC should be used for I-124. Conclusions For I-124 there is only a slight influence on the quantification depending on the use of the PGC. However, there are considerable differences with respect to I-124 image quality. PMID:24014105

Driving safety in Parkinson's disease.

PubMed

Zesiewicz, T A; Cimino, C R; Malek, A R; Gardner, N; Leaverton, P L; Dunne, P B; Hauser, R A

2002-12-10

In this study, 39 patients with PD and 25 control subjects without neurologic disease completed testing in a driving simulator. PD patients had more total collisions on the driving simulator than control subjects (t = -3.7, p < 0.01). In PD patients, collisions were associated with Hoehn and Yahr stage (chi(2) = 12.4, p = 0.006) and correlated with Unified Parkinson's Disease Rating Scale score (r = 0.5, p < 0.01).

Biological and Molecular Characterization of Trypanosoma cruzi Strains from Four States of Brazil.

PubMed

Ribeiro, Aline Rimoldi; Lima, Luciana; de Almeida, Larissa Aguiar; Monteiro, Joana; Moreno, Cláudia Jassica Gonçalves; Nascimento, Juliana Damieli; de Araújo, Renato Freitas; Mello, Fernanda; Martins, Luciamáre Perinetti Alves; Graminha, Márcia Aparecida Silva; Teixeira, Marta Maria Geraldes; Silva, Marcelo Sousa; Steindel, Mário; da Rosa, João Aristeu

2018-02-01

Chagas disease affects between six and seven million people. Its etiological agent, Trypanosoma cruzi , is classified into six discrete typing units (DTUs). The biological study of 11 T. cruzi strains presented here included four parameters: growth kinetics, parasitemia curves, rate of macrophage infection, and serology to evaluate IgM, total IgG, IgG1, IgG2a, and IgG3. Sequencing of small subunit of ribosomal RNA (SSU rRNA)was performed and the T. cruzi strains were classified into three DTUs. When their growth in liver infusion tryptose medium was represented in curves, differences among the strains could be noted. The parasitemia profile varied among the strains from the TcI, TcII, and TcIII groups, and the 11 T. cruzi strains produced distinct parasitemia levels in infected BALB/c. The TcI group presented the highest rate of macrophage infection by amastigotes, followed by TcII and TcIII. Reactivity to immunoglobulins was observed in the TcI, TcII, and TcIII; all the animals infected with the different strains of T. cruzi showed anti- T. cruzi antibodies. The molecular study presented here resulted in the classification of the T. cruzi strains into the TcI (Bolivia, T lenti, Tm, SC90); TcII (Famema, SC96, SI8, Y); and TcIII (QMM3, QMM5, SI5) groups. These biological and molecular results from 11 T. cruzi strains clarified the factors involved in the biology of the parasite and its hosts. The collection of triatomine (vector) species, and the study of geographic distribution, as well as biological and molecular characterization of the parasite, will contribute to the reporting and surveillance measures in Brazilian states.

Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 2: discovery of novel [1,2,4]Triazolo[1,5-a]pyrimidines using a structure-guided core-refining approach.

PubMed

Wang, Liu; Tian, Ye; Chen, Wenmin; Liu, Hong; Zhan, Peng; Li, Dongyue; Liu, Huiqing; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong

2014-10-06

Guided by crystal structures of HIV-1 RT/DAPY complex and molecular modeling studies, a series of novel [1,2,4]triazolo[1,5-a]pyrimidine derivatives were rationally designed via structure-based core refining approach, synthesized through the readily accessible synthetic methods and evaluated for their anti-HIV activities in MT-4 cells. Preliminary biological evaluation indicated that most of the compounds exhibited marked inhibitory activity against the wild-type HIV-1 IIIB. Particularly, compound 7n was the most potent inhibitor against wild-type and K103N/Y181C double resistant mutant strain of HIV-1, possessing EC50 values of 0.02 μM and 7.6 μM, respectively, which were much better than or similar to nevirapine (NVP, EC50 = 0.15 μM, 2.9 μM) and delavirdine (DLV, EC50 = 0.07 μM, >36 μM). Besides, some other compounds, 5b, 7c, 7e, 7f, and 7m, were also endowed with favorable anti-HIV-1 potency (EC50 = 0.07, 0.05, 0.05, 0.07, and 0.05 μM, respectively), which were better than or similar to those of NVP and DLV, suggesting a high potential to further develop this type of bridgehead nitrogen heterocycle as a novel class of NNRTIs with improved antiviral efficacy and resistance profile. The selected compound, 7i, was found moderately inhibitory towards RT (IC50 = 0.39 μM), which was higher than for ETV (IC50 = 0.56 μM). Preliminary structure-activity relationships (SARs) and molecular modeling of these new analogues were detailed in this manuscript. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Sex steroid modulation of cortisol secretion in sheep.

PubMed

van Lier, E; Carriquiry, M; Meikle, A

2014-06-01

There is strong evidence that the gonads modulate the hypothalamic-pituitary-adrenal axis. To investigate these sex differences at the adrenal glands of sheep we compared the cortisol response to ACTH (experiment 1) and measured the relative expression of oestrogen receptor alpha (ERS1), androgen receptor (AR), melanocortin 2 receptor (MC2R) and steroid acute regulatory protein (STAR) mRNA in adrenal glands (experiment 2) of gonadectomised rams and ewes either with or without sex steroid replacement. In experiment 1 six castrated adult rams and four ovariectomised adult ewes were used in two ACTH trials. On each trial blood samples were taken every 15 min for 4 h through an indwelling jugular catheter and each animal received 0.5 mg of an ACTH analogue i.v., immediately after the sample at 1 h from the beginning of the trial. Four days after the first trial the males received 100 mg of Testosterone Cyclopentilpropionate (TC) i.m. and the females received 2.5 mg of Oestradiol Benzoate (EB) i.m. At 72 h after TC or EB administration the second trial was performed. In experiment 2 the adrenal glands were obtained from gonadectomised adult rams (n=8) and adult ewes (n=8). Four rams received 100 mg of TC i.m. and four females received 0.5 mg of EB i.m. Blood samples were taken at 0, 12, 24, 48 and 72 h relative to steroid replacement and the animals were thereafter slaughtered. Cortisol, testosterone and 17β-oestradiol were determined by radioimmunoanalysis. The transcripts of ERS1, AR, MC2R and STAR were determined by real-time reverse transcription PCR in adrenal tissue. Cortisol secretion was higher in female sheep than in male sheep, and higher in EB-treated than non-treated ewes. No difference in cortisol secretion was observed between TC-treated and non-treated rams. Gonadectomised rams treated with TC presented greater AR mRNA and MC2R mRNA expression than males without the steroid replacement. Gonadectomised ewes treated with EB tended to present lower AR mRNA than the ones without steroid replacement. Gonadectomised rams with TC also had greater AR mRNA, ERS1 mRNA and MC2R mRNA expression than ewes treated with EB. The relative amount of STAR transcript was not different among the different groups. The results confirm sex differences in ACTH-induced cortisol secretion in sheep, as well as in the expression of the receptor proteins for both 17β-oestradiol and testosterone in the sheep adrenal gland. However, the underlying mechanisms for sex steroid modulation remain unresolved.

Evaluation of 99mTc-MIBI in thyroid gland imaging for the diagnosis of amiodarone-induced thyrotoxicosis

PubMed Central

Zhang, Ruiguo

2017-01-01

Objective: Amiodarone-induced thyrotoxicosis (AIT) is caused by amiodarone as a side effect of cardiovascular disease treatment. Based on the differences in their pathological and physiological mechanisms, many methods have been developed so far to differentiate AIT subtypes such as colour flow Doppler sonography (CFDS) and 24-h radioiodine uptake (RAIU). However, these methods suffer from inadequate accuracy in distinguishing different types of AITs and sometimes lead to misdiagnosis and delayed treatments. Therefore, there is an unmet demand for an efficient method for accurate classification of AIT. Methods: Technetium-99 methoxyisobutylisonitrile (99mTc-MIBI) thyroid imaging was performed on 15 patients for AIT classification, and the results were compared with other conventional methods such as CFDS, RAIU and 99mTcO4 imaging. Results: High uptake and retention of MIBI in thyroid tissue is characteristic in Type I AIT, while in sharp contrast, low uptake of MIBI in the thyroid tissue was observed in Type II AIT. Mixed-type AIT shows uptake value between Types I and II. MIBI imaging outperforms other methods with a lower misdiagnosis rate. Conclusion: Among the methods evaluated, MIBI imaging enables an accurate identification of Type I, II and mixed-type AITs by showing distinct images for different types of AITs. The results obtained from our selected subjects revealed that MIBI imaging is a reliable method for diagnosis and classification of AITs and MIBI imaging has potential in the treatment of thyroid diseases. Advances in knowledge: 99mTc-MIBI imaging is a useful method for the diagnosis of AIT. It can distinguish different types of AITs especially for mixed-type AIT, which is usually difficult to treat. 99mTc-MIBI has potential advantages over conventional methods in the efficient treatment of AIT. PMID:28106465

Viable myocardium scintigraphy with intravenous nitroglycerine by computed tomography with Tc-99m (MIBI).

PubMed

Ramos Filho, José; Nascimento, Marcos Welber; Silva, Rafael Mariano Gislon da; Camargo, Thiago Negrini de; Almeida, Roberto Simões de; Lima, Eloá Jacinto

2008-09-01

The selection of patients with chronic coronary disease for recanalization is based on the detection of the affected myocardium that is potentially viable. To evaluate the potentially viable ischemic myocardium through single photon emission computed tomography (SPECT) with MIBI after a maximum tolerated dose of I.V. nitroglycerin. We prospectively investigated by SPECT with Tc-99m (MIBI), from April 2004 to November 2005, 40 patients (mean age: 62 +/- 8.9 yrs, 30 men) with coronary obstruction demonstrated angiographically; the myocardium scintigraphy was carried out at rest and after intravenous (I.V.) nitroglycerin, which was started at a dose of 1 microg/kg/min and increased every minute until the systolic blood pressure decreased by 20 mmHg. The decrease in the perfusion of the segments was classified as moderate or severe and compared after the nitroglycerin. The angiographic, hemodynamic and myocardial perfusion variables were analyzed. We analyzed 680 myocardial segments at rest: 538 with a homogenous distribution and 142 with hypoperfusion (54 with moderate and 88 with severe decrease). After the nitroglycerin, there was an increase in the perfusion in 19 (47.5%) of 40 patients and 55 of 142 segments became viable: 33 (61.1%) with moderate and 22 (25%) with severe decrease; both presented a significant increase in the radiotracer distribution (p < 0.001, Chi-square). One of the components with Tc-99m is Tc-99m 2-methoxy-isobutyl-isonitrile (MIBI), which, when used with an optimized dose of I.V. nitroglycerin, can increase the radiotracer uptake in areas with moderate and severe hypoperfusion. The results of the present study suggest the increase in the Tc-99m (MIBI) sensitivity by nitroglycerin for the detection of viable myocardium.

Low cholesterol level associated with severity and outcome of spontaneous intracerebral hemorrhage: Results from Taiwan Stroke Registry

PubMed Central

Chen, Yu-Wei; Li, Chen-Hua; Yang, Chih-Dong; Liu, Chung-Hsiang; Chen, Chih-Hung; Sheu, Jau-Jiuan; Lin, Shinn-Kuang; Chen, An-Chih; Chen, Ping-Kun; Chen, Po-Lin; Yeh, Chung-Hsin; Chen, Jiunn-Rong; Hsiao, Yu-Jen; Lin, Ching-Huang; Hsu, Shih-Pin; Chen, Tsang-Shan; Sung, Sheng-Feng; Yu, Shih-Chieh; Muo, Chih-Hsin; Wen, Chi Pang; Sung, Fung-Chang; Jeng, Jiann-Shing; Hsu, Chung Y.

2017-01-01

The relationship between cholesterol level and hemorrhagic stroke is inconclusive. We hypothesized that low cholesterol levels may have association with intracerebral hemorrhage (ICH) severity at admission and 3-month outcomes. This study used data obtained from a multi-center stroke registry program in Taiwan. We categorized acute spontaneous ICH patients, based on their baseline levels of total cholesterol (TC) measured at admission, into 3 groups with <160, 160–200 and >200 mg/dL of TC. We evaluated risk of having initial stroke severity, with National Institutes of Health Stroke Scale (NIHSS) >15 and unfavorable outcomes (modified Rankin Scale [mRS] score >2, 3-month mortality) after ICH by the TC group. A total of 2444 ICH patients (mean age 62.5±14.2 years; 64.2% men) were included in this study and 854 (34.9%) of them had baseline TC <160 mg/dL. Patients with TC <160 mg/dL presented more often severe neurological deficit (NIHSS >15), with an adjusted odds ratio [aOR] of 1.80; 95% confidence interval [CI], 1.41–2.30), and 3-month mRS >2 (aOR, 1.41; 95% CI, 1.11–1.78) using patients with TC >200 mg/dL as reference. Those with TC >160 mg/dL and body mass index (BMI) <22 kg/m2 had higher risk of 3-month mortality (aOR 3.94, 95% CI 1.76–8.80). Prior use of lipid-lowering drugs (2.8% of the ICH population) was not associated with initial severity and 3-month outcomes. A total cholesterol level lower than 160 mg/dL was common in patients with acute ICH and was associated with greater neurological severity on presentation and poor 3-month outcomes, especially with lower BMI. PMID:28422955

Factors associated with fear of falling in people with Parkinson’s disease

PubMed Central

2014-01-01

Background This study aimed to comprehensibly investigate potential contributing factors to fear of falling (FOF) among people with idiopathic Parkinson’s disease (PD). Methods The study included 104 people with PD. Mean (SD) age and PD-duration were 68 (9.4) and 5 (4.2) years, respectively, and the participants’ PD-symptoms were relatively mild. FOF (the dependent variable) was investigated with the Swedish version of the Falls Efficacy Scale, i.e. FES(S). The first multiple linear regression model replicated a previous study and independent variables targeted: walking difficulties in daily life; freezing of gait; dyskinesia; fatigue; need of help in daily activities; age; PD-duration; history of falls/near falls and pain. Model II included also the following clinically assessed variables: motor symptoms, cognitive functions, gait speed, dual-task difficulties and functional balance performance as well as reactive postural responses. Results Both regression models showed that the strongest contributing factor to FOF was walking difficulties, i.e. explaining 60% and 64% of the variance in FOF-scores, respectively. Other significant independent variables in both models were needing help from others in daily activities and fatigue. Functional balance was the only clinical variable contributing additional significant information to model I, increasing the explained variance from 66% to 73%. Conclusions The results imply that one should primarily target walking difficulties in daily life in order to reduce FOF in people mildly affected by PD. This finding applies even when considering a broad variety of aspects not previously considered in PD-studies targeting FOF. Functional balance performance, dependence in daily activities, and fatigue were also independently associated with FOF, but to a lesser extent. Longitudinal studies are warranted to gain an increased understanding of predictors of FOF in PD and who is at risk of developing a FOF. PMID:24456482

Impact of Indocyanine Green for Sentinel Lymph Node Mapping in Early Stage Endometrial and Cervical Cancer: Comparison with Conventional Radiotracer (99m)Tc and/or Blue Dye.

PubMed

Buda, Alessandro; Crivellaro, Cinzia; Elisei, Federica; Di Martino, Giampaolo; Guerra, Luca; De Ponti, Elena; Cuzzocrea, Marco; Giuliani, Daniela; Sina, Federica; Magni, Sonia; Landoni, Claudio; Milani, Rodolfo

2016-07-01

To compare the detection rate (DR) and bilateral optimal mapping (OM) of sentinel lymph nodes (SLNs) in women with endometrial and cervical cancer using indocyanine green (ICG) versus the standard technetium-99m radiocolloid ((99m)Tc) radiotracer plus methylene or isosulfan blue, or blue dye alone. From October 2010 to May 2015, 163 women with stage I endometrial or cervical cancer (118 endometrial and 45 cervical cancer) underwent SLN mapping with (99m)Tc with blue dye, blue dye alone, or ICG. DR and bilateral OM of ICG were compared respectively with the results obtained using the standard (99m)Tc radiotracer with blue dye, or blue dye alone. SLN mapping with (99m)Tc radiotracer with blue dye was performed on 77 of 163 women, 38 with blue dye only and 48 with ICG. The overall DR of SLN mapping was 97, 89, and 100 % for (99m)Tc with blue dye, blue dye alone, and ICG, respectively. The bilateral OM rate for ICG was 85 %-significantly higher than the 58 % obtained with (99m)Tc with blue dye (p = 0.003) and the 54 % for blue dye (p = 0.001). Thirty-one women (19 %) had positive SLNs. Sensitivity and negative predictive value of SLN were 100 % for all techniques. SLNs mapping using ICG demonstrated higher DR compared to other modalities. In addition, ICG was significantly superior to (99m)Tc with blue dye in terms of bilateral OM in women with early stage endometrial and cervical cancer. The higher number of bilateral OM may consequently reduce the overall number of complete lymphadenectomies, reducing the duration and additional costs of surgical treatment.

Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma.

PubMed

Czepczyński, Rafał; Parisella, Maria Gemma; Kosowicz, Jerzy; Mikołajczak, Renata; Ziemnicka, Katarzyna; Gryczyńska, Maria; Sowiński, Jerzy; Signore, Alberto

2007-10-01

Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue (99m)Tc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. Forty-five patients with MTC, aged 14-83 years, were investigated. Scintigraphy using (99m)Tc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, (99m)Tc(V)-DMSA, (131)I-MIBG, (99m)Tc-MDP, (111)In-DTPA-octreotide and (18)F-FDG-PET) and compared with (99m)Tc-EDDA/HYNIC-TOC. In group 1 (eight patients before thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2 (six patients with remission), a false positive result was found in one patient; in the remaining five patients, no pathological foci were visualised. In group 3 (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true positive in 23 patients (74.2%): uptake in the thyroid bed was found in five patients, in the lymph nodes in 18 and in bone metastases in four. Using (99m)Tc-EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity 83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive value 38.5%. (99m)Tc-EDDA/HYNIC-TOC is clinically useful for scintigraphy in the follow-up of patients with MTC. It can be used in clinical practice for preoperative evaluation, for localisation of local recurrence or distant metastases and particularly for therapy decision making.

Hürthle cell tumor dwelling in hot thyroid nodules: preoperative detection with technetium-99m-MIBI dual-phase scintigraphy.

PubMed

Vattimo, A; Bertelli, P; Cintorino, M; Burroni, L; Volterrani, D; Vella, A; Lazzi, S

1998-05-01

Single injection dual-phase scintigraphy (early and late acquisitions) with 99mTc-MIBI was used to differentiate benign and malignant hot thyroid nodules. Thirteen euthyroid and two hyperthyroid patients displaying a hot thyroid nodule on the 99mTc scan due to an autonomously functioning thyroid nodule (AFTN) underwent early (15-30 min) and late (3-4 hr) thyroid scintigraphy after the administration of 740-1000 MBq 99mTc-MIBI. Visual scoring was done to assess nodular tracer uptake and retention. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late image and the washout rates (WO) from the nodule and thyroidal tissue were measured. All patients underwent thyroid surgery. Histopathology revealed a Hürthle cell tumor in three nodules, a benign adenoma with oxyphilic metaplasia in two nodules and a benign adenoma without oxyphilic cells in the remaining 10 nodules. The Hürthle cell tumor nodules displayed intense and persistent uptake of 99mTc-MIBI (N/T was 2.81 +/- 0.52 and 5.53 +/- 1.06 in early and late images, respectively; WO from the nodule was 12.33 +/- 0.47, WO from the thyroidal tissue was 22.00 +/- 3.56). The benign nodules showed intense uptake in the early image and intense uptake to absent retention in the late image (N/T was 2.94 +/- 1.31 and 1.62 +/- 0.50 in the early and late images, respectively; WO from the nodule was 20.25 +/- 2.92, WO from the thyroidal tissue was 20.33 +/- 2.92). Single injection dual-phase 99mTc-MIBI scintigraphy of the thyroid with AFTN can identify nodules as a result of the activity of a Hürthle cell tumor, since these tumors cause intense and persistent tracer uptake in contrast with a benign AFTN.

Regional heterogeneity in cardiac sympathetic innervation in acute myocardial infarction: relationship with myocardial oedema on magnetic resonance.

PubMed

Gimelli, Alessia; Masci, Pier Giorgio; Liga, Riccardo; Grigoratos, Chrysanthos; Pasanisi, Emilio Maria; Lombardi, Massimo; Marzullo, Paolo

2014-09-01

To assess the relationships between myocardial structure and function on cardiac magnetic resonance (CMR) imaging and sympathetic tone on (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy early after myocardial infarction (MI). Ten patients underwent (123)I-MIBG and (99m)Tc-tetrofosmin rest cadmium zinc telluride scintigraphy 4 ± 1 days after MI. The segmental left ventricular (LV) relative radiotracer uptake of both (99m)Tc-tetrofosmin and early (123)I-MIBG was calculated. The day after scintigraphy, on CMR imaging, the extent of ischaemia-related oedema and of myocardial fibrosis (late gadolinium enhancement, LGE) was assessed. Accordingly, the extent of oedema and LGE was evaluated for each segment and segmental wall thickening determined. Based on LGE distribution, LV segments were categorized as "infarcted" (56 segments), "adjacent" (66 segments) or "remote" (48 segments). Infarcted segments showed a more depressed systolic wall thickening and greater extent of oedema than adjacent segments (p < 0.001) and remote segments (p < 0.001). Interestingly, while uptake of (99m)Tc-tetrofosmin was significantly depressed only in infarcted segments (p < 0.001 vs. both adjacent and remote segments), uptake of (123)I-MIBG was impaired not only in infarcted segments (p < 0.001 vs. remote) but also in adjacent segments (p = 0.024 vs. remote segments). At the regional level, after correction for (99m)Tc-tetrofosmin and LGE distribution, segmental (123)I-MIBG uptake (p < 0.001) remained an independent predictor of ischaemia-related oedema. After acute MI the regional impairment of sympathetic tone extends beyond the area of altered myocardial perfusion and is associated with myocardial oedema.

Evaluation of left ventricular function using electrocardiographically gated myocardial SPECT with (123)I-labeled fatty acid analog.

PubMed

Nanasato, M; Ando, A; Isobe, S; Nonokawa, M; Hirayama, H; Tsuboi, N; Ito, T; Hirai, M; Yokota, M; Saito, H

2001-12-01

Electrocardiographically (ECG) gated myocardial SPECT with (99m)Tc-tetrofosmin has been used widely to assess left ventricular (LV) function. However, the accuracy of variables using ECG gated myocardial SPECT with beta-methyl-p-(123)I-iodophenylpentadecanoic acid (BMIPP) has not been well defined. Thirty-six patients (29 men, 7 women; mean age, 61.6 +/- 15.6 y) with ischemic heart disease underwent ECG gated myocardial SPECT with (123)I-BMIPP and with (99m)Tc-tetrofosmin and left ventriculography (LVG) within 1 wk. LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV) were determined on gated SPECT using commercially available software for automatic data analysis. These volume-related items on LVG were calculated with an area-length method and were estimated by 2 independent observers to evaluate interobserver validity. The regional wall motion with these methods was assessed visually. LVEF was 41.1% +/- 12.5% on gated SPECT with (123)I-BMIPP, 44.5% +/- 13.1% on gated SPECT with (99m)Tc-tetrofosmin, and 46.0% +/- 12.7% on LVG. Global LV function and regional wall motion between both gated SPECT procedures had excellent correlation (LVEF, r = 0.943; LVEDV, r = 0.934; LVESV, r = 0.952; regional wall motion, kappa = 0.92). However, the correlations of global LV function and regional wall motion between each gated SPECT and LVG were significantly lower. Gated SPECT with (123)I-BMIPP showed the same interobserver validity as gated SPECT with (99m)Tc-tetrofosmin. Gated SPECT with (123)I-BMIPP provides high accuracy with regard to LV function and is sufficiently applicable for use in clinical SPECT. This technique can simultaneously reveal myocardial fatty acid metabolism and LV function, which may be useful to evaluate various cardiac diseases.

18F-Fluorosulfate for PET Imaging of the Sodium-Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo.

PubMed

Khoshnevisan, Alex; Chuamsaamarkkee, Krisanat; Boudjemeline, Mehdi; Jackson, Alex; Smith, Gareth E; Gee, Antony D; Fruhwirth, Gilbert O; Blower, Philip J

2017-01-01

Anion transport by the human sodium-iodide symporter (hNIS) is an established target for molecular imaging and radionuclide therapy. Current radiotracers for PET of hNIS expression are limited to 124 I - and 18 F-BF 4 - We sought new 18 F-labeled hNIS substrates offering higher specific activity, higher affinity, and simpler radiochemical synthesis than 18 F-BF 4 - METHODS: The ability of a range of anions, some containing fluorine, to block 99m TcO 4 - uptake in hNIS-expressing cells was measured. SO 3 F - emerged as a promising candidate. 18 F-SO 3 F - was synthesized by reaction of 18 F - with SO 3 -pyridine complex in MeCN and purified using alumina and quaternary methyl ammonium solid-phase extraction cartridges. Chemical and radiochemical purity and serum stability were determined by radiochromatography. Radiotracer uptake and efflux in hNIS-transduced HCT116-C19 cells and the hNIS-negative parent cell line were evaluated in vitro in the presence and absence of a known competitive inhibitor (NaClO 4 ). PET/CT imaging and ex vivo biodistribution measurement were conducted on BALB/c mice, with and without NaClO 4 inhibition. Fluorosulfate was identified as a potent inhibitor of 99m TcO 4 - uptake via hNIS in vitro (half-maximal inhibitory concentration, 0.55-0.56 μM (in comparison with 0.29-4.5 μM for BF 4 - , 0.07 μM for TcO 4 - , and 2.7-4.7 μM for I - ). Radiolabeling to produce 18 F-SO 3 F - was simple and afforded high radiochemical purity suitable for biologic evaluation (radiochemical purity > 95%, decay-corrected radiochemical yield = 31.6%, specific activity ≥ 48.5 GBq/μmol). Specific, blockable hNIS-mediated uptake in HCT116-C19 cells was observed in vitro, and PET/CT imaging of normal mice showed uptake in thyroid, salivary glands (percentage injected dose/g at 30 min, 563 ± 140 and 32 ± 9, respectively), and stomach (percentage injected dose/g at 90 min, 68 ± 21). Fluorosulfate is a high-affinity hNIS substrate. 18 F-SO 3 F - is easily synthesized in high yield and very high specific activity and is a promising candidate for preclinical and clinical PET imaging of hNIS expression and thyroid-related disease; it is the first example of in vivo PET imaging with a tracer containing an S- 18 F bond. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Walking economy in people with Parkinson's disease.

PubMed

Christiansen, Cory L; Schenkman, Margaret L; McFann, Kim; Wolfe, Pamela; Kohrt, Wendy M

2009-07-30

Gait dysfunction is an early problem identified by patients with Parkinson's disease (PD). Alterations in gait may result in an increase in the energy cost of walking (i.e., walking economy). The purpose of this study was to determine whether walking economy is atypical in patients with PD when compared with healthy controls. A secondary purpose was to evaluate the associations of age, sex, and level of disease severity with walking economy in patients with PD. The rate of oxygen consumption (VO(2)) and other responses to treadmill walking were compared in 90 patients (64.4 +/- 10.3 years) and 44 controls (64.6 +/- 7.3 years) at several walking speeds. Pearson correlation coefficients (r) were calculated to determine relationships of age, sex, and disease state with walking economy in PD patients. Walking economy was significantly worse in PD patients than in controls at all speeds above 1.0 mph. Across all speeds, VO(2) was 6 to 10% higher in PD patients. Heart rate, minute ventilation, respiratory exchange ratio, and rating of perceived exertion were correspondingly elevated. No significant relationship of age, sex, or UPDRS score with VO(2) was found for patients with PD. The findings suggest that the physiologic stress of daily physical activities is increased in patients with early to mid-stage PD, and this may contribute to the elevated level of fatigue that is characteristic of PD. Copyright 2009 Movement Disorder Society.

Comparison of the pressure dependences of Tc in the trivalent d -electron superconductors Sc, Y, La, and Lu up to megabar pressures

NASA Astrophysics Data System (ADS)

Debessai, M.; Hamlin, J. J.; Schilling, J. S.

2008-08-01

Whereas double hcp (dhcp) La superconducts at ambient pressure with Tc≃5K , the other trivalent d -electron metals Sc, Y, and Lu only superconduct if high pressures are applied. Earlier measurements of the pressure dependence of Tc for Sc and Lu metal are here extended to much higher pressures. Whereas Tc for Lu increases monotonically with pressure to 12.4 K at 174 GPa (1.74 Mbar), Tc for Sc reaches 19.6 K at 107 GPa, the second highest value observed for any elemental superconductor. At higher pressures a phase transition occurs whereupon Tc drops to 8.31 K at 111 GPa. The Tc(P) dependences for Sc and Lu are compared with those of Y and La. An interesting correlation is pointed out between the value of Tc and the fractional free volume available to the conduction electrons outside the ion cores, a quantity which is directly related to the number of d electrons in the conduction band.

SPECT/CT with 99mTc-MAA in radioembolization with 90Y microspheres in patients with hepatocellular cancer.

PubMed

Hamami, Monia E; Poeppel, Thorsten D; Müller, Stephan; Heusner, Till; Bockisch, Andreas; Hilgard, Philipp; Antoch, Gerald

2009-05-01

Radioembolization with (90)Y microspheres is a novel treatment for hepatic tumors. Generally, hepatic arteriography and (99m)Tc-macroaggregated albumin (MAA) scanning are performed before selective internal radiation therapy to detect extrahepatic shunting to the lung or the gastrointestinal tract. Whereas previous studies have used only planar or SPECT scans, the present study used (99m)Tc-MAA SPECT/CT scintigraphy (SPECT with integrated low-dose CT) to evaluate whether SPECT/CT and additional diagnostic contrast-enhanced CT before radioembolization with (90)Y microspheres are superior to SPECT or planar imaging alone for detection of gastrointestinal shunting. In a prospective study, we enrolled 58 patients (mean age, 66 y; SD, 12 y; 10 women and 48 men) with hepatocellular carcinoma who underwent hepatic arteriography and scintigraphy with (99m)Tc-MAA using planar imaging, SPECT, and SPECT with integrated low-dose CT of the upper abdomen (acquired with a hybrid SPECT/CT camera). The ability of the different imaging modalities to detect extrahepatic MAA shunting was compared. Patient follow-up of a mean of 180 d served as the standard of reference. Gastrointestinal shunting was revealed by planar imaging in 4, by SPECT in 9, and by SPECT/CT in 16 of the 68 examinations. For planar imaging, the sensitivity for detection of gastrointestinal shunting was 25%, the specificity 87%, and the accuracy 72%. For SPECT without CT, the sensitivity was 56%, the specificity 87%, and the accuracy 79%. SPECT with CT fusion had a sensitivity of 100%, a specificity of 94%, and an accuracy of 96%. In 3 patients, MAA deposits in the portal vein could accurately be attributed to tumor thrombus only with additional information from contrast-enhanced CT. The follow-up did not show any gastrointestinal complications. SPECT with integrated low-dose CT using (99m)Tc-MAA is beneficial in radioembolization with (90)Y microspheres because it increases the sensitivity and specificity of (99m)Tc-MAA SPECT when detecting extrahepatic arterial shunting. The overall low risk of gastrointestinal complications in radioembolization may therefore be further reduced by SPECT/CT.

Synthesis and characterization of fac-Re(CO)3-aspartic-N-monoacetic acid, a structural analogue of a potential new renal tracer, fac-99mTc(CO)3(ASMA)

PubMed Central

Klenc, Jeffrey; Lipowska, Malgorzata; Taylor, Andrew T.; Marzilli, Luigi G.

2013-01-01

The reaction of an aminopolycarboxylate ligand, aspartic-N-monoacetic acid (ASMA), with [Re(CO)3(H2O)3]+ was examined. The tridentate coordination of ASMA to this ReI tricarbonyl precursor yielded fac-Re(CO)3(ASMA) as a mixture of diastereomers. The chemistry is analogous to that of the TcI tricarbonyl complex, which yields fac-99mTc(CO)3(ASMA) under similar conditions. The formation, structure, and isomerization of fac-Re(CO)3(ASMA) products were characterized by HPLC, 1H NMR spectroscopy, and X-ray crystallography. The two major fac-Re(CO)3(ASMA) diastereomeric products each have a linear ONO coordination mode with two adjacent five-membered chelate rings, but they differ in the endo or exo orientation of the uncoordinated acetate group, in agreement with expectations based on previous studies. Conditions have been identified for the expedient isomerization of fac-Re(CO)3(ASMA) to a mixture consisting primarily of one major product. Because different isomeric species typically have different pharmacokinetic characteristics, these conditions may provide for the practical isolation of a single 99mTc(CO)3(ASMA) species, thus allowing the isolation of the isomer that has optimal imaging and pharmacokinetic characteristics. This information will aid in the design of future 99mTc radiopharmaceuticals. PMID:24273448

The effect of maleate induced proximal tubular dysfunction on the renal handling of Tc-99m DMSA in the rat

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

Provoost, A.P.; Van Aken, M.

1984-01-01

In the healthy kidney Tc-99m DMSA accumulates in the proximal tubular cells. Consequently, impairment of the reabsorptive function of these cells may alter the renal handling of this static renal imaging agent. The authors investigated in rats the effects of a sodiummaleate (Ma) (2mmol/kg iv) induced proximal tubular dysfunction on the renal accumulation and excretion of Tc-99m DMSA. Such a treatment results in a moderate fall of the glomerular filtration rate, glycosuria, aminoaciduria and a tubular proteinuria. In 7 adult male Wistar rats, Tc-99m DMSA scans were taken before Ma, on the day of treatment, and 1 week thereafter. Themore » accumulation of Tc-99m DMSA in kidneys (Ki) and bladder (Bl) was determined at 1, 2, 4, and 24 hours after i.v. injection. The results, expressed as a percentage of the injected dose, are presented. The findings show that a reversible Ma induced impairment of the proximal reabsorptive capacity severely alters the renal tubular handling of Tc-99m DMSA. In contrast to the control situation, only a small fraction of the DMSA is retained in the kidney and the majority is transported directly to the urinary bladder. When similar alterations are observed in clinical Tc-99m DMSA scans, this may be an indication of an impairment of the proximal tubular function.« less

Tea Catechins Protect Goat Skeletal Muscle against H₂O₂-Induced Oxidative Stress by Modulating Expression of Phase 2 Antioxidant Enzymes.

PubMed

Zhong, Rong-Zhen; Fang, Yi; Qin, Gui-Xin; Li, Hao-Yang; Zhou, Dao-Wei

2015-09-16

To study the mechanisms of tea catechins (TCs) in goat muscles against oxidative stress, skeletal muscle cells (SMCs) induced by H2O2 or not were incubated with TCs or 3H-1,2-dithiole-3-thione (D3T) and were defined as H2O2, H2O2D3T, H2O2TC, D3T, and TC treatments, respectively. Results showed that, similar to effects of D3T, TCs regulated mRNA and protein expression of antioxidant enzymes by suppressing Keap1 protein expression in SMCs from 1.58 ± 0.12 to 0.71 ± 0.21 and 1.03 ± 0.11 in H2O2TC and TC groups, respectively; however, effects differed in oxidative condition of cells and among enzymes. In stressed cells, TCs increased catalase and glutathione S-transferases (GST) activities (P < 0.001), whereas both enzymes' activities decreased (P < 0.001) to 2.97 ± 0.37 U/mg protein or 42.1 ± 1.85 mU/mg protein, respectively, in unstressed SMCs. Subsequently, an in vivo experiment in goats fed grain supplemented with TCs or D3T following infusion with H2O2 was conducted to further verify mechanisms of TC action. As seen in vitro, TCs reduced Keap1 protein expression (P < 0.001) from 2.11 ± 0.37 to 1.34 ± 0.13 and 1.43 ± 0.23 in H2O2TC and TC groups, respectively, in muscle. However, dietary TCs increased plasma CuZn superoxide dismutase and GST activities (P < 0.001) regardless of oxidative stress. Moreover, feeding TCs to goats under both conditions increased meat color and tenderness (P ≤ 0.001). In conclusion, TCs protected goat muscles against oxidative stress and subsequently improved meat quality by modulating phase 2 antioxidant enzymes and Keap1 expression.

Lack of LTP-like plasticity in primary motor cortex in Parkinson's disease.

PubMed

Suppa, A; Marsili, L; Belvisi, D; Conte, A; Iezzi, E; Modugno, N; Fabbrini, G; Berardelli, A

2011-02-01

In this study in patients with Parkinson's disease (PD), off and on dopaminergic therapy, with and without L-dopa-induced dyskinesias (LIDs), we tested intermittent theta-burst stimulation (iTBS), a technique currently used for non-invasively inducing long-term potentiation (LTP)-like plasticity in primary motor cortex (M1). The study group comprised 20 PD patients on and off dopaminergic therapy (11 patients without and 9 patients with LIDs), and 14 age-matched healthy subjects. Patients had mild-to-moderate PD, and no additional neuropsychiatric disorders. We clinically evaluated patients using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Unified Dyskinesia Rating Scale (UDysRS). The left M1 was conditioned with iTBS at 80% active motor threshold intensity. Twenty motor evoked potentials (MEPs) were recorded from right first interosseous muscle before and at 5, 15 and 30 min after iTBS. Between-group analysis of variance (ANOVA) testing healthy subjects versus patients with and without LIDs, on and off therapy showed a significant interaction between factors "Group" and "Time". After iTBS, MEP amplitudes in healthy subjects increased significantly at 5, 15 and 30 min (p<0.01 at all time-points) but in PD patients with and without LIDs, on and off therapy, remained unchanged. In PD patients with and without LIDs, on and off therapy iTBS fails to increase MEP responses. This finding suggests lack of iTBS-induced LTP-like plasticity in M1 in PD regardless of patients' clinical features. Copyright © 2010 Elsevier Inc. All rights reserved.

Influence of the chelator structures on the stability of Re and Tc tricarbonyl complexes with iminodiacetic acid tridentate ligands: a computational study.

PubMed

Hernández-Valdés, Daniel; Rodríguez-Riera, Zalua; Díaz-García, Alicia; Benoist, Eric; Jáuregui-Haza, Ulises

2016-08-01

The development of novel radiopharmaceuticals for nuclear medicine based on M(CO)3 (M = Tc, Re) complexes has attracted great attention. The versatility of this core and the easy production of the fac-[M(CO)3(H2O)3](+) precursor could explain this interest. The main characteristics of these tricarbonyl complexes are the high substitution stability of the three CO ligands and the corresponding lability of the coordinated water molecules, yielding, via easy exchange of a variety of bi- and tridentate ligands, complexes xof very high kinetic stability. Here, a computational study of different tricarbonyl complexes of Re(I) and Tc(I) was performed using density functional theory. The solvent effect was simulated using the polarizable continuum model. These structures were used as a starting point to investigate the relative stabilities of tricarbonyl complexes with various tridentate ligands. These complexes included an iminodiacetic acid unit for tridentate coordination to the fac-[M(CO)3](+) moiety (M = Re, Tc), an aromatic ring system bearing a functional group (-NO2, -NH2, and -Cl) as a linking site model, and a tethering moiety (a methylene, ethylene, propylene butylene, or pentylene bridge) between the linking and coordinating sites. The optimized complexes showed geometries comparable to those inferred from X-ray data. In general, the Re complexes were more stable than the corresponding Tc complexes. Furthermore, using NH2 as the functional group, a medium length carbon chain, and ortho substitution increased complex stability. All of the bonds involving the metal center presented a closed shell interaction with dative or covalent character, and the strength of these bonds decreased in the sequence Tc-CO > Tc-O > Tc-N.

Radiosynthesis and Biodistribution of 99mTc-Metronidazole as an Escherichia coli Infection Imaging Radiopharmaceutical.

PubMed

Iqbal, Anam; Naqvi, Syed Ali Raza; Rasheed, Rashid; Mansha, Asim; Ahmad, Matloob; Zahoor, Ameer Fawad

2018-05-01

Bacterial infection poses life-threatening challenge to humanity and stimulates to the researchers for developing better diagnostic and therapeutic agents complying with existing theranostic techniques. Nuclear medicine technique helps to visualize hard-to-diagnose deep-seated bacterial infections using radionuclide-labeled tracer agents. Metronidazole is an antiprotozoal antibiotic that serves as a preeminent anaerobic chemotherapeutic agent. The aim of this study was to develop technetium-99m-labeled metronidazole radiotracer for the detection of deep-seated bacterial infections. Radiosynthesis of 99m Tc-metronidazole was carried by reacting reduced technetium-99m and metronidazole at neutral pH for 30 min. The stannous chloride dihydrate was used as the reducing agent. At optimum radiolabeling conditions, ~ 94% radiochemical was obtained. Quality control analysis was carried out with a chromatographic paper and instant thin-layer chromatographic analysis. The biodistribution study of radiochemical was performed using Escherichia coli bacterial infection-induced rat model. The scintigraphic study was performed using E. coli bacterial infection-induced rabbit model. The results showed promising accumulation at the site of infection and its rapid clearance from the body. The tracer showed target-to-non-target ratio 5.57 ± 0.04 at 1 h post-injection. The results showed that 99m Tc-MNZ has promising potential to accumulate at E. coli bacterial infection that can be used for E. coli infection imaging.

KSC-08pd1109

NASA Image and Video Library

2008-05-03

CAPE CANAVERAL, Fla. -- At NASA's Kennedy Space Center, dawn reveals the arrival of space shuttle Discovery, secured atop the mobile launch platform below, at Launch Pad 39A to begin prelaunch processing for the STS-124 mission. The 3.4-mile journey from the Vehicle Assembly Building began at 11:47 p.m. on May 2. The shuttle arrived at the launch pad at 4:25 a.m. EDT May 3 and was secured, or hard down, by 6:06 a.m. On the 13-day mission, Discovery and its crew will deliver the Japan Aerospace Exploration Agency's Japanese Experiment Module – Pressurized Module and the Japanese Remote Manipulator System. Launch is targeted for May 31. Photo credit: NASA/Troy Cryder

KSC-08pd1106

NASA Image and Video Library

2008-05-03

CAPE CANAVERAL, Fla. -- At NASA's Kennedy Space Center, space shuttle Discovery, secured atop the mobile launch platform below, arrives at Launch Pad 39A to begin prelaunch processing for the STS-124 mission. The 3.4-mile journey from the Vehicle Assembly Building began at 11:47 p.m. on May 2. The shuttle arrived at the launch pad at 4:25 a.m. EDT May 3 and was secured, or hard down, by 6:06 a.m. On the 13-day mission, Discovery and its crew will deliver the Japan Aerospace Exploration Agency's Japanese Experiment Module – Pressurized Module and the Japanese Remote Manipulator System. Launch is targeted for May 31. Photo credit: NASA/Troy Cryder

KSC-08pd1105

NASA Image and Video Library

2008-05-03

CAPE CANAVERAL, Fla. -- This aerial view of NASA's Kennedy Space Center shows space shuttle Discovery, secured atop a mobile launch platform as it is moved into position at Launch Pad 39A to prepare for the STS-124 mission. The 3.4-mile journey from the Vehicle Assembly Building began at 11:47 p.m. on May 2. The shuttle arrived at the launch pad at 4:25 a.m. EDT May 3 and was secured, or hard down, by 6:06 a.m. On the 13-day mission, Discovery and its crew will deliver the Japan Aerospace Exploration Agency's Japanese Experiment Module – Pressurized Module and the Japanese Remote Manipulator System. Launch is targeted for May 31. Photo credit: NASA/Troy Cryder

KSC-08pd1110

NASA Image and Video Library

2008-05-03

CAPE CANAVERAL, Fla. -- At NASA's Kennedy Space Center, the sun rises upon the arrival of space shuttle Discovery, secured atop the mobile launch platform below, at Launch Pad 39A to begin prelaunch processing for the STS-124 mission. The 3.4-mile journey from the Vehicle Assembly Building began at 11:47 p.m. on May 2. The shuttle arrived at the launch pad at 4:25 a.m. EDT May 3 and was secured, or hard down, by 6:06 a.m. On the 13-day mission, Discovery and its crew will deliver the Japan Aerospace Exploration Agency's Japanese Experiment Module – Pressurized Module and the Japanese Remote Manipulator System. Launch is targeted for May 31. Photo credit: NASA/Troy Cryder

Evaluation of a novel Arg-Gly-Asp-conjugated α-melanocyte stimulating hormone hybrid peptide for potential melanoma therapy.

PubMed

Yang, Jianquan; Guo, Haixun; Gallazzi, Fabio; Berwick, Marianne; Padilla, R Steven; Miao, Yubin

2009-08-19

The purpose of this study was to determine whether Arg-Gly-Asp (RGD)-conjugated α-melanocyte stimulating hormone (α-MSH) hybrid peptide could be employed to target melanocortin-1 (MC1) receptor for potential melanoma therapy. The RGD motif {cyclic(Arg-Gly-Asp-DTyr-Asp)} was coupled to [Cys(3,4,10), DPhe(7), Arg(11)]α-MSH(3-13) {(Arg(11))CCMSH} to generate RGD-Lys-(Arg(11))CCMSH hybrid peptide. The MC1 receptor binding affinity of RGD-Lys-(Arg(11))CCMSH was determined in B16/F1 melanoma cells. The internalization and efflux, melanoma targeting and pharmacokinetic properties and single photon emission computed tomography/CT (SPECT/CT) imaging of (99m)Tc-RGD-Lys-(Arg(11))CCMSH were determined in B16/F1 melanoma cells and melanoma-bearing C57 mice. Clonogenic cytotoxic effect of RGD-Lys-(Arg(11))CCMSH was examined in B16/F1 melanoma cells. RGD-Lys-(Arg(11))CCMSH displayed 2.1 nM MC1 receptor binding affinity. (99m)Tc-RGD-Lys-(Arg(11))CCMSH showed rapid internalization and extended retention in B16/F1 cells. The cellular uptake of (99m)Tc-RGD-Lys-(Arg(11))CCMSH was MC1 receptor-mediated. (99m)Tc-RGD-Lys-(Arg(11))CCMSH exhibited high tumor uptake (14.83 ± 2.94% ID/g 2 h postinjection) and prolonged tumor retention (7.59 ± 2.04% ID/g 24 h postinjection) in B16/F1 melanoma-bearing mice. Nontarget organ uptakes were generally low except for the kidneys. Whole-body clearance of (99m)Tc-RGD-Lys-(Arg(11))CCMSH was rapid, with approximately 62% of the injected radioactivity cleared through the urinary system by 2 h postinjection. Flank melanoma tumors were clearly imaged by small animal SPECT/CT using (99m)Tc-RGD-Lys-(Arg(11))CCMSH as an imaging probe 2 h postinjection. Single treatment (3 h incubation) with 100 nM of RGD-Lys-(Arg(11))CCMSH significantly (p < 0.05) decreased the clonogenic survival of B16/F1 cells by 65% compared to the untreated control cells. Favorable melanoma targeting property of (99m)Tc-RGD-Lys-(Arg(11))CCMSH and remarkable cytotoxic effect of RGD-Lys-(Arg(11))CCMSH in B16/F1 cells warranted the further evaluation of (188)Re-labeled α-MSH hybrid peptides as novel therapeutic peptides for melanoma treatment once the strategies of amino acid coinjection or structural modification of peptide sequence substantially reduce the renal uptake.

WE-AB-204-12: Dosimetry at the Sub-Cellular Scale of Auger-Electron Emitter 99m-Tc in a Mouse Single Thyroid Follicle Model

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

Taborda, A; Benabdallah, N; Desbree, A

2015-06-15

Purpose: To perform a dosimetry study at the sub-cellular scale of Auger-electron emitter 99m-Tc using a mouse single thyroid cellular model to investigate the contribution of the 99m-Tc Auger-electrons to the absorbed dose and possible link to the thyroid stunning in in vivo experiments in mice, recently reported in literature. Methods: The simulation of S-values for Auger-electron emitting radionuclides was performed using both the recent MCNP6 software and the Geant4-DNA extension of the Geant4 toolkit. The dosimetric calculations were validated through comparison with results from literature, using a simple model of a single cell consisting of two concentric spheres ofmore » unit density water and for six Auger-electron emitting radionuclides. Furthermore, the S-values were calculated using a single thyroid follicle model for uniformly distributed 123-I and 125-I radionuclides and compared with published S-values. After validation, the simulation of the S-values was performed for the 99m-Tc radionuclide within the several mouse thyroid follicle cellular compartments, considering the radiative and non-radiative transitions of the 99m-Tc radiation spectrum. Results: The calculated S-values using MCNP6 are in good agreement with the results from literature, validating its use for the 99m-Tc S-values calculations. The most significant absorbed dose corresponds to the case where the radionuclide is uniformly distributed in the follicular cell’s nucleus, with a S-value of 7.8 mGy/disintegration, due mainly to the absorbed Auger-electrons. The results show that, at a sub-cellular scale, the emitted X-rays and gamma particles do not contribute significantly to the absorbed dose. Conclusion: In this work, MCNP6 was validated for dosimetric studies at the sub-cellular scale. It was shown that the contribution of the Auger-electrons to the absorbed dose is important at this scale compared to the emitted photons’ contribution and can’t be neglected. The obtained S-values of Auger-electron emitting 99m-Tc radionuclide will be presented and discussed.« less

Semicomprehensive analysis of the postnatal age-related changes in the mRNA expression of sex steroidogenic enzymes and sex steroid receptors in the male rat hippocampus.

PubMed

Kimoto, Tetsuya; Ishii, Hirotaka; Higo, Shimpei; Hojo, Yasushi; Kawato, Suguru

2010-12-01

Although sex steroids play a crucial role in the postnatal brain development, the age-related changes in the hippocampal steroidogenesis remain largely unknown. We performed comprehensive investigations for the mRNA expressions of 26 sex steroidogenic enzymes/proteins and three sex steroid receptors in the male rat hippocampus, at the ages of postnatal day (PD) 1, PD4, PD7, PD10, PD14, 4 wk, and 12 wk (adult), by RT-PCR/Southern blotting analysis. The relative expression levels of these enzymes/receptors at PD1 were Srd5a1 > Star > Ar ∼ Hsd17b4 ∼ Hsd17b1 ∼ Hsd17b7 ∼ Esr1 ∼ Srd5a2 > Hsd17b3 > Esr2 > Cyp11a1 > Cyp17a1 > Cyp19a1 ∼ Hsd17b2 > 3β-hydroxysteroid dehydrogenase I. The mRNA levels of essential enzymes for progesterone/testosterone/estradiol metabolisms (Cyp17a1, Hsd17b7, and Cyp19a1) were approximately constant between PD1 and PD14 and then declined toward the adult levels. Cyp11a1 increased during PD4-PD14 and then considerably decreased toward the adult level (∼8% of PD1). Hsd17b1, Hsd17b2, and 3β-hydroxysteroid dehydrogenase I mRNA decreased approximately monotonously. Hsd17b3 increased to approximately 200% of PD1 during PD4-PD14 and was maintained at this high level. The 5α-reductase mRNA was maintained constant (Srd5a1) or decreased monotonically (Srd5a2) toward the adult level. The Esr1 level peaked at PD4 and decreased toward the adult level, whereas Ar greatly increased during PD1-PD14 and was maintained at this high level. The Star and Hsd17b4 levels were maintained constant from neonate to adult. These results suggest that the hippocampal sex steroidogenic properties are substantially altered during the postnatal development processes, which might contribute to brain sexual maturation.

Norwegian Seismic Array (NORSAR) Phase 3

DTIC Science & Technology

1975-08-08

now finished and the results are presented in Chapter M. Chapter N is a report on the problem of using various statistical tests for discriminating...LninTcMCOoc-iouic^mcr» in —i co co —i o I ooni/irioriaioojnnHrin i m t vo " ii) m rr —ir-i^H^rcM r-j^ coton CO CM in CM o co co in in tj

8 CFR 103.7 - Fees.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., remittance may be made by bank international money order or foreign draft drawn on a financial institution in... petition for school certification—$1,700, plus a site visit fee of $655 for each location listed on the..., mutilated, or destroyed, or for a change in name—$290. Form I-94.For issuance of Arrival/Departure Record at...

Evaluation of Xpert C. difficile, BD MAX Cdiff, IMDx C. difficile for Abbott m2000, and Illumigene C. difficile Assays for Direct Detection of Toxigenic Clostridium difficile in Stool Specimens.

PubMed

Shin, Bo-Moon; Yoo, Sun Mee; Shin, Won Chang

2016-03-01

We evaluated the performance of four commercial nucleic acid amplification tests (NAATs: Xpert C. difficile, BD MAX Cdiff, IMDx C. difficile for Abbott m2000, and Illumigene C. difficile) for direct and rapid detection of Clostridium difficile toxin genes. We compared four NAATs on the same set of 339 stool specimens (303 prospective and 36 retrospective specimens) with toxigenic culture (TC). Concordance rate among four NAATs was 90.3% (306/339). Based on TC results, the sensitivity and specificity were 90.0% and 92.9% for Xpert; 86.3% and 89.3% for Max; 84.3% and 94.4% for IMDx; and 82.4% and 93.7% for Illumigene, respectively. For 306 concordant cases, there were 11 TC-negative/NAATs co-positive cases and 6 TC-positive/NAATs co-negative cases. Among 33 discordant cases, 18 were only single positive in each NAAT (Xpert, 1; Max, 12; IMDx, 1; Illumigene, 4). Positivity rates of the four NAATs were associated with those of semi-quantitative cultures, which were maximized in grade 3 (>100 colony-forming unit [CFU]) compared with grade 1 (<10 CFU). Commercial NAATs may be rapid and reliable methods for direct detection of tcdA and/or tcdB in stool specimens compared with TC. Some differences in the sensitivity of the NAATs may partly depend on the number of toxigenic C. difficile in stool specimens.

The effect of high-, moderate-, and low-fat diets on weight loss and cardiovascular disease risk factors.

PubMed

Fleming, Richard M

2002-01-01

Over 60% of Americans are overweight and a number of popular diets have been advocated, often without evidence, to alleviate this public health hazard. This study was designed to investigate the effects of several diets on weight loss, serum lipids, and other cardiovascular disease risk factors. One hundred men and women followed one of four dietary programs for 1 year: a moderate-fat (MF) program without calorie restriction (28 patients); a low-fat (LF) diet (phase I) (16) ; a MF, calorie-controlled (phase II) diet (38 patients); and a high-fat (HF) diet (18 subjects) [corrected]. Weight, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), homocysteine (Ho), and lipoprotein(a) [Lp(a)], were measured every 4th month. The TC/HDL-C ratio was calculated and fibrinogen levels were measured at baseline and after one year. The MF diet resulted in a 2.6% (NS) decrease in weight compared with 18.4% (p=0.045) decrease in patients on phase I, 12.6% (p=0.0085) decrease in patients on phase II, and 13.7% (p=0.025) decrease in those on the HF diet. TC was reduced by 5% (NS) in the MF group, 39.1% (p=0.0005) in the phase I group, and 30.4% (p=0.0001) in the phase II group. HF group had a 4.3% (NS) increase in TC. LDL-C was reduced by 6.1% (NS) on MF, 52.0% (p=0.0001) on phase I, and 38.8% (p=0.0001) on phase II. Patients on HF had a 6.0% (NS) increase in LDL-C. There were nonsignificant reductions in HDL-C in those on MF (-1.5%) and HF (-5.8%). Patients on phase I showed an increase in HDL-C of 9.0% (NS), while those on phase II diet had a 3.6% increase (NS) in HDL-C. TC/HDL-C increased (9.8%) only in patients following the high-fat diets (NS). Patients on MF had a 5.3% (NS) reduction in TC/HDL-C, while those on LF had significant reductions on the phase I ( -45.8%; p=0.0001) diet and phase II diet (-34.7%; p=0.0001). TG levels increased on both the MF (1.0%) and HF (5.5%) diets, although neither was statistically significant. People following the phase I and II diets showed reductions of 37.3% and 36.9%, respectively. Ho levels increased by 9.7% when people followed the MF diet and by 12.4% when they followed the HF diet. Patients following the phase I and phase II diets showed reductions of 13.6% and 14.6%, respectively. Only those following phase II diets showed a tendency toward significant improvement (p=0.061). Lp(a) levels increased by 4.7% following the MF (NS) diet and by 31.0% (NS) on the HF diet. Patients following phase I showed a 7.4% (NS) reduction and a 10.8% reduction (NS) following phase II. Fibrinogen levels increased only in individuals following HF diets (11.9%), while patients following MF (-0.6%), phase I (-11.0%), and phase II (-6.3%) diets showed nonsignificant reductions in fibrinogen. Patients on MF demonstrated nonsignificant reductions in weight, LDL-C, TC, HDL-C, TC/HDL-C ratios, and fibrinogen and nonsignificant increases in TGs, Lp(a), and homocysteine. There was significant weight loss in patients on phase I and II and HF diets after 1 year. Reductions in TC, LDL-C, TGs, and TC/HDL ratios were significant only in patients either following a LF diet or a MF, calorically reduced diet. Only patients following HF diets showed a worsening of each cardiovascular disease risk factor (LDL-C, TG, TC, HDL-C, TC/HDL ratio, Ho, Lp(a), and fibrinogen), despite achieving statistically significant weight loss. Copyright 2002 CHF, Inc.

KSC-08pd1556

NASA Image and Video Library

2008-05-31

CAPE CANAVERAL, Fla. -- Space shuttle Discovery is silhouetted against the clear blue Florida sky as it hurtles toward space on its STS-124 mission to the International Space Station. Beneath the main engine nozzles can be seen the blue cones of light, the shock or mach diamonds that are a formation of shock waves in the exhaust plume of an aerospace propulsion system. Liftoff was on time at 5:02 p.m. EDT. Discovery is making its 35th flight. The STS-124 mission is the 26th in the assembly of the space station. It is the second of three flights launching components to complete the Japan Aerospace Exploration Agency's Kibo laboratory. The shuttle crew will install Kibo's large Japanese Pressurized Module and its remote manipulator system, or RMS. The 14-day flight includes three spacewalks. Photo credit: NASA/Jerry Cannon, George Roberts

Preclinical evaluation of (99m)Tc labeled chondroitin sulfate for monitoring of cartilage degeneration in osteoarthritis.

PubMed

Sobal, Grazyna; Velusamy, Kavitha; Kosik, Siegfried; Menzel, Johannes; Hacker, Marcus; Pagitz, Maximilian

2016-06-01

In previous in-vitro and ex-vivo studies we proved the specific uptake of (99m)Tc radiolabeled chondroitin sulfate (CS) in human articular cartilage. As a logical next step for the clinical use for imaging osteoarthritis we investigated in-vivo uptake of (99m)TcCS in dogs. The radiolabeling of CS Condrosulf (IBSA, Lugano, Switzerland) was performed using 25mg of CS and 20-40MBq/kg body weight of (99m)Tc by means of the tin method. In-vivo uptake of (99m)TcCS was evaluated in dogs (n=12, castrated males, 4-9years, with 15-51kg body weight). 6 healthy dogs served as controls and 6 with clinical and radiological signs of osteoarthritis in the carpal, elbow, and tarsal joint were examined. The tracer was i.v. injected into the external cephalic vein. The uptake was monitored after 2, 4, 6 and 24h in healthy and osteoarthritic dogs using a planar gamma camera by regional planar or whole body ventral and dorsal acquisition. For whole body scintigraphy animals were under general anesthesia, for planar under sedation only. In healthy control dogs we did not detect any specific uptake of (99m)TcCS in the cartilage. In contrast, in the diseased dogs suffering from osteoarthritis a significant, specific, persistent uptake between 4 and 6h in tarsal, carpal and cubital joints was documented. Median target (joint) to background (mid antebrachium) ratio (T/B) in the OA joints after 4, 6, and 24h was significantly higher than in healthy controls. Target to background ratio using soft tissue as a background (T/S) a similar significantly higher than in healthy controls. In all osteoarthritic joints we found a significant positive correlation (r=0.8, n=20) between grade of disease (I-III) and T/B. When matching radiographic (X ray) changes in osteoarthritic joints (grade II and III) we found also a maximal uptake of (99m)TcCS at the specific anatomical site of highest cartilage degeneration. None of the dogs experienced any side effects. These results suggest that (99m)TcCS might become a promising diagnostic tool for imaging osteoarthritis. More extensive and detailed examinations are required, however, before extending this methodology for application in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of source batch S{sub K} dispersion on dosimetry for prostate cancer treatment with permanent implants

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

Nuñez-Cumplido, E., E-mail: ejnc-mccg@hotmail.com; Hernandez-Armas, J.; Perez-Calatayud, J.

2015-08-15

Purpose: In clinical practice, specific air kerma strength (S{sub K}) value is used in treatment planning system (TPS) permanent brachytherapy implant calculations with {sup 125}I and {sup 103}Pd sources; in fact, commercial TPS provide only one S{sub K} input value for all implanted sources and the certified shipment average is typically used. However, the value for S{sub K} is dispersed: this dispersion is not only due to the manufacturing process and variation between different source batches but also due to the classification of sources into different classes according to their S{sub K} values. The purpose of this work is tomore » examine the impact of S{sub K} dispersion on typical implant parameters that are used to evaluate the dose volume histogram (DVH) for both planning target volume (PTV) and organs at risk (OARs). Methods: The authors have developed a new algorithm to compute dose distributions with different S{sub K} values for each source. Three different prostate volumes (20, 30, and 40 cm{sup 3}) were considered and two typical commercial sources of different radionuclides were used. Using a conventional TPS, clinically accepted calculations were made for {sup 125}I sources; for the palladium, typical implants were simulated. To assess the many different possible S{sub K} values for each source belonging to a class, the authors assigned an S{sub K} value to each source in a randomized process 1000 times for each source and volume. All the dose distributions generated for each set of simulations were assessed through the DVH distributions comparing with dose distributions obtained using a uniform S{sub K} value for all the implanted sources. The authors analyzed several dose coverage (V{sub 100} and D{sub 90}) and overdosage parameters for prostate and PTV and also the limiting and overdosage parameters for OARs, urethra and rectum. Results: The parameters analyzed followed a Gaussian distribution for the entire set of computed dosimetries. PTV and prostate V{sub 100} and D{sub 90} variations ranged between 0.2% and 1.78% for both sources. Variations for the overdosage parameters V{sub 150} and V{sub 200} compared to dose coverage parameters were observed and, in general, variations were larger for parameters related to {sup 125}I sources than {sup 103}Pd sources. For OAR dosimetry, variations with respect to the reference D{sub 0.1cm{sup 3}} were observed for rectum values, ranging from 2% to 3%, compared with urethra values, which ranged from 1% to 2%. Conclusions: Dose coverage for prostate and PTV was practically unaffected by S{sub K} dispersion, as was the maximum dose deposited in the urethra due to the implant technique geometry. However, the authors observed larger variations for the PTV V{sub 150}, rectum V{sub 100}, and rectum D{sub 0.1cm{sup 3}} values. The variations in rectum parameters were caused by the specific location of sources with S{sub K} value that differed from the average in the vicinity. Finally, on comparing the two sources, variations were larger for {sup 125}I than for {sup 103}Pd. This is because for {sup 103}Pd, a greater number of sources were used to obtain a valid dose distribution than for {sup 125}I, resulting in a lower variation for each S{sub K} value for each source (because the variations become averaged out statistically speaking)« less

PD-L2 expression in colorectal cancer: Independent prognostic effect and targetability by deglycosylation.

PubMed

Wang, Huanbin; Yao, Han; Li, Chushu; Liang, Lunxi; Zhang, Yao; Shi, Hubing; Zhou, Chongzhi; Chen, Yingxuan; Fang, Jing-Yuan; Xu, Jie

2017-01-01

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46.3 vs 69.1 mo; p = 0.0004). The association remained significant in multivariate COX regression analysis (hazard ratio = 2.778, 95% confidence interval [CI] = 1.668-4.627; p < 0.0001). In the validation CRC data set, significant association between PD-L2 overexpression and poor survival was supported by the univariate analysis (27.1 vs. 88.9 mo; p = 0.0002) and multivariate model (hazard ratio = 7.09, 95%CI 1.78-28.16; p = 0.005). Western Blot revealed strong induction of PD-L2 expression by interferon-γ (IFNγ) in CRC cells, and the mRNA levels of both genes were significantly correlated in CRC tissue samples. Suppression of glycosylation with tunicamycin caused a shift in molecular weight and significant decrease in the expression of PD-L2 protein. In conclusion, PD-L2 overexpression in CRC cells, under the regulation by IFNγ and glycosylation, associates with poor survival of patients with colorectal cancer. These findings highlight PD-L2 as a promising therapeutic target in CRC and suggest potential routes to control PD-L2 expression in CRC cells.

PD-L2 expression in colorectal cancer: Independent prognostic effect and targetability by deglycosylation

PubMed Central

Wang, Huanbin; Yao, Han; Li, Chushu; Liang, Lunxi; Zhang, Yao; Shi, Hubing; Zhou, Chongzhi; Chen, Yingxuan; Fang, Jing-Yuan

2017-01-01

ABSTRACT Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46.3 vs 69.1 mo; p = 0.0004). The association remained significant in multivariate COX regression analysis (hazard ratio = 2.778, 95% confidence interval [CI] = 1.668–4.627; p < 0.0001). In the validation CRC data set, significant association between PD-L2 overexpression and poor survival was supported by the univariate analysis (27.1 vs. 88.9 mo; p = 0.0002) and multivariate model (hazard ratio = 7.09, 95%CI 1.78–28.16; p = 0.005). Western Blot revealed strong induction of PD-L2 expression by interferon-γ (IFNγ) in CRC cells, and the mRNA levels of both genes were significantly correlated in CRC tissue samples. Suppression of glycosylation with tunicamycin caused a shift in molecular weight and significant decrease in the expression of PD-L2 protein. In conclusion, PD-L2 overexpression in CRC cells, under the regulation by IFNγ and glycosylation, associates with poor survival of patients with colorectal cancer. These findings highlight PD-L2 as a promising therapeutic target in CRC and suggest potential routes to control PD-L2 expression in CRC cells. PMID:28811964

Calbindin-D(28k) controls [Ca(2+)](i) and insulin release. Evidence obtained from calbindin-d(28k) knockout mice and beta cell lines

NASA Technical Reports Server (NTRS)

Sooy, K.; Schermerhorn, T.; Noda, M.; Surana, M.; Rhoten, W. B.; Meyer, M.; Fleischer, N.; Sharp, G. W.; Christakos, S.

1999-01-01

The role of the calcium-binding protein, calbindin-D(28k) in potassium/depolarization-stimulated increases in the cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and insulin release was investigated in pancreatic islets from calbindin-D(28k) nullmutant mice (knockouts; KO) or wild type mice and beta cell lines stably transfected and overexpressing calbindin. Using single islets from KO mice and stimulation with 45 mM KCl, the peak of [Ca(2+)](i) was 3.5-fold greater in islets from KO mice compared with wild type islets (p < 0.01) and [Ca(2+)](i) remained higher during the plateau phase. In addition to the increase in [Ca(2+)](i) in response to KCl there was also a significant increase in insulin release in islets isolated from KO mice. Evidence for modulation by calbindin of [Ca(2+)](i) and insulin release was also noted using beta cell lines. Rat calbindin was stably expressed in betaTC-3 and betaHC-13 cells. In response to depolarizing concentrations of K(+), insulin release was decreased by 45-47% in calbindin expressing betaTC cells and was decreased by 70-80% in calbindin expressing betaHC cells compared with insulin release from vector transfected betaTC or betaHC cells (p < 0.01). In addition, the K(+)-stimulated intracellular calcium peak was markedly inhibited in calbindin expressing betaHC cells compared with vector transfected cells (225 nM versus 1,100 nM, respectively). Buffering of the depolarization-induced rise in [Ca(2+)](i) was also observed in calbindin expressing betaTC cells. In summary, our findings, using both isolated islets from calbindin-D(28k) KO mice and beta cell lines, establish a role for calbindin in the modulation of depolarization-stimulated insulin release and suggest that calbindin can control the rate of insulin release via regulation of [Ca(2+)](i).

Macronutrients intake and risk of Parkinson's disease: A meta-analysis.

PubMed

Wang, Aimin; Lin, Yan; Wu, Yili; Zhang, Dongfeng

2015-05-01

We carried out a meta-analysis to summarize the evidence from published studies on macronutrients intake and risk of Parkinson's disease (PD). Pertinent studies were identified by a search of PubMed and Embase. Study-specific effect was combined with the random-effect model. The dose-response relationship was assessed by the restricted cubic spline. For highest versus lowest level of intake, the relative risk (RR) of PD was 1.13 (95% CI 0.88-1.44) for protein (7 articles including 1570 PD cases among 357,827 subjects), RR 1.24 (95% CI 1.05-1.48) for carbohydrate (8 articles including 1482 PD cases among 232,869 subjects), RR 0.88 (95% CI 0.74-1.06) for fat (12 articles including 2936 PD cases among 374,124 subjects), RR 0.97 (95% CI 0.75-1.26) for cholesterol (6 articles including 1713 PD cases among 170,058 subjects) and 1.39 (95% CI 1.01-1.92) for energy (8 articles including 1553 PD cases among 170,317 subjects), respectively. Among prospective studies adjusting for smoking and coffee/caffeine, no associations were found between PD risk and intake of protein (RR 1.02, 95% CI 0.80-1.30), carbohydrate (RR 1.11, 95% CI 0.86-1.43), fat (RR 0.90, 95% CI 0.70-1.16), cholesterol (RR 0.89, 95% CI 0.74-1.09) and energy (RR 0.97, 95% CI 0.93-1.02); however, polyunsaturated fatty acid (RR 0.78, 95% CI 0.64-0.96) was inversely associated with PD risk. Limited data showed a linear dose-response relationship between the aforementioned macronutrients and PD risk. Dietary intake of protein, carbohydrate, cholesterol and energy might be not independently associated with PD risk. Higher intake of polyunsaturated fatty acid might be inversely associated with PD risk. Confounding by smoking and coffee/caffeine should be considered regarding the association between fat intake and PD risk in further studies. © 2014 Japan Geriatrics Society.

Application of a palladium hexacyanoferrate film-modified aluminum electrode to electrocatalytic oxidation of hydrazine.

PubMed

Razmi, Habib; Azadbakht, Azadeh; Sadr, Moayad Hossaini

2005-11-01

A palladium hexacyanoferrate (PdHCF) film as an electrocatalytic material was obtained at an aluminum (Al) electrode by a simple electroless dipping method. The modified Al electrode demonstrated a well-behaved redox couple due to the redox reaction of the PdHCF film. The PdHCF film showed an excellent electrocatalytic activity toward the oxidation of hydrazine. The electrocatalytic oxidation of hydrazine was studied by cyclic voltammetry and rotating disk electrode voltammetry techniques. A calibration graph obtained for the hydrazine consisted of two segments (localized at concentration ranges 0.39-10 and 20-75 mM). The rate constant k and transfer coefficient alpha for the catalytic reaction and the diffusion coefficient of hydrazine in the solution D, were found to be 3.11 x 10(3) M(-1) s(-1), 0.52 and 8.03 x 10(-6) cm2 s(-1) respectively. The modified electrode was used to amperometric determination of hydrazine in photographic developer. The interference of ascorbic acid and thiosulfate were investigated and greatly reduced using a thin film of Nafion on the modified electrode. The modified electrode indicated reproducible behavior and a high level of stability during electrochemical experiments, making it particularly suitable for analytical purposes.

Untangling the transmission dynamics of primary and secondary vectors of Trypanosoma cruzi in Colombia: parasite infection, feeding sources and discrete typing units.

PubMed

Hernández, Carolina; Salazar, Camilo; Brochero, Helena; Teherán, Aníbal; Buitrago, Luz Stella; Vera, Mauricio; Soto, Hugo; Florez-Rivadeneira, Zulibeth; Ardila, Sussane; Parra-Henao, Gabriel; Ramírez, Juan David

2016-12-01

Trypanosoma cruzi is the causative agent of Chagas disease. Due to its genetic diversity has been classified into six Discrete Typing Units (DTUs) in association with transmission cycles. In Colombia, natural T. cruzi infection has been detected in 15 triatomine species. There is scarce information regarding the infection rates, DTUs and feeding preferences of secondary vectors. Therefore, the aim of this study was to determine T. cruzi infection rates, parasite DTU, ecotopes, insect stages, geographical location and bug feeding preferences across six different triatomine species. A total of 245 insects were collected in seven departments of Colombia. We conducted molecular detection and genotyping of T. cruzi with subsequent identification of food sources. The frequency of infection, DTUs, TcI genotypes and feeding sources were plotted across the six species studied. A logistic regression model risk was estimated with insects positive for T. cruzi according to demographic and eco-epidemiological characteristics. We collected 85 specimens of Panstrongylus geniculatus, 77 Rhodnius prolixus, 37 R. pallescens, 34 Triatoma maculata, 8 R. pictipes and 4 T. dimidiata. The overall T. cruzi infection rate was 61.2% and presented statistical associations with the departments Meta (OR: 2.65; 95% CI: 1.69-4.17) and Guajira (OR: 2.13; 95% CI: 1.16-3.94); peridomestic ecotope (OR: 2.52: 95% CI: 1.62-3.93); the vector species P. geniculatus (OR: 2.40; 95% CI: 1.51-3.82) and T. maculata (OR: 2.09; 95% CI: 1.02-4.29); females (OR: 2.05; 95% CI: 1.39-3.04) and feeding on opossum (OR: 3.15; 95% CI: 1.85-11.69) and human blood (OR: 1.55; 95% CI: 1.07-2.24). Regarding the DTUs, we observed TcI (67.3%), TcII (6.7%), TcIII (8.7%), TcIV (4.0%) and TcV (6.0%). Across the samples typed as TcI, we detected TcIDom (19%) and sylvatic TcI (75%). The frequencies of feeding sources were 59.4% (human blood); 11.2% (hen); 9.6% (bat); 5.6% (opossum); 5.1% (mouse); 4.1% (dog); 3.0% (rodent); 1.0% (armadillo); and 1.0% (cow). New scenarios of T. cruzi transmission caused by secondary and sylvatic vectors are considered. The findings of sylvatic DTUs from bugs collected in domestic and peridomestic ecotopes confirms the emerging transmission scenarios in Colombia.

The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing.

PubMed

Makeyev, Eugene V; Zhang, Jiangwen; Carrasco, Monica A; Maniatis, Tom

2007-08-03

Both microRNAs and alternative pre-mRNA splicing have been implicated in the development of the nervous system (NS), but functional interactions between these two pathways are poorly understood. We demonstrate that the neuron-specific microRNA miR-124 directly targets PTBP1 (PTB/hnRNP I) mRNA, which encodes a global repressor of alternative pre-mRNA splicing in nonneuronal cells. Among the targets of PTBP1 is a critical cassette exon in the pre-mRNA of PTBP2 (nPTB/brPTB/PTBLP), an NS-enriched PTBP1 homolog. When this exon is skipped, PTBP2 mRNA is subject to nonsense-mediated decay (NMD). During neuronal differentiation, miR-124 reduces PTBP1 levels, leading to the accumulation of correctly spliced PTBP2 mRNA and a dramatic increase in PTBP2 protein. These events culminate in the transition from non-NS to NS-specific alternative splicing patterns. We also present evidence that miR-124 plays a key role in the differentiation of progenitor cells to mature neurons. Thus, miR-124 promotes NS development, at least in part by regulating an intricate network of NS-specific alternative splicing.

Phase I Inspection Report. National Dam Safety Program, Boonton Dam and Parsippany Dike, Morris County, New Jersey.

DTIC Science & Technology

1978-05-01

13 to >, ft 8« 0*0 o SH s flj r u J5H to TJ 50 CD <u g 4-J 4-> S cd cö § 3> _ *-s Pu CO 0) o ill X! £4 co •34* 2 ff-o . I <U I 4...er t kJ A *- «sj »n jeM«r IS- z p* ** tC f- c^ — •; n — c — O «4 o o tD • • »* **. «« w4 II « ?iTc ^ •* «o rw 4T o*> rv, P* or or...A OX M K> if- CT- tD w m t* ft* O O • r"> X o .r*» I IT -* CT» K- *? Of • «O • » — ro -4 O O» • N X MK fM

Asymmetrical A-Frame Triplatinum Clusters Bridged by Small Organic Molecules and Bis((diphenylphosphino)methyl)phenylphosphine.

PubMed

Tanase, Tomoaki; Ukaji, Hirokazu; Igoshi, Toshiaki; Yamamoto, Yasuhiro

1996-07-03

Reactions of the linear triplatinum complex [Pt(3)(&mgr;-dpmp)(2)(XylNC)(2)](2+) (3) with small organic molecules led to formation of asymmetrical A-frame triplatinum complexes with an additional bridge across one of the metal-metal bonds, where dpmp is bis((diphenylphosphino)methyl)phenylphosphine. Reaction of complex 3 with electron deficient alkynes (R(1)C&tbd1;CR(2): R(1) = R(2) = CO(2)Me; R(1) = H, R(2) = CO(2)Me; R(1) = R(2) = CO(2)Et) afforded a new series of triplatinum clusters formulated as [Pt(3)(&mgr;-dpmp)(2)(&mgr;-R(1)CCR(2))(XylNC)(2)](PF(6))(2) (5a, R(1) = R(2) = CO(2)Me; 5b, R(1) = H, R(2) = CO(2)Me; 5c, R(1) = R(2) = CO(2)Et) in good yields. The complex cation of 5b was characterized by X-ray crystallography to have an asymmetrical A-frame structure comprising three Pt atoms bridged by two dpmp ligands, in which an acetylene molecule was inserted into one of the Pt-Pt bonds (triclinic, P&onemacr;, a = 19.507(3) Å, b = 20.327(4) Å, c = 14.499(4) Å, alpha = 107.69(2) degrees, beta = 102.08(2) degrees, gamma = 71.30(1) degrees, V = 5148 Å(3), Z = 2, R = 0.070, and R(w) = 0.084). The Pt-Pt bond length is 2.718(1) Å and the Pt.Pt nonbonded distance is 3.582(1) Å. Treatment of 3 with an excess of HBF(4).Et(2)O gave the asymmetrical cluster [Pt(3)(&mgr;-dpmp)(2)(&mgr;-H)(XylNC)(2)](BF(4))(3).CH(2)Cl(2) (6.CH(2)Cl(2)), in 61% yield, and a similar reaction with p-NO(2)C(6)H(4)NC led to the formation of [Pt(3)(&mgr;-dpmp)(2)(&mgr;-R(3)NC)(XylNC)(2)](PF(6))(2).CH(2)Cl(2) (7.CH(2)Cl(2)) in 94% yield (R(3) = p-NO(2)C(6)H(4)). Complexes 6 and 7 are assumed to have a single atom-bridged, asymmetrical A-frame structures. Reaction of the complex syn-[Pt(2)(&mgr;-dpmp)(2)(XylNC)(2)](2+) (1) with [MCl(2)(cod)] (M = Pt, Pd) gave the dimer-monomer combined trinuclear cluster [Pt(2)MCl(2)(&mgr;-dpmp)(2)(XylNC)(2)](PF(6))(2) (8a, M = Pt, 89%; 8b, M = Pd, 55%). The structure of 8a was determined by X-ray crystallography to be comprised of a metal-metal-bonded diplatinum core and a monomeric platinum center bridged by two dpmp ligands with a face-to-face arrangement (triclinic, P&onemacr;, a = 18.082(7) Å, b = 19.765(6) Å, c = 15.662(4) Å, alpha = 98.51(2) degrees, beta = 94.24(3) degrees, gamma = 109.82(2) degrees, V = 5161 Å(3), Z = 2, R = 0.069, and R(w) = 0.080). The Pt-Pt bond length is 2.681(2) Å and the Pt.Pt nonbonded distance is 3.219(2) Å. The heteronuclear complex 8b was transformed to an A-frame trinuclear cluster, [Pt(2)PdCl(&mgr;-Cl)(&mgr;-dpmp)(2)(XylNC)](PF(6))(2) (9), which was characterized by X-ray crystallography (monoclinic, C2/c, a = 33.750(9) Å, b = 28.289(9) Å, c = 23.845(8) Å, beta = 118.19(4) degrees, V = 20066 Å(3), Z = 8, R = 0.082, and R(w) = 0.077). The diplatinum unit (Pt-Pt = 2.606(2) Å) is connected to the mononuclear Pd center by a chloride bridge (Pt.Pd = 3.103(3) Å, Pt-Cl-Pd = 79.6(3) degrees ).

Evaluation of ⁹⁹(m)Tc-labeled antibiotics for infection detection.

PubMed

Lambrecht, Fatma Yurt

2011-01-01

One of the fields of research in nuclear medicine is the development of new radiopharmaceuticals for imaging infection and inflammation in humans. For this development, several antimicrobial peptides, antibiotics, antibiotic peptide and chemotactic peptides, etc., have been radiolabeled with different radionuclides (⁶⁷Ga, ⁹⁹(m)Tc, ¹¹¹In, ¹⁸F, ¹³¹I, etc.) and their imaging potentials studied. Actually, it is very important to distinguish between infection and inflammation. In this respect, radiolabeled antibiotics have advantages because many of the properties of the ideal infection-specific agent through antibiotics localizes in infection site. In this review, only ⁹⁹(m)Tc-labeled antibiotics are evaluated and discussed.

Cobalt Fischer-Tropsch catalysts having improved selectivity

DOEpatents

Miller, James G.; Rabo, Jule A.

1989-01-01

The promoter(s) Mn oxide or Mn oxide and Zr oxide are added to a cobalt Fischer-Tropsch catalyst combined with the molecular sieve TC-103 or TC-123 such that the resultant catalyst demonstrates improved product selectivity, stability and catalyst life. The improved selectivity is evidenced by lower methane production, higher C5+ yield and increased olefin production.

Bombesin receptors and transplanted stem cells in rat brain: High-resolution scan with 99mTc BN1.1

NASA Astrophysics Data System (ADS)

Scopinaro, F.; Paschali, E.; Di Santo, G.; Antonellis, T.; Massari, R.; Trotta, C.; Gourni, H.; Bouziotis, P.; David, V.; Soluri, A.; Varvarigou, A. D.

2006-12-01

The aim of this work is to detect the presence of transplanted stem cells (TSC) in rat brain with high-resolution (HR) scintigraphy and labelled bombesin (BN). BN is a morphogen for Central Nervous System (CNS) as well as for other organs: CNS-oriented TSC over-express BN Receptors (BNR). BN is also a neurotransmitter and modulates several functions of CNS. 99mTc labelled BN-like peptide scan of CNS is the ideal method to detect growing TSC once knowing normal distribution of BNRs in CNS. HR Planar and single photon emission computerized tomography (SPECT) images of rat brain were performed with new HR detectors (Li-tech, Italy). Pertechnetate, 99mTc HMPAO and the new 99mTc BN1.1 (patented) were i.v. administered in five rats. HR SPECT of 99mTc BN1.1 detected olfactory tract, fronto-lateral cortex, cerebellum, basal ganglia and amygdale. Results of SPECT were confirmed by bio-distribution study performed after autopsy of three of the five rats. The remaining two rats underwent cerebral lesions followed by transplant of TSC. Three months later, HR scintigraphy was repeated and showed images completely different from previous basal study, with hot spot of 99mTc BN1.1 corresponding to the site of TSC transplant. Immuno-histochemistry confirmed the presence of viable TSC. Not only 99mTc BN1.1 HR scan showed viability of transplanted TSC but also the "background brain" was the still now unknown map of BNR in mammalian brain.

A novel approach to infection imaging using a synthetic Tc-99m-labeled leukotactic peptide

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

Som, P.; Oster, Z.H.; Sharma, S.

1996-05-01

RMT1, a synthetic peptide binding to PMN and macrophage receptors was labeled with Tc-99m and investigated as a potential imaging agent for abscess and inflammation. Experimental abscesses were induced in rabbits and dogs by turpentine and E.coli injection. After injection of Tc-99m-RMT1 two and twelve day old abscesses were visualized within 20 min. In initial studies, a dose of 30 {mu}g of peptide/3 mCi was used. This amount was subsequently reduced to 1.5 {mu}g peptide with same amount of Tc-99m yielding similar imaging results. Technetium-99m-IgG and Tc-99m-MAG-3 were used as positive and negative controls, respectively. After injection of IgG abscessesmore » were visualized but activity in blood was always higher than in abscess. When using Tc-99m RMT1 rapid abscess visualization and faster blood clearance was observed. The accumulation of RMT1 was monophasic, i.e., following the initial visualization, activity continued to build up continuously for 1{1/2} hr. Tc-99m-MAG3 accumulated initially in abscess, but activity washed out. In dogs, RMT1 blood clearance showed three components: a fast component with t{1/2}=1.9 min, 73%, intermediate t{1/2}=22 min, 24.5% and slow component, t{1/2}=115, 9.5% with 3 hours cumulative urine excretion of 40-51%. RMT1 appears to be more advantageous than currently available methods because of rapidity of imaging, simpler preparation before injection and will probably be less expensive and time consuming compared to labeled WBC. These results indicate that clinical experiments are warranted.« less

Association of VDR gene polymorphisms with risk of relapsing-remitting multiple sclerosis in an Iranian Kurdish population.

PubMed

Abdollahzadeh, Rasoul; Moradi Pordanjani, Parisa; Rahmani, Farideh; Mashayekhi, Fatemeh; Azarnezhad, Asaad; Mansoori, Yaser

2018-06-01

The purpose of this study was to evaluate the association of VDR Apa-I, Bsm-I, Fok-I, Taq-I single nucleotide polymorphisms (SNPs) with multiple sclerosis (MS) risk in an Iranian Kurdish population. A population including of 118 patients and 124 healthy matched controls were recruited to the study. Genotyping of the SNPs was accomplished using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequency of allele T of Fok-I (P = 0.003) and allele C of Taq-I (P = 0.0003) was significantly different between case and control subjects and showed significant association with risk of MS (OR = 1.84, 95% CI = 1.23-2.76; OR = 1.98, 95% CI = 1.36-2.87, respectively). CT genotype (OR = 1.7, 95% CI = 1.05-2.99) of Fok-I and CC genotype (OR = 2.18, 95% CI = 1.05-4.52) of Taq-I showed a predisposing effect. Combined TT+TC vs. CC for Fok-I (OR = 2.15, 95% = CI 1.29-3.60) and combined CC+TC vs. TT for Taq-I (OR = 2.58, 95% CI 1.51-4.40) were susceptibility genotypes for MS. Apa-I and Bsm-I were not significantly associated with risk of MS (OR < 1, P > 0.05) and any genotypes in any genetic models were not significantly different between cases and controls (P > 0.05). As a result, Fok-I and Taq-I showed significant association with risk of MS, while Apa-I and Bsm-I were not observed to be related to the risk of the disease in this population.

Imaging Lung Clearance of Radiolabeled Tumor Cells to Study Mice with Normal, Activated or Depleted Natural Killer (NK) Cells

NASA Astrophysics Data System (ADS)

Kulkarni, P. V.; Bennett, M.; Constantinescu, A.; Arora, V.; Viguet, M.; Antich, P.; Parkey, R. W.; Mathews, D.; Mason, R. P.; Oz, O. K.

2003-08-01

Lung clearance of 51CR and 125I iododeoxyuridine (IUDR) labeled cancer cells assess NK cell activity. It is desirable to develop noninvasive imaging technique to assess NK activity in mice. We labeled target YAC-1 tumor cells with 125I, 111In, 99mTc, or 67Ga and injected I.V. into three groups of BALB/c mice. Animals were treated with medium (group I), 300mg/kg cyclophosmamide (CY) to kill NK cell (group II), or anti-LY49C/1) (ab')2 mAb to augment NK function (group III). Lungs were removed 15 min or 2 h later for tissue counting. Control and treated mice were imaged every 5 min with a scintillating camera for 1 h after 15 min of infusion of the 111In labeled cells. Lung clearance increased after 15 min (lodging: 60-80%) and (2 h retention: 3-7%). Similar results were obtained with all the isotopes studied. Images distinguished the control and treated mice for lung activity. Cells labeled with 111In, 99mTc or 67Ga are cleared similar to those labeled with 51Cr or 125I. NK cell destruction of tumor cells may be assessed by noninvasive imaging method either by SPECT (99mTc, 111In, 67Ga) or by PET (68Ga).

Comparison of Exposures Among Arab American and Non-Hispanic White Female Thyroid Cancer Cases in Metropolitan Detroit

PubMed Central

Peterson, L.; Soliman, A.; Ruterbusch, J. J.; Smith, N.

2013-01-01

Arab American (ArA) women may be at greater risk for thyroid cancer (TC) than White women. This case-case comparison explored differences in known and proposed risk factors of TC among ArA and non-Hispanic White (NHW) female TC cases in metropolitan Detroit. Cases of invasive TC identified from a population-based registry responded to a telephone survey regarding potential TC risk factors. Thirty ArA women (response rate 52%) and 70 NHW women (67%) participated. NHW women reported significantly more prior thyroid disease (TD), family history of TD, hormone use, cumulative years of hormone use, cigarette and alcohol consumption. In adjusted logistic regression analysis, ArA women had significantly higher odds of exposure to dental x-rays (OR = 3.48, CI 1.01–12.00) and medical radiation (OR = 13.58, CI 1.49–124.04) than NHW women. Risk factors for TC may differ among ArA women and their NHW counterparts. PMID:21647624

Comparison of exposures among Arab American and non-Hispanic White female thyroid cancer cases in metropolitan Detroit.

PubMed

Peterson, L; Soliman, A; Ruterbusch, J J; Smith, N; Schwartz, K

2011-12-01

Arab American (ArA) women may be at greater risk for thyroid cancer (TC) than White women. This case-case comparison explored differences in known and proposed risk factors of TC among ArA and non-Hispanic White (NHW) female TC cases in metropolitan Detroit. Cases of invasive TC identified from a population-based registry responded to a telephone survey regarding potential TC risk factors. Thirty ArA women (response rate 52%) and 70 NHW women (67%) participated. NHW women reported significantly more prior thyroid disease (TD), family history of TD, hormone use, cumulative years of hormone use, cigarette and alcohol consumption. In adjusted logistic regression analysis, ArA women had significantly higher odds of exposure to dental x-rays (OR = 3.48, CI 1.01-12.00) and medical radiation (OR = 13.58, CI 1.49-124.04) than NHW women. Risk factors for TC may differ among ArA women and their NHW counterparts.

Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

NASA Astrophysics Data System (ADS)

Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

2016-02-01

Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

Identification, characterization, and quantitation of soluble HLA antigens in the circulation and peritoneal dialysate of renal patients.

PubMed Central

Gelder, F B; McDonald, J C; Landreneau, M D; McMillan, R M; Aultman, D F

1991-01-01

Human lymphocyte antigen (HLA) class I and class II antigens and beta 2 microglobulin (B2M) were identified in peritoneal dialysate (PD) and serum from patients with end-stage renal disease (ESRD) using monoclonal antibodies in an enzyme-linked immunoassay. The HLA class I and class II antigens each exhibited approximate molecular weights of 50,000 to 60,000 daltons by chromatography on Sepharose CL 6B. Class I antigens in serum and PD fluid were associated with B2M. Free B2M (Mr 11,500) also was detected in both sera and PD fluids. Unlike class I antigens, class II antigens were not found to have attached B2M. Class I and class II antigens eluted from 2-diethylaminoethanol ion exchange gradient columns at 0.07 mol/L (molar) phosphate buffer pH 7.2 and migrated with alpha 2-beta 1 mobility in agarose electrophoresis. Class I antigens were purified from ESRD patients' PD fluid by solid-phase immunoaffinity chromatography. Enzyme-linked immunoassay demonstrated that this purified protein was composed of a class I heavy chain and B2M. Class I allospecificity was confirmed by neutralization on known HLA typing antisera in a microcytotoxicity assay. Soluble HLA class I antigen preparations specifically inhibited blast transformation of responder lymphocytes in mixed lymphocyte culture reactions. Inhibition was dose dependent and ranged from 0% to 95%. The presence of soluble HLA antigens in body fluids may play an important part in the immunologic tolerance to self. This study demonstrates a ready source of large quantities of soluble HLA for detailed analysis. Images Fig. 1. PMID:2039290

The helical domain of the EcoR124I motor subunit participates in ATPase activity and dsDNA translocation

PubMed Central

Shamayeva, Katsiaryna; Guzanova, Alena; Řeha, David; Csefalvay, Eva; Carey, Jannette; Weiserova, Marie

2017-01-01

Type I restriction-modification enzymes are multisubunit, multifunctional molecular machines that recognize specific DNA target sequences, and their multisubunit organization underlies their multifunctionality. EcoR124I is the archetype of Type I restriction-modification family IC and is composed of three subunit types: HsdS, HsdM, and HsdR. DNA cleavage and ATP-dependent DNA translocation activities are housed in the distinct domains of the endonuclease/motor subunit HsdR. Because the multiple functions are integrated in this large subunit of 1,038 residues, a large number of interdomain contacts might be expected. The crystal structure of EcoR124I HsdR reveals a surprisingly sparse number of contacts between helicase domain 2 and the C-terminal helical domain that is thought to be involved in assembly with HsdM. Only two potential hydrogen-bonding contacts are found in a very small contact region. In the present work, the relevance of these two potential hydrogen-bonding interactions for the multiple activities of EcoR124I is evaluated by analysing mutant enzymes using in vivo and in vitro experiments. Molecular dynamics simulations are employed to provide structural interpretation of the functional data. The results indicate that the helical C-terminal domain is involved in the DNA translocation, cleavage, and ATPase activities of HsdR, and a role in controlling those activities is suggested. PMID:28133570

Development of a patient-specific dosimetry estimation system in nuclear medicine examination

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

Lin, H. H.; Dong, S. L.; Yang, H. J.

2011-07-01

The purpose of this study is to develop a patient-specific dosimetry estimation system in nuclear medicine examination using a SimSET-based Monte Carlo code. We added a dose deposition routine to store the deposited energy of the photons during their flights in SimSET and developed a user-friendly interface for reading PET and CT images. Dose calculated on ORNL phantom was used to validate the accuracy of this system. The S values for {sup 99m}Tc, {sup 18}F and {sup 131}I obtained by the system were compared to those from the MCNP4C code and OLINDA. The ratios of S values computed by thismore » system to those obtained with OLINDA for various organs were ranged from 0.93 to 1.18, which are comparable to that obtained from MCNP4C code (0.94 to 1.20). The average ratios of S value were 0.99{+-}0.04, 1.03{+-}0.05, and 1.00{+-}0.07 for isotopes {sup 131}I, {sup 18}F, and {sup 99m}Tc, respectively. The simulation time of SimSET was two times faster than MCNP4C's for various isotopes. A 3D dose calculation was also performed on a patient data set with PET/CT examination using this system. Results from the patient data showed that the estimated S values using this system differed slightly from those of OLINDA for ORNL phantom. In conclusion, this system can generate patient-specific dose distribution and display the isodose curves on top of the anatomic structure through a friendly graphic user interface. It may also provide a useful tool to establish an appropriate dose-reduction strategy to patients in nuclear medicine environments. (authors)« less

[(99)Tc(m)N-NOET dual-phase SPECT in differential diagnosis of benign and malignant lung tumors].

PubMed

Liu, Haiyan; Li, Sijin; Yang, Suyun; Wu, Zhifang

2014-01-01

To investigate the value of (99)Tc(m)N-NOET dual-phase SPECT in differential diagnosis of benign and malignant lung tumors. CT scan, early (20 to 30 min) and delayed (2 h) imaging of NOET SPECT were performed on 61 patients suspected of lung lesions before operation. The results were compared with the pathological findings. All cases were not treated with radiotherapy, chemotherapy or surgery before checks. Moreover, all patients had pathological diagnosis. To determine the value in differential diagnosis of tumors by analyzing the tumor uptake and excretion of (99)Tc(m)N-NOET, and the results were compared with that of CT. The value of early T/N ratio (ER) in the malignant (G1) and benign (G2) groups was 1.25 ± 0.15 and 1.09 ± 0.11 (P < 0.001), respectively, and delayed T/N ratio (DR) was 1.40 ± 0.17 and 1.18 ± 0.21 (P < 0.001). The retention index (RI) of groups G1 was (12.22 ± 6.38)% and group G2 was (8.3 ± 10.91)%, with a non-significant difference between them (P > 0.05). The ER, DR and RI of NOET SPECT in the malignant patients were not significantly correlated with TNM staging, pathological types, tumor diameter, cavity in the lung tumor mass, history of smoking, tumor size and patient gender (P > 0.05). The sensitivity of NOET dual-phase SPECT and CT in the differential diagnosis of benign and malignant lung tumors was 94.1% vs. 90.2%, specificity was 70.0% vs. 80.0% , positive predictive value (PPV) was 94.1% vs. 95.8%, negative predictive value (NPV) was 70.0% vs. 61.5 %, and accuracy was 90.2%. vs. 88.5% (P > 0.05 for all). (99)Tc(m)N- NOET dual-phase SPECT could be used in differential diagnosis of benign and malignant lung tumors, with no significant differences compared with the efficacy of CT imaging. The semiquantitative indexes (ER, DR and RI) of NOET SPECT can also be used in differential diagnosis of benign and malignant lung tumors, and are not significantly correlated with TNM staging, pathological types, tumor diameter, cavity of the lung tumor mass, history of smoking, tumor size and patient gender.

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

Nally, J.V.; Clarke, H.S.; Grecos, G.P.

To assess the effect of CAP on individual kidney function in ..mu..RAS, the authors compared computer assisted 90 second and 15 minute /sup 99m/Tc-DTPA renal flow studies vs /sup 131/I-Hippuran renography with and without CAP. In Group 1 (n=10), angiograms, split function C/sub PAH/, DTPA and Hippuran studies were performed in dogs pre and post ..mu..RAS. Group II animals (n=8) with milder stenosis underwent the same protocol, plus DTPA and Hippuran studies, C/sub PAH/, and C/sub IN/ were performed during CAP (Captopril 1.5 mg/kg bolus and 1.5 mg/min x 60 min.) Recovery DTPA and Hippuran studies (Rec) were performed andmore » were also obtained using nitroprusside (NP) to lower MP to a similar degree as CAP. The authors conclude /sup 99m/Tc-DTPA studies proved superior to Hipurran renography in both Groups I and II. With mild ..mu..RAS, CAP induced a decrease in ipsilateral GFR resulting in striking changes in the /sup 99m/Tc-DTPA curves such that all were now diagnostic of uRAS. These changes appeared specific for CAP and independent of MAP reduction with NP, and /sup 99m/Tc-DTPA renal flow studies with CAP unmask unilateral angiotension II dependent renal hemodynamic changes.« less

Dosimetric effects of seed anisotropy and interseed attenuation for {sup 103}Pd and {sup 125}I prostate implants

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

Chibani, Omar; Williamson, Jeffrey F.; Todor, Dorin

2005-08-15

A Monte Carlo study is carried out to quantify the effects of seed anisotropy and interseed attenuation for {sup 103}Pd and {sup 125}I prostate implants. Two idealized and two real prostate implants are considered. Full Monte Carlo simulation (FMCS) of implants (seeds are physically and simultaneously simulated) is compared with isotropic point-source dose-kernel superposition (PSKS) and line-source dose-kernel superposition (LSKS) methods. For clinical pre- and post-procedure implants, the dose to the different structures (prostate, rectum wall, and urethra) is calculated. The discretized volumes of these structures are reconstructed using transrectal ultrasound contours. Local dose differences (PSKS versus FMCS and LSKSmore » versus FMCS) are investigated. The dose contributions from primary versus scattered photons are calculated separately. For {sup 103}Pd, the average absolute total dose difference between FMCS and PSKS can be as high as 7.4% for the idealized model and 6.1% for the clinical preprocedure implant. Similarly, the total dose difference is lower for the case of {sup 125}I: 4.4% for the idealized model and 4.6% for a clinical post-procedure implant. Average absolute dose differences between LSKS and FMCS are less significant for both seed models: 3 to 3.6% for the idealized models and 2.9 to 3.2% for the clinical plans. Dose differences between PSKS and FMCS are due to the absence of both seed anisotropy and interseed attenuation modeling in the PSKS approach. LSKS accounts for seed anisotropy but not for the interseed effect, leading to systematically overestimated dose values in comparison with the more accurate FMCS method. For both idealized and clinical implants the dose from scattered photons represent less than 1/3 of the total dose. For all studied cases, LSKS prostate DVHs overestimate D{sub 90} by 2 to 5% because of the missing interseed attenuation effect. PSKS and LSKS predictions of V{sub 150} and V{sub 200} are overestimated by up to 9% in comparison with the FMCS results. Finally, effects of seed anisotropy and interseed attenuation must be viewed in the context of other significant sources of dose uncertainty, namely seed orientation, source misplacement, prostate morphological changes and tissue heterogeneity.« less

99mTc-EDDA/HYNIC-Tyr(3)-octreotide for staging and follow-up of patients with neuroendocrine gastro-entero-pancreatic tumors.

PubMed

Gabriel, M; Muehllechner, P; Decristoforo, C; von Guggenberg, E; Kendler, D; Prommegger, R; Profanter, C; Moncayo, R; Virgolini, I

2005-09-01

To evaluate the use of 99mTc-EDDA-hydrazinonicotinyl-Tyr3-octreotide (Tc-TOC) for staging and follow-up of neuroendocrine gastro-entero-pancreatic (GEP) tumors with special focus on the acquisition protocol including single photon emission computed tomography (SPECT). Eighty-eight patients (37 female, 51 male; age range: 16 to 81 years; mean age: 56.3 years) were studied: 42 patients for staging after initial histological confirmation and 46 patients during post-therapy follow-up. An average activity of 400 MBq of the radiopharmaceutical was injected. All tumors originated from neuroendocrine tissue of the gastroenteropancreatic tract. Whole body scintigrams at 4 h postinjection and SPECT of the abdomen were obtained in all patients. Additional planar images of the abdomen were acquired at 2 h after injection in 68 patients. The Tc-TOC scan result was true-positive in 56 patients, true-negative in 17, false-negative in 14, and false-positive in 1 patient. The false-positive finding was caused by a colonic adenoma. Overall, a scan sensitivity of 80% (56/70 patients), specificity of 94.4% (17/18 patients) and accuracy of 82.9% (73/88 patients) were calculated on patient basis. In total, Tc-TOC detected 357 foci in 69 patients. In 7 patients equivocal findings were observed in the bowel at 4 h postinjection without corresponding tracer uptake in the scan 2 h earlier, meaning that these abnormal findings were correctly classified as non-malignant. In addition to planar views, SPECT revealed further 62 lesions. Tc-TOC with one-day, dual-time acquisition protocol is an accurate staging procedure in patients with neuroendocrine GEP tumors. SPECT shows high sensitivity for detection of abdominal lesions, while earlier images improve the reliability of abnormal abdominal findings.

XeCl laser pumped iodine laser using t-C4F9I

NASA Technical Reports Server (NTRS)

Hwang, In Heon; Han, Kwang S.

1989-01-01

An iodine photodissociation laser using t-C4F9I as the active material was pumped by an XeCl laser. An iodine laser output energy of 3 mJ with pulse duration of 25 ns was obtained when the pumping pulse energy was 80 mJ, the iodide pressure was 70 torr, and the reflectance of the output mirror was 85 percent. The high pumping efficiency and low threshold pump power achieved in this experiment are attributable to the high absorption cross section at the pump laser wavelength (308 nm) of the iodide used.

Air-kerma strength determination of a new directional (103)Pd source.

PubMed

Aima, Manik; Reed, Joshua L; DeWerd, Larry A; Culberson, Wesley S

2015-12-01

A new directional (103)Pd planar source array called a CivaSheet™ has been developed by CivaTech Oncology, Inc., for potential use in low-dose-rate (LDR) brachytherapy treatments. The array consists of multiple individual polymer capsules called CivaDots, containing (103)Pd and a gold shield that attenuates the radiation on one side, thus defining a hot and cold side. This novel source requires new methods to establish a source strength metric. The presence of gold material in such close proximity to the active (103)Pd region causes the source spectrum to be significantly different than the energy spectra of seeds normally used in LDR brachytherapy treatments. In this investigation, the authors perform air-kerma strength (S(K)) measurements, develop new correction factors for these measurements based on an experimentally verified energy spectrum, and test the robustness of transferring S(K) to a well-type ionization chamber. S(K) measurements were performed with the variable-aperture free-air chamber (VAFAC) at the University of Wisconsin Medical Radiation Research Center. Subsequent measurements were then performed in a well-type ionization chamber. To realize the quantity S(K) from a directional source with gold material present, new methods and correction factors were considered. Updated correction factors were calculated using the MCNP 6 Monte Carlo code in order to determine S(K) with the presence of gold fluorescent energy lines. In addition to S(K) measurements, a low-energy high-purity germanium (HPGe) detector was used to experimentally verify the calculated spectrum, a sodium iodide (NaI) scintillating counter was used to verify the azimuthal and polar anisotropy, and a well-type ionization chamber was used to test the feasibility of disseminating S(K) values for a directional source within a cylindrically symmetric measurement volume. The UW VAFAC was successfully used to measure the S(K) of four CivaDots with reproducibilities within 0.3%. Monte Carlo methods were used to calculate the UW VAFAC correction factors and the calculated spectrum emitted from a CivaDot was experimentally verified with HPGe detector measurements. The well-type ionization chamber showed minimal variation in response (<1.5%) as a function of source positioning angle, indicating that an American Association of Physicists in Medicine (AAPM) Accredited Dosimetry Calibration Laboratory calibrated well chamber would be a suitable device to transfer an S(K)-based calibration to a clinical user. S(K) per well-chamber ionization current ratios were consistent among the four dots measured. Additionally, the measurements and predictions of anisotropy show uniform emission within the solid angle of the VAFAC, which demonstrates the robustness of the S(K) measurement approach. This characterization of a new (103)Pd directional brachytherapy source helps to establish calibration methods that could ultimately be used in the well-established AAPM Task Group 43 formalism. Monte Carlo methods accurately predict the changes in the energy spectrum caused by the fluorescent x-rays produced in the gold shield.

Air-kerma strength determination of a new directional 103Pd source

PubMed Central

Reed, Joshua L.; DeWerd, Larry A.; Culberson, Wesley S.

2015-01-01

Purpose: A new directional 103Pd planar source array called a CivaSheet™ has been developed by CivaTech Oncology, Inc., for potential use in low-dose-rate (LDR) brachytherapy treatments. The array consists of multiple individual polymer capsules called CivaDots, containing 103Pd and a gold shield that attenuates the radiation on one side, thus defining a hot and cold side. This novel source requires new methods to establish a source strength metric. The presence of gold material in such close proximity to the active 103Pd region causes the source spectrum to be significantly different than the energy spectra of seeds normally used in LDR brachytherapy treatments. In this investigation, the authors perform air-kerma strength (SK) measurements, develop new correction factors for these measurements based on an experimentally verified energy spectrum, and test the robustness of transferring SK to a well-type ionization chamber. Methods: SK measurements were performed with the variable-aperture free-air chamber (VAFAC) at the University of Wisconsin Medical Radiation Research Center. Subsequent measurements were then performed in a well-type ionization chamber. To realize the quantity SK from a directional source with gold material present, new methods and correction factors were considered. Updated correction factors were calculated using the mcnp 6 Monte Carlo code in order to determine SK with the presence of gold fluorescent energy lines. In addition to SK measurements, a low-energy high-purity germanium (HPGe) detector was used to experimentally verify the calculated spectrum, a sodium iodide (NaI) scintillating counter was used to verify the azimuthal and polar anisotropy, and a well-type ionization chamber was used to test the feasibility of disseminating SK values for a directional source within a cylindrically symmetric measurement volume. Results: The UW VAFAC was successfully used to measure the SK of four CivaDots with reproducibilities within 0.3%. Monte Carlo methods were used to calculate the UW VAFAC correction factors and the calculated spectrum emitted from a CivaDot was experimentally verified with HPGe detector measurements. The well-type ionization chamber showed minimal variation in response (<1.5%) as a function of source positioning angle, indicating that an American Association of Physicists in Medicine (AAPM) Accredited Dosimetry Calibration Laboratory calibrated well chamber would be a suitable device to transfer an SK-based calibration to a clinical user. SK per well-chamber ionization current ratios were consistent among the four dots measured. Additionally, the measurements and predictions of anisotropy show uniform emission within the solid angle of the VAFAC, which demonstrates the robustness of the SK measurement approach. Conclusions: This characterization of a new 103Pd directional brachytherapy source helps to establish calibration methods that could ultimately be used in the well-established AAPM Task Group 43 formalism. Monte Carlo methods accurately predict the changes in the energy spectrum caused by the fluorescent x-rays produced in the gold shield. PMID:26632069

A multicentric, international matched pair analysis of body composition in peritoneal dialysis versus haemodialysis patients.

PubMed

van Biesen, Wim; Claes, Kathleen; Covic, Adrian; Fan, Stanley; Lichodziejewska-Niemierko, Monika; Schoder, Volker; Verger, Christian; Wabel, Peter

2013-10-01

Volume status, lean and fat tissue are gaining interest as prognostic predictors in patients on dialysis. Comparative data in peritoneal dialysis (PD) versus haemodialysis (HD) patients are lacking. In a cohort of PD (EuroBCM) and HD (Euclid database) patients, matched for country, gender, age and dialysis vintage, body composition was assessed by bioimpedance spectroscopy (BCM, Fresenius Medical Care). Time-averaged volume overload (TAVO) was defined as the mean of pre- and post-dialysis volume overload (VO), and relative (%) (TA)VO as (TA)VO/ECV. Four hundred and ninety-one matched pairs (55.2% males, median age 60.0 years) were included. The body mass index (BMI, PD = 26.5 ± 4.7 versus HD = 25.9 ± 4.6 kg/m(2), P = 0.18 in males and 27.4 ± 5.8 versus 27.5 ± 6.6 kg/m(2), P = 0.75 in females) and fat tissue index (males: 11.5 ± 5.3 versus 11.4 ± 5.4 kg/m(2), P = 0.90, females: 14.8 ± 6.7 versus 15.4 ± 7.2 kg/m(2), P = 0.30) were not different in PD versus HD patients, whereas the lean tissue index (LTI) was higher in PD versus HD patients (males: 14.5 ± 3.4 versus 13.7 ± 3.1 kg/m(2), P = 0.001, females: 12.6 ± 3.3 versus 11.5 ± 2.6 kg/m(2), P < 0.0001). VO/extracellular water (ECW) was not different between PD versus just before the HD treatment (males: 10.8 ± 12.1 versus 9.2 ± 10.2%, P = 0.09; females: 6.5 ± 10.8 versus 7.7 ± 9.4%, P = 0.19). The relative TAVO was higher in PD versus HD (10.8 ± 12.1% versus 3.2 ± 11.2%, and 6.5 ± 10.8% versus 1.2 ± 10.9%, both P < 0.0001). The LTI was impaired, and this was more in males versus females, but was better preserved on PD versus HD, whereas fat tissue index (FTI) was increased, but not different between PD and HD. Volume overload was more present in PD versus HD when TAVO, but not when predialysis volume status, was used as a reference.

KSC-08pd3698

NASA Image and Video Library

2008-11-14

CAPE CANAVERAL, Fla. – Center Director Bob Cabana (center) shares a happy moment in the Firing Room of the Launch Control Center at NASA's Kennedy Space Center in Florida after the successful launch of space shuttle Endeavour on the STS-126 mission. Liftoff was on time at 7:55 p.m. EST. STS-126 is the 124th space shuttle flight and the 27th flight to the International Space Station. The mission will feature four spacewalks and work that will prepare the space station to house six crew members for long-duration missions. Photo credit: NASA/Kim Shiflett

KSC-08pd3723

NASA Image and Video Library

2008-11-14

CAPE CANAVERAL, Fla. – Atop twin towers of flame, space shuttle Endeavour races past the lightning mast on Launch Pad 39A at NASA's Kennedy Space Center in Florida, heading into space on the STS-126 mission. Liftoff was on time at 7:55 p.m. EST. STS-126 is the 124th space shuttle flight and the 27th flight to the International Space Station. The mission will feature four spacewalks and work that will prepare the space station to house six crew members for long-duration missions. Photo courtesy of Scott Andrews

Design and synthesis of 1-(benzothiazol-5-yl)-1H-1,2,4-triazol-5-ones as protoporphyrinogen oxidase inhibitors.

PubMed

Zuo, Yang; Yang, Sheng-Gang; Luo, Yan-Ping; Tan, Ying; Hao, Ge-Fei; Wu, Qiong-You; Xi, Zhen; Yang, Guang-Fu

2013-06-01

Protoporphyrinogen oxidase (PPO, E.C. 1.3.3.4) is the action target for several structurally diverse herbicides. A series of novel 4-(difluoromethyl)-1-(6-halo-2-substituted-benzothiazol-5-yl)-3-methyl-1H-1,2,4-triazol-5(4H)-ones 2a-z were designed and synthesized via the ring-closure of two ortho-substituents. The in vitro bioassay results indicated that the 26 newly synthesized compounds exhibited good PPO inhibition effects with K(i) values ranging from 0.06 to 17.79 μM. Compound 2e, ethyl 2-{[5-(4-(difluoromethyl)-3-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-6-fluorobenzo-thiazol-2-yl]thio}acetate, was the most potent inhibitor with K(i) value of 0.06 μM against mtPPO, comparable to (K(i)=0.03 μM) sulfentrazone. Further green house assays showed that compound 2f (K(i)=0.24 μM, mtPPO), ethyl 2-{[5-(4-(difluoromethyl)-3-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-6-fluorobenzothiazol-2-yl]thio}propanoate, showed the most promising post-emergence herbicidal activity with broad spectrum even at concentrations as low as 37.5 gai/ha. Soybean exhibited tolerance to compound 2f at the dosages of 150 gai/ha, whereas they are susceptible to sulfentrazone even at 75 gai/ha. Thus, compound 2f might be a potential candidate as a new herbicide for soybean fields. Copyright © 2013 Elsevier Ltd. All rights reserved.

Technetium-99m diethylenetriaminepentaacetic acid radioaerosol scintigraphy in organophosphate induced pulmonary toxicity: experimental study.

PubMed

Yavuz, Yucel; Kaya, Eser; Yurumez, Yusuf; Sahin, Onder; Bas, Orhan; Fidan, Huseyin; Sezer, Murat

2008-09-01

The aim of this experimental study was to investigate pathological signs of lung damages caused by acute organophosphate (OP) poisoning by using Tc-99m DTPA radioaerosol scintigraphy and histopathological investigation. Fourteen rabbits were divided into two equal groups (n = 7). Group 1 (control group) received normal saline (same volume of fenthion, 2 ml/kg) via orogastric tube. Group 2 (OP toxicity group) received 150 mg/kg of fenthion (diluted fenthion, 2 ml/kg) via orogastric tube. Six hours later, Tc-99m-DTPA aerosol inhalation lung scintigraphy was performed in both groups. Then all rabbits were anesthetized with ketamine hydrochloride (35 mg/kg, i.p.) and xysilazine (5 mg/kg, i.p.), and sacrificed by intracardiac blood discharge. The lungs were then removed. There was a significant difference in T1/2 values of Tc-99m DTPA clearance between control group and OP toxicity group (p = 0.04). Intraparenchymal vascular congestion and thrombosis, intraparenchymal hemorrhage, respiratory epithelial proliferation, number of macrophages in the alveolar, and bronchial lumen, alveolar destruction, emphysematous changes, and bronchoalveolar hemorrhage scores were significantly higher in the rabbits exposed to OP compared with the control group (p < 0.05). This study showed that OP toxicity caused a decrease in the alveolar clearance. Tc-99m DTPA radioaerosol inhalation lung scintigraphy was found to be a sensitive determination of acute lung damage in OP poisoning.

Glucose-6-phosphate dehydrogenase is a regulator of vascular smooth muscle contraction.

PubMed

Gupte, Rakhee S; Ata, Hirotaka; Rawat, Dhawjbahadur; Abe, Madoka; Taylor, Mark S; Ochi, Rikuo; Gupte, Sachin A

2011-02-15

Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in the pentose phosphate pathway and a major source of nicotinamide adenine dinucleotide phosphate reduced (NADPH), which regulates numerous enzymatic (including glutathione reductase and NADPH oxidase that, respectively, generates reduced glutathione and reactive oxygen species) reactions involved in various cellular actions, yet its physiological function is seldom investigated. We, however, recently showed that inhibiting G6PD causes precontracted coronary artery (CA) to relax in an endothelium-derived relaxing factor- and second messenger-independent manner. Here we assessed the role of G6PD in regulating CA contractility. Treating bovine CAs for 20 min with potassium chloride (KCl; 30 mM), amphotericin B (50 μM), or U46619 (100 nM) significantly (p < 0.05) increased both G6PD activity and glucose flux through the pentose phosphate pathway. The effect was Ca(2+) independent, and there was a corresponding increase in protein kinase C (PKC) activity. Activation of G6PD by KCl was blocked by the PKCδ inhibitor rottlerin (10 μM) or by knocking down PKCδ expression using siRNA. Phorbol 12, 13-dibutyrate (10 μM), a PKC activator, significantly increased G6PD phosphorylation and activity, whereas single (S210A, T266A) and double (S210A/T266A) mutations at sites flanking the G6PD active site significantly inhibited phosphorylation, shifted the isoelectric point, and reduced enzyme activity. Knocking down G6PD decreased NADPH and reactive oxygen species generation, and reduced KCl-evoked increases in [Ca(2+)](i) and myosin light chain phosphorylation, thereby reducing CA contractility. Similarly, aortas from G6PD-deficient mice developed less KCl/phorbol 12, 13-dibutyrate-evoked force than those from their wild-type littermates. Conversely, overexpression of G6PD augmented KCl-evoked increases in [Ca(2+)](i), thereby augmenting CA contraction. Our findings demonstrate that G6PD activity and NADPH is increased in activated CA in a PKCδ-dependent manner and that G6PD modulates Ca(2+) entry and CA contractions evoked by membrane depolarization.

Association of hyperfunctioning thyroid adenoma with thyroid cancer presenting as "trapping only" nodule at 99mTcO4- scintigraphy.

PubMed

dell'Erba, L; Gerundini, P; Caputo, M; Bagnasco, M

2003-11-01

Rarely may a non-hyperfunctioning thyroid nodule present as "hot" at Technetium-99m pertechnetate (99mTcO4-) and "cold" at radioiodine scintigraphy at late acquisitions. We report the case of a hyperthyroid female patient whose 99mTcO4- scintigraphy showed two "hot" nodules, whereas Iodide-131 (131I-) revealed a lack of indicator uptake by the larger, and intense uptake by the smaller nodule. The patient underwent surgery: histology demonstrated that the larger nodule, mismatched at pertechnetate vs iodine scintigraphy, was a papillary carcinoma. Our suggestion is to perform thyroid scintigraphy with radioiodine in hyperthyroid patients with more than one nodule concentrating pertechnetate, especially when an ultrasonographic pattern possibly suspect for malignancy is present.

Efficacy of statin delivery as an adjunct to scaling and root planing in the treatment of chronic periodontitis: A meta-analysis.

PubMed

Akram, Zohaib; Vohra, Fahim; Javed, Fawad

2018-05-01

The action of statins in stimulating bone formation and having other pleiotropic effects, such as anti-inflammatory and immunomodulatory effects, has justified their use as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis (CP). The aim of the present study was to evaluate the efficacy of statin delivery as an adjunct to SRP in the treatment of CP. Electronic searches were conducted using the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Oral Health Group Trials Register, up until July 2017. The primary outcome was probing depth (PD), while the secondary outcomes were changes in clinical attachment level (CAL) and bone defect (BD) fill. Eleven studies were included, and all showed significant PD reduction, CAL gain, and BD fill with adjunctive statin delivery compared to SRP alone. The meta-analysis showed significant improvement in periodontal parameters for atorvastatin (PD: weighted mean difference [WMD] = -1.84, -2.56 to -1.12, P < .001; CAL: WMD = -2.31, -3.58 to -1.03, P < .001; BD fill: WMD = 2.66, -3.92 to -1.39, P < .001), simvastatin (PD: WMD = -1.91, -2.27 to -1.55, P < .001; CAL: WMD = -1.91, -2.27 to -1.55, P = .001; BD: WMD = -1.52, -2.20 to -0.85, P < .001), and rosuvastatin (PD: WMD = -0.94, -1.32 to -0.55, P < .001; CAL: WMD = -1.00, -1.41 to -0.60, P < .001; BD fill: WMD = -1.30, -1.80 to -0.79, P < .001). Adjunctive statin delivery appears to be effective in reducing PD, CAL gain, and BD fill in CP, and therefore, these drugs could be a promising therapeutic option for periodontal regeneration in future. © 2017 John Wiley & Sons Australia, Ltd.

Usefulness of rCBF analysis in diagnosing Parkinson's disease: supplemental role with MIBG myocardial scintigraphy.

PubMed

Nagamachi, Shigeki; Wakamatsu, Hideyuki; Kiyohara, Shogo; Fujita, Seigo; Futami, Shigemi; Tamura, Shozo; Nakazato, Masamitsu; Yamashita, Syuichi; Arita, Hideo; Nishii, Ryuichi; Kawai, Keiichi

2008-08-01

(123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is a useful tool for differentiating idiopathic Parkinson's disease (PD) from parkinsonism (PS) caused by other disorders. However, cardiac MIBG uptake is affected by various causes. Alternatively, hypoperfusion in the occipital lobe of PD is reported recently. The objective is to clarify the correlation between regional cerebral blood flow (rCBF) alteration and cardiac MIBG uptake in PD. In addition, we examined whether additional brain perfusion analysis improved the differential diagnostic ability for PD from PS when compared with MIBG scintigraphy alone. Forty-nine patients with PD (27 mild groups: Hoehn and Yahr stages I, II; 22 severe groups: Hoehn and Yahr stages III, IV) and 28 patients with PS participated. We compared absolute rCBF values between PD and PS. In addition, we determined correlation between MIBG parameters and each rCBF value. Finally, we compared the diagnostic ability for the differentiation of PD from PS between two diagnostic criteria, each MIBG index abnormality alone [heart-to-mediastinum ratio, H/M (E) < 1.9, H/E (D) < 1.7, washout rate > 40%] and each MIBG index abnormality or occipital lobe hypoperfusion (<36 ml/100 g per min). Absolute rCBF value of occipital lobe was significantly lower in severe PD as compared with PS or mild PD. In the correlation analysis, rCBF of occipital lobe correlated positively with MIBG parameters (H/M). Regarding the diagnostic ability, sensitivity improved by accounting for occipital hypoperfusion as compared with MIBG indices alone. In contrast, neither specificity nor accuracy improved by adding occipital lobe analysis. MIBG parameters (H/M) correlated positively with occipital hypoperfusion in PD. In the differential diagnosis between PD and PS, although its usefulness might be limited, analysis of rCBF in the occipital lobe added to (123)I-MIBG myocardial imaging can be recommended.

KSC-08pd1113

NASA Image and Video Library

2008-05-03

CAPE CANAVERAL, Fla. -- At NASA's Kennedy Space Center, the rotating service structure, at left, at Launch Pad 39A has been rolled back for the delivery of space shuttle Discovery, secured atop the mobile launch platform below, for final prelaunch processing for the STS-124 mission. The 3.4-mile journey from the Vehicle Assembly Building began at 11:47 p.m. on May 2. The shuttle arrived at the launch pad at 4:25 a.m. EDT May 3 and was secured, or hard down, by 6:06 a.m. On the 13-day mission, Discovery and its crew will deliver the Japan Aerospace Exploration Agency's Japanese Experiment Module – Pressurized Module and the Japanese Remote Manipulator System. Launch is targeted for May 31. Photo credit: NASA/Troy Cryder

KSC-08pd1101

NASA Image and Video Library

2008-05-03

CAPE CANAVERAL, Fla. -- At NASA's Kennedy Space Center, a crawler transporter moves space shuttle Discovery, secured atop a mobile launch platform, along the crawlerway from the Vehicle Assembly Building to Launch Pad 39A to prepare for the STS-124 mission. The 3.4-mile journey from the Vehicle Assembly Building began at 11:47 p.m. on May 2. The shuttle arrived at the launch pad at 4:25 a.m. EDT May 3 and was secured, or hard down, by 6:06 a.m. On the 13-day mission, Discovery and its crew will deliver the Japan Aerospace Exploration Agency's Japanese Experiment Module – Pressurized Module and the Japanese Remote Manipulator System. Launch is targeted for May 31. Photo credit: NASA/Troy Cryder

KSC-08pd1111

NASA Image and Video Library

2008-05-03

CAPE CANAVERAL, Fla. -- At NASA's Kennedy Space Center, access arms from the fixed service structure at Launch Pad 39A are in place against space shuttle Discovery, secured atop the mobile launch platform below, as final prelaunch processing for the STS-124 mission begins at the pad. The 3.4-mile journey from the Vehicle Assembly Building began at 11:47 p.m. on May 2. The shuttle arrived at the launch pad at 4:25 a.m. EDT May 3 and was secured, or hard down, by 6:06 a.m. On the 13-day mission, Discovery and its crew will deliver the Japan Aerospace Exploration Agency's Japanese Experiment Module – Pressurized Module and the Japanese Remote Manipulator System. Launch is targeted for May 31. Photo credit: NASA/Troy Cryder

KSC-08pd1108

NASA Image and Video Library

2008-05-03

CAPE CANAVERAL, Fla. -- At Launch Pad 39A at NASA's Kennedy Space Center, the payload for the STS-124 mission, secured in the payload changeout room on the rotating service structure, at left, awaits installation into the payload bay of space shuttle Discovery. Discovery's 3.4-mile journey from the Vehicle Assembly Building began at 11:47 p.m. on May 2. The shuttle arrived at the launch pad at 4:25 a.m. EDT May 3 and was secured, or hard down, by 6:06 a.m. On the 13-day mission, Discovery and its crew will deliver the Japan Aerospace Exploration Agency's Japanese Experiment Module – Pressurized Module and the Japanese Remote Manipulator System. Launch is targeted for May 31. Photo credit: NASA/Troy Cryder

KSC-08pd1102

NASA Image and Video Library

2008-05-03

CAPE CANAVERAL, Fla. -- At NASA's Kennedy Space Center, space shuttle Discovery, secured atop a mobile launch platform, is reflected in water beside the crawlerway as it is moved from the Vehicle Assembly Building to Launch Pad 39A to prepare for the STS-124 mission. The 3.4-mile journey from the Vehicle Assembly Building began at 11:47 p.m. on May 2. The shuttle arrived at the launch pad at 4:25 a.m. EDT May 3 and was secured, or hard down, by 6:06 a.m. On the 13-day mission, Discovery and its crew will deliver the Japan Aerospace Exploration Agency's Japanese Experiment Module – Pressurized Module and the Japanese Remote Manipulator System. Launch is targeted for May 31. Photo credit: NASA/Troy Cryder

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

Thorstad, B.L.; Russell, C.D.; Dubovsky, E.V.

A case of renovascular hypertension is presented in which the (/sup 131/I)hippuran renogram was initially normal, but became strikingly abnormal upon administration of the angiotensin converting enzyme (ACE) inhibitor captopril. The patient presented with fibromuscular dysplasia of the renal arteries, which was shown by hippuran renography to be functionally significant on the right side. She became normotensive after angioplasty of the right renal artery. Hypertension recurred a year later, at which time the renogram was normal without captopril, but showed functionally significant left renal artery stenosis with captopril challenge. Both the conventional agent, (/sup 131/I)hippuran, and an experimental new /supmore » 99m/Tc-labeled hippuran analog, (/sup 99m/Tc)MAG3, were used. Angiography confirmed progression of disease on the left side, which was successfully treated by angioplasty. Functionally significant unilateral renal artery stenosis was thus demonstrated first on the right side and then, 1 yr later, on the left side, using hippuran and (/sup 99m/Tc)MAG3. Anatomic progression of disease was documented by angiography.« less

Hypotensive and vasorelaxant effects of citronellol, a monoterpene alcohol, in rats.

PubMed

Bastos, Joana F A; Moreira, Italo J A; Ribeiro, Thaís P; Medeiros, Isac A; Antoniolli, Angelo R; De Sousa, Damião P; Santos, Márcio R V

2010-04-01

Citronellol is an essential oil constituent from the medicinal plants Cymbopogon citratus, Cymbopogon winterianus and Lippia alba which are thought to possess antihypertensive properties. Citronellol-induced cardiovascular effects were evaluated in this study. In rats, citronellol (1-20 mg/kg, i.v.) induced hypotension, which was not affected by pre-treatment with atropine, hexamethonium, N(omega)-nitro-L-arginine methyl ester hydrochloride or indomethacin, and tachycardia, which was only attenuated by pre-treatment with atropine and hexamethonium. These responses were less than those obtained for nifedipine, a reference drug. In intact rings of rat mesenteric artery pre-contracted with 10 microM phenylephrine, citronellol induced relaxations (pD(2) = 0.71 +/- 0.11; E(max) = 102 +/- 5%; n = 6) that were not affected by endothelium removal, after tetraethylamonium in rings without endothelium pre-contracted with KCl 80 mM. Citronellol strongly antagonized (maximal inhibition = 97 +/- 4%; n = 6) the contractions induced by CaCl(2) (10(-6) to 3 x 10(-3 )M) and did not induce additional effects on the maximal response of nifedipine (10 microM). Finally, citronellol inhibited the contractions induced by 10 microM phenylephrine or 20 mM caffeine. The present results suggest that citronellol lowers blood pressure by a direct effect on the vascular smooth muscle leading to vasodilation.

Effective atomic numbers and electron densities of some human tissues and dosimetric materials for mean energies of various radiation sources relevant to radiotherapy and medical applications

NASA Astrophysics Data System (ADS)

Kurudirek, Murat

2014-09-01

Effective atomic numbers, Zeff, and electron densities, neff, are convenient parameters used to characterise the radiation response of a multi-element material in many technical and medical applications. Accurate values of these physical parameters provide essential data in medical physics. In the present study, the effective atomic numbers and electron densities have been calculated for some human tissues and dosimetric materials such as Adipose Tissue (ICRU-44), Bone Cortical (ICRU-44), Brain Grey/White Matter (ICRU-44), Breast Tissue (ICRU-44), Lung Tissue (ICRU-44), Soft Tissue (ICRU-44), LiF TLD-100H, TLD-100, Water, Borosilicate Glass, PAG (Gel Dosimeter), Fricke (Gel Dosimeter) and OSL (Aluminium Oxide) using mean photon energies, Em, of various radiation sources. The used radiation sources are Pd-103, Tc-99, Ra-226, I-131, Ir-192, Co-60, 30 kVp, 40 kVp, 50 kVp (Intrabeam, Carl Zeiss Meditec) and 6 MV (Mohan-6 MV) sources. The Em values were then used to calculate Zeff and neff of the tissues and dosimetric materials for various radiation sources. Different calculation methods for Zeff such as the direct method, the interpolation method and Auto-Zeff computer program were used and agreements and disagreements between the used methods have been presented and discussed. It has been observed that at higher Em values agreement is quite satisfactory (Dif.<5%) between the adopted methods.

40 CFR 94.103 - Test procedures for Category 1 marine engines.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Test procedures for Category 1 marine... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM MARINE COMPRESSION-IGNITION ENGINES Test Procedures § 94.103 Test procedures for Category 1 marine engines. (a) Gaseous and particulate emissions shall be measured...

40 CFR 94.103 - Test procedures for Category 1 marine engines.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Test procedures for Category 1 marine... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM MARINE COMPRESSION-IGNITION ENGINES Test Procedures § 94.103 Test procedures for Category 1 marine engines. (a) Gaseous and particulate emissions shall be measured...

Insights into the intramolecular donor stabilisation of organostannylene palladium and platinum complexes: syntheses, structures and DFT calculations.

PubMed

Wagner, Michael; Deáky, Vajk; Dietz, Christina; Martincová, Jana; Mahieu, Bernard; Jambor, Roman; Herres-Pawlis, Sonja; Jurkschat, Klaus

2013-05-17

The syntheses of the transition metal complexes cis-[(4-tBu-2,6-{P(O)(OiPr)2}2C6H2SnCl)2MX2] (1, M = Pd, X = Cl; 2, M = Pd, X = Br; 3, M = Pd, X = I; 4, M = Pt, X = Cl), cis-[{2,6-(Me2NCH2)2C6H3SnCl}2MX2] (5, M = Pd, X = I; 6, M = Pt, X = Cl), trans-[{2,6-(Me2NCH2)2C6H3SnI}2PtI2] (7) and trans-[(4-tBu-2,6-{P(O)(OiPr)2}2C6H2SnCl)PdI2]2 (8) are reported. Also reported is the serendipitous formation of the unprecedented complexes trans-[(4-tBu-2,6-{P(O)(OiPr)2}2C6H2SnCl)2Pt(SnCl3)2] (10) and [(4-tBu-2,6-{P(O)(OiPr)2}2C6H2SnCl)3Pt(SnCl3)2] (11). The compounds were characterised by elemental analyses, (1)H, (13)C, (31)P, (119)Sn and (195)Pt NMR spectroscopy, single-crystal X-ray diffraction analysis, UV/Vis spectroscopy and, in the cases of compounds 1, 3 and 4, also by Mössbauer spectroscopy. All the compounds show the tin atoms in a distorted trigonal-bipyramidal environment. The Mössbauer spectra suggest the tin atoms to be present in the oxidation state III. The kinetic lability of the complexes was studied by redistribution reactions between compounds 1 and 3 as well as between 1 and cis-[{2,6-(Me2 NCH2)2C6H3SnCl}2PdCl2]. DFT calculations provided insights into both the bonding situation of the compounds and the energy difference between the cis and trans isomers. The latter is influenced by the donor strength of the pincer-type ligands. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and comparative in vivo evaluation of 99m Tc(CO)3 -labeled PEGylated and non-PEGylated cRGDfK peptide monomers.

PubMed

Vats, Kusum; Satpati, Drishty; Sharma, Rohit; Sarma, Haladhar D; Banerjee, Sharmila

2017-03-01

This work aimed at studying the effect of insertion of medium PEG (PEG 7 ) on the pharmacokinetic behavior of cRGDfK peptide in comparison with the non-PEGylated analogue. The cRGDfK peptide has thus been derivatized at ε-amino group of lysine by conjugation with N 3 -PEG 7 -COOH/N 3 -CH 2 -COOH to prepare a PEGylated and a non-PEGylated analogue of cRGDfK. A tridentate chelator was then incorporated by click chemistry conjugation of the two peptide azides for radiolabeling with [ 99m Tc(CO) 3 (H 2 O) 3 ] + precursor. Comparative in vivo evaluation of the two 99m Tc(CO) 3 -labeled radiotracers, 99m Tc(CO) 3 -Pra-Tz-CH 2 -cRGDfK 5 and 99m Tc(CO) 3 -Pra-Tz-PEG 7 -cRGDfK 6, was carried out in C57BL/6 mice bearing α v β 3 -positive melanoma tumors to determine their potential toward targeting integrin α v β 3 receptors. The radiotracers exhibited excellent stability in saline as well as in serum. Maximum tumor uptake for the two radiotracers was observed at 30 min p.i. (5: 3.0 ± 0.7% ID/g; 6: 4.1 ± 0.5% ID/g). The two neutral 99m Tc(CO) 3 radiotracers prepared exhibited receptor-mediated uptake in melanoma tumor. The increase in the tumor uptake on introduction of PEG 7 unit was accompanied by slower clearance from other organs which resulted in decreased target-to-background ratios. The in vivo kinetics of 99m Tc(CO) 3 -labeled radiotracer, 99m Tc(CO) 3 -Pra-Tz-CH 2 -cRGDfK 5 with only methylene unit as the spacer, was found to be more favorable due to higher tumor/blood, tumor/liver, tumor/kidney, and tumor/lung ratios. © 2016 John Wiley & Sons A/S.

The MicroRNA miR-124 Promotes Neuronal Differentiation by Triggering Brain-Specific Alternative Pre-mRNA Splicing

PubMed Central

Makeyev, Eugene V.; Zhang, Jiangwen; Carrasco, Monica A.; Maniatis, Tom

2011-01-01

SUMMARY Both microRNAs and alternative pre-mRNA splicing have been implicated in the development of the nervous system (NS), but functional interactions between these two pathways are poorly understood. We demonstrate that the neuron-specific microRNA miR-124 directly targets PTBP1 (PTB/hnRNP I) mRNA, which encodes a global repressor of alternative pre-mRNA splicing in nonneuronal cells. Among the targets of PTBP1 is a critical cassette exon in the pre-mRNA of PTBP2 (nPTB/brPTB/PTBLP), an NS-enriched PTBP1 homolog. When this exon is skipped, PTBP2 mRNA is subject to nonsense-mediated decay (NMD). During neuronal differentiation, miR-124 reduces PTBP1 levels, leading to the accumulation of correctly spliced PTBP2 mRNA and a dramatic increase in PTBP2 protein. These events culminate in the transition from non-NS to NS-specific alternative splicing patterns. We also present evidence that miR-124 plays a key role in the differentiation of progenitor cells to mature neurons. Thus, miR-124 promotes NS development, at least in part by regulating an intricate network of NS-specific alternative splicing. PMID:17679093

Pharmacokinetic and Pharmacodynamic Evaluation of Marbofloxacin in Pig against Korean Local Isolates of Actinobacillus pleuropneumoniae.

PubMed

Hossain, Md Akil; Park, Hae-Chul; Jeong, Kyunghun; Jang, Yang Ho; Kim, Dae Gyun; Kang, JeongWoo; Lee, Kwang-Jick

2017-01-01

The pharmacokinetics of marbofloxacin in pigs after intravenous (i.v.), intramuscular (i.m.), and peroral (p.o.) administration and pharmacokinetic/pharmacodynamic indices of this drug against Korean local isolates of Actinobacillus pleuropneumoniae were determined in this study. Marbofloxacin (2.50 mg/kg of body weight) was administered, and blood samples were collected with designated time intervals. Plasma-extracted marbofloxacin was injected into the LC-MS/MS system. The in vitro and ex vivo antibacterial activities of marbofloxacin were evaluated against 20 isolates of A. pleuropneumoniae . The mean peak plasma concentrations ( C max ) after i.v., i.m., and p.o administration were 2.60 ± 0.10, 2.59 ± 0.12, and 2.34 ± 0.12  µ g/mL at 0.25 ± 0.00, 0.44 ± 0.10, and 1.58 ± 0.40 h, respectively. The area under the plasma concentration-time curves (AUC 0-24 ) and elimination half-lives were 24.80 ± 0.90, 25.80 ± 1.40, and 23.40 ± 5.00 h· μ g/mL and 8.60 ± 0.30, 12.80 ± 1.10, and 8.60 ± 0.00 h, for i.v., i.m., and p.o. administration, correspondingly. The AUC 0-24 /MICs of marbofloxacin after i.v., i.m., and p.o. administration were 253.86 ± 179.91, 264.1 ± 187.16, and 239.53 ± 169.75 h, respectively. The C max /MIC values were 26.58 ± 18.84, 26.48 ± 18.77, and 23.94 ± 16.97, and T>MICs were 42.80 ± 1.01, 36.40 ± 1.24, and 38.60 ± 1.18 h, after i.v., i.m., and p.o. administration, respectively. Thus, marbofloxacin dosage of 2.50 mg/kg of body weight by i.v., i.m., and p.o. administration with 24 h dosing interval will provide effective treatment for the infection of pig by A. pleuropneumonia .

Hyperfunctioning parathyroid tumours in patients with thyroid nodules. Sensitivity and positive predictive value of high-resolution ultrasonography and 99mTc-sestamibi scintigraphy.

PubMed

Lumachi, F; Marzola, M C; Zucchetta, P; Tregnaghi, A; Cecchin, D; Bui, F

2003-09-01

A series of 112 consecutive patients with primary hyperparathyroidism who underwent both high-resolution neck ultrasonography (US) and 99mTc-sestamibi/99mTc-pertechnetate subtraction scintigraphy (SS) prior to successful parathyroidectomy was reviewed. There were 29 (25.9%) men and 83 (74.1%) women, with a median age of 58 years (range 13-78 years). Patients were divided into two groups, according to the preoperative US findings: group A (87 patients, 77.7%) without thyroid diseases, and group B (25 patients, 22.3%) with either multinodular goitre or a solitary nontoxic thyroid nodule. In group B patients partial or total thyroidectomy was also performed, according to the intraoperative findings and frozen-section examination results. Final histopathology showed 99 (88.4%) solitary parathyroid (PT) adenomas and 3 (2.7%) PT carcinomas, while 10 (8.9%) patients had a multiglandular disease. The sensitivity and positive predictive value (PPV) were (group A vs group B) 79.8% vs 70.8% (P=0.25) and 95.7% vs 94.4% (P=0.58) for US, and 83.3% vs 87.0% (P=0.47) and 95.9% vs 90.9% (P=0.32) for SS respectively. Better but similar (P=not significant) results were obtained in patients with solitary PT tumours: 81.5% vs 77.8% (US) and 85.0 vs 94.1% (SS) sensitivity; 97.1% vs 93.3% (US) and 95.8% vs 88.9% (SS) PPV. Overall, the combination of US and SS was 92.9% sensitive (group A=93.1%, group B=92.0%; P=0.55), and the PPV reached 100% in each group. In conclusion, in patients with primary hyperparathyroidism the results of both US and SS are independent of coexistent thyroid disease, especially in patients with solitary PT tumours.

Screening for Hepatopulmonary Syndrome in Cirrhotic Patients Using Technetium 99m-macroaggregated Albumin Perfusion Lung Scan (Tc-MAA): Diagnostic Approach and Clinical Correlations.

PubMed

Fragaki, Maria; Sifaki-Pistolla, Dimitra; Samonakis, Dimitrios N; Koulentaki, Mairi; Koukouraki, Sofia; Stathaki, Maria; Kouroumalis, Elias

2017-09-28

The aims of this study were to prospectively screen cirrhotic patients with arterial blood gas test and albumin perfusion scan, identify those fulfilling the classic hepatopulmonary syndrome (HPS) criteria, correlate with clinical parameters, and evaluate the survival of patients with HPS compared with those without HPS in a genetically homogenous Cretan cirrhotic population. Data on consecutive 102 patients within 1 year were collected and analyzed. All patients underwent a technetium 99m-macroaggregated albumin perfusion lung scan (Tc-MAA). Diagnosis of HPS was based on the presence of the quantitative index Tc-MAA≥6% and a [P(A-a)O2]≥15 mm Hg (≥20 mm Hg for patients over >64 y). In 94/102 patients, complete scintigraphic data were available. In total, 24 (26%) patients fulfilled the diagnostic criteria of HPS; 95.8% of them had mild-to-moderate HPS. In 8 patients the Tc-MAA scintigraphy could not be interpreted. There was no difference in HPS between decompensated (24.6%) and compensated cirrhosis (27.3%). In the multivariate analysis only the quantitative index was significant for the diagnosis of HPS (P=0.001, odds ratio; 95% confidence interval, 7.05; 2.27-21.87). Kaplan- Meier survival curves indicated a similar overall prognosis for patients diagnosed with HPS (P=0.105). HPS is a frequent complication of cirrhosis. Mild-to-moderate HPS has no significant effect on survival of cirrhotic patients. The quantitative Tc-MAA test is a reliable tool for diagnosis.

Novel 99mTc(III)-azide complexes [99mTc(N3)(CDO)(CDOH)2B-R] (CDOH2=cyclohexanedione dioxime) as potential radiotracers for heart imaging.

PubMed

Liu, Min; Zheng, Yumin; Avcibasi, Ugur; Liu, Shuang

2016-11-01

In this study, novel 99m Tc(III)-azide complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R] ( 99m Tc-ISboroxime-N 3 : R=IS; 99m Tc-MPboroxime-N 3 : R=MP; 99m Tc-PAboroxime-N 3 : R=PA; 99m Tc-PYboroxime-N 3 : R=PY; and 99m Tc-Uboroxime-N 3 : R=5U) were evaluated as heart imaging agents. Complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R] (R=IS, MP, PA, PY and 5U) were prepared by ligand exchange between NaN 3 and [ 99m TcCl(CDO)(CDOH) 2 B-R]. Biodistribution and imaging studies were carried out in Sprague-Dawley rats. Image quantification was performed to compare their initial heart uptake and myocardial retention. 99m Tc-ISboroxime-N 3 , 99m Tc-PYboroxime-N 3 and 99m Tc-Uboroxime-N 3 were prepared with high RCP (93-98%) while the RCP of 99m Tc-MPboroxime-N 3 and 99m Tc-PAboroxime-N 3 was 80-85%. The myocardial retention curves of 99m Tc-ISboroxime-N 3 , 99m Tc-PYboroxime-N 3 and 99m Tc-Uboroxime-N 3 were best fitted to the bi-exponential decay function. The half-time of the fast component was 1.6±0.4min for 99m Tc-ISboroxime-N 3 , 0.7±0.1min for 99m Tc-PYboroxime-N 3 and 0.9±0.4min for 99m Tc-Uboroxime-N 3 . The 2-min heart uptake from biodistribution studies followed the ranking order of 99m Tc-ISboroxime-N 3 (3.60±0.68%ID/g)> 99m Tc-PYboroxime-N 3 (2.35±0.37%ID/g)≫ 99m Tc-Uboroxime-N 3 (1.29±0.06%ID/g). 99m Tc-ISboroxime-N 3 had the highest 2-min heart uptake among 99m Tc radiotracers revaluated in SD rats. High quality SPECT images were obtained with the right and left ventricular walls being clearly delineated. The best image acquisition window was 0-5min for 99m Tc-ISboroxime-N 3 . Both azide coligand and boronate caps had significant impact on the heart uptake and myocardial retention of complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R]. Among the radiotracers evaluated in SD rats, 99m Tc-ISboroxime-N 3 has the highest initial heart uptake with the heart retention comparable to that of 99m Tc-Teboroxime. 99m Tc-ISboroxime-N 3 is a promising alternative to 99m Tc-Teboroxime for SPECT MPI. Copyright © 2016 Elsevier Inc. All rights reserved.

Episodic weakness due to mitochondrial DNA MT-ATP6/8 mutations.

PubMed

Auré, Karine; Dubourg, Odile; Jardel, Claude; Clarysse, Lucie; Sternberg, Damien; Fournier, Emmanuel; Laforêt, Pascal; Streichenberger, Nathalie; Petiot, Philippe; Gervais-Bernard, Hélène; Vial, Christophe; Bedat-Millet, Anne-Laure; Drouin-Garraud, Valérie; Bouillaud, Frédéric; Vandier, Christophe; Fontaine, Bertrand; Lombès, Anne

2013-11-19

To report that homoplasmic deleterious mutations in the mitochondrial DNA MT-ATP6/8 genes may be responsible for acute episodes of limb weakness mimicking periodic paralysis due to channelopathies and dramatically responding to acetazolamide. Mitochondrial DNA sequencing and restriction PCR, oxidative phosphorylation functional assays, reactive oxygen species metabolism, and patch-clamp technique in cultured skin fibroblasts. Occurrence of a typical MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) syndrome in a single member of a large pedigree with episodic weakness associated with a later-onset distal motor neuropathy led to the disclosure of 2 deleterious mitochondrial DNA mutations. The MT-ATP6 m.9185T>C p.Leu220Pro mutation, previously associated with Leigh syndrome, was present in all family members, while the MT-TL1 m.3271T>C mutation, a known cause of MELAS syndrome, was observed in the sole patient with MELAS presentation. Significant defect of complexes V and I as well as oxidative stress were observed in both primary fibroblasts and cybrid cells with 100% m.9185T>C mutation. Permanent plasma membrane depolarization and altered permeability to K(+) in fibroblasts provided a link with the paralysis episodes. Screening of 9 patients, based on their clinical phenotype, identified 4 patients with similar deleterious MT-ATP6 mutations (twice m.9185T>C and once m.9176T>C or m.8893T>C). A fifth patient presented with an original potentially deleterious MT-ATP8 mutation (m.8403T>C). All mutations were associated with almost-normal complex V activity but significant oxidative stress and permanent plasma membrane depolarization. Homoplasmic mutations in the MT-ATP6/8 genes may cause episodic weakness responding to acetazolamide treatment.